3BIO-BioMatter Team Publications

Peer-reviewed journal articles

 

Articles dans des revues avec comité de lecture

2025

Potential Multi‐Functional Sprayable Poly(N‐Isopropylacrylamide)/Dextran Hydrogel Dressings With Incorporation of Silver Nanowires

ABSTRACT Smart polymer‐based hydrogels with properties such as temperature‐responsive performance, sprayability, antimicrobial effects, and antioxidant activity hold promise for wound dressing applications. In this study, aminated poly(N‐isopropylacrylamide) (PNIPAM‐NH 2 ) was synthesized via the free radical polymerization of N‐isopropylacrylamide (NIPAM), and dopamine‐grafted aldehyde dextran (Odex‐DA) was also prepared. A pre‐solution was then prepared by combining PNIPAM‐NH 2 , Odex‐DA, and silver nanowires (AgNWs) at room temperature conditions with its temperature‐responsive behaviour demonstrated by injecting the pre‐solution into the water at a temperature of 37°C leading to the transition of the OPAg pre‐solution to hydrogels. The obtained multi‐functional OPAg hydrogels exhibited an interconnected microstructure and injectability. In addition, the OPAg pre‐solution displayed sprayability, forming an adherent hydrogel layer on human skin upon application. Furthermore, the OPAg hydrogels exhibited strong antimicrobial ability against E. coli and S. aureus , along with favourable DPPH scavenging ability. Cytocompatibility was confirmed by CCK‐8 assays and fluorescence imaging with NIH‐3T3 cells. Overall, this study developed a multifunctional, sprayable hydrogel with strong potential for use in wound healing.

Borax - and tannic acid-based post-3D-printing treatment to tune the mechanical properties of scaffolds

Post-processing of DLP-printed polyethylene glycol diacrylate (PEGDA)/polyvinyl alcohol (PVA) resins with tannic acid (TA) enhanced their mechanical properties and introduced bioactive functionalities.

Unlocking synergies in low-temperature co-liquefaction of food residues for biocrude production: Experimental and simulation insights into food waste valorisation

Analysis of the Technical and Economic Viability of Upcycling Sustainable Fish Waste for Bioproduct Production

A critical review of ultrasonication as a green technology for enhanced biomass valorization in bioethanol and biogas production

Machine learning-based predictive modeling and optimization: Artificial neural network-genetic algorithm vs. response surface methodology for black soldier fly (Hermetia illucens) farm waste fermentation

Recognizing the complexity of non-linear and interdependent biological processes, this study compared the predictive performance of artificial neural network (ANN) models with response surface methodology regression based (RB) models. The research focused on the biological transformation of black soldier fly (Hermetia illucens) farm waste into chitin, facilitated by Lactobacillus paracasei. Key parameters of time (1-7 days), temperature (30-40 °C), substrate concentration (7.5-20 wt%), and inoculum concentration (5-15 v/v%), were evaluated for their impact on demineralization and deproteinization subprocesses and subsequently optimized. It was determined that the ANN models outperformed RB models, with R² values of 0.950 and 0.959 for DP% and DD%, compared to 0.677 and 0.720 for RB models. While both models, optimized using a multi-objective genetic algorithm (MOGA) and a desirability function respectively, produced comparable optimal results, differences emerged in process variable analysis. Main effects plots (RB) and one way partial dependence plots (ANN) revealed conflicting parameter influences, highlighting the limitations of regression models in complex systems. This study highlights the superiority of ANN-MOGA in addressing biological complexity and recommends its use especially if RB models show suboptimal predictive capabilities.

Enzyme-immobilized and fluorinated hydrogel for enhanced oxygen retention in hypoxia treatment

Nanozymes as catalysts for accelerated healing of diabetic wounds

Optimization of peroxidase-like activity of manganese-tannic acid complexes

Metal-phenolic networks (MPNs) have drawn widespread attention due to their facile synthesis process, favorable biocompatibility, and antimicrobial properties. The present study investigated an environmentally friendly method for synthesizing manganese-tannic acid (Mn-TA) complexes with peroxidase (POD) like properties. The research focuses on optimizing the yield and enzyme-mimetic activity of the Mn-TA complex. A ligand-to-metal charge transfer band at approximately 603 cm⁻¹ in the FTIR spectrum suggested that Mn-TA complexes had been successfully formed. The Box-Behnken Design (BBD) was employed to evaluate the influence of key variables, including pH (4-10), temperature (25-90 °C), the molar ratio of Mn2 + to TA (1:1-1:6), and reaction time (1-6 h), on the yield and enzyme-mimetic activity. Enzyme-mimetic activity was quantified using absorbance spectroscopy. The optimum yield and absorbance of the Mn-TA complex of 72.88 wt% and 0.694 AU, respectively, were achieved at the conditions of pH 10.0, temperature 43 °C, molar ratio of 1:1, and a reaction time of 6 h. The optimally produced Mn-TA complexes displayed a POD-like activity with an estimated Michaelis-Menten constant value of 0.481 mM. The study also showed Mn-TA complexes possess biocompatibility and have antibacterial activities.

The authors regret that the printed version of the above article contained an error in Fig 4a. The correct and final version follows. The authors would like to apologise for any inconvenience caused. We have noticed an image arraignment error in our published article (https://doi.org/10.1016/j.jare.2022.06.012) which we would like to correct. The error is related to Fig 4a where in Day 3 of treatment, images of EPS (1 mg/mL) and EPS (5 mg/mL) are the same. in fact, it should be a different image for EPS (5 mg/mL). This was caused by an error that occurred while arranging the images in the PowerPoint slides when compiling the images by our collaborator responsible for animal studies. the correct image of EPS (5 mg/mL) for day 3 is shared in this file. This error had no effect on the provided discussion and outcome of the study. The correct figure 4a is as below:[Figure presented]

2024

Bioactive ECM-mimicking nerve guidance conduit for enhancing peripheral nerve repair

Extensive research efforts are being directed towards identifying alternatives to autografts for the treatment of peripheral nerve injuries (PNIs) with engineered nerve conduits (NGCs) identified as having potential for PNI patients. These NGCs, however, may not fulfill the necessary criteria for a successful transplant, such as sufficient mechanical structural support and functionalization. To address the aforementioned limitations of NGCs, the present investigation explored the development of double cross-linked hydrogels (o-CSMA-E) that integrate the biocompatibility of porcine tendon extracellular matrix (ECM) with the antimicrobial and conductive properties of methacrylated quaternary chitosan. The hydrogels had matrices that could promote the growth of axons and the transmission of neural signals. The hydrogels were subsequently incorporated into a nanofibrous PLLA-ZnO sheath scaffold (ZnO@PLLA) to emulate the natural nerve structure, guiding cell growth and facilitating nerve regeneration. The collaboration of core and sheath materials in ZnO@PLLA/o-CSMA-E nerve guidance conduits resulted in enhanced migration of Schwann cells, formation of myelin sheaths, and improved locomotion performance in rats with sciatic nerve defects when in vivo studies were undertaken. Notably, the in vivo studies demonstrated the similarity between the newly developed engineered NGCs and autologous transplants, with the newly engineered NGCs possessing the potential to promote functional recovery by mimicking the tubular structure and ECM of nerves.

Fabrication of injectable, adhesive, self-healing, superabsorbent hydrogels based on quaternary ammonium chitosan and oxidized pullulan

Injectable hydrogels, which are polymeric materials that are characterized by their ability to be injected in a liquid form into cavities and subsequently undergo in situ solidification, have garnered significant attention. These materials are extensively used in a range of biomedical applications. This study synthesized several injectable composite hydrogels through the mild Schiff base reaction while imposing different concentrations of quaternary ammonium chitosan and oxidized pullulan. Subsequent characterizations revealed a consistent and coherent porous structure within the hydrogels with smooth inner walls. The hydrogels were also determined to possess good adhesion, mechanical properties, self-healing ability, and injectability. Furthermore, antimicrobial tests against Escherichia coli and Staphylococcus aureus demonstrated antibacterial properties, which improved with increasing concentrations of quaternary ammonium chitosan. Co-culturing with skin fibroblasts demonstrated that the injectable hydrogels exhibited favourable biocompatibility and the capacity to boost cellular activity, thus underscoring its potential for use in biomedical applications.

Fabrication and Properties of Hydrogel Dressings Based on Genipin Crosslinked Chondroitin Sulfate and Chitosan

Multifunctional hydrogel dressings remain highly sought after for the promotion of skin wound regeneration. In the present study, multifunctional CHS-DA/HACC (CH) hydrogels with an interpenetrated network were constructed using hydroxypropyl trimethyl ammonium chloride modified chitosan (HACC) and dopamine-modified chondroitin sulfate (CHS-DA), using genipin as crosslinker. The synthesis of HACC and CHS-DA was effectively confirmed using Fourier transform infrared (FT-IR) analysis and 1H nuclear magnetic resonance (1H NMR) spectroscopy. The prepared CH hydrogels exhibited a network of interconnected pores within the microstructure. Furthermore, rheological testing demonstrated that CH hydrogels exhibited strong mechanical properties, stability, and injectability. Further characterization investigations showed that the CH hydrogels showed favorable self-healing and self-adhesion properties. It was also shown that increasing HACC concentration ratio was positively correlated with the antibacterial activity of CH hydrogels, as evidenced by their resistance to Escherichia coli and Staphylococcus aureus. Additionally, Cell Counting Kit-8 (CCK-8) tests, fluorescent images, and a cell scratch assay demonstrated that CH hydrogels had good biocompatibility and cell migration ability. The multifunctional interpenetrated network hydrogels were shown to have good antibacterial properties, antioxidant properties, stable storage modulus and loss modulus, injectable properties, self-healing properties, and biocompatibility, highlighting their potential as wound dressings in wound healing applications.

Eco-Friendly Carbon Nanotubes Reinforced with Sodium Alginate/Polyacrylic Acid for Enhanced Adsorption of Copper Ions: Kinetics, Isotherm, and Mechanism Adsorption Studies

This study investigates the removal efficiency of Cu2+ from wastewater using a composite hydrogel made of carbon nanotubes (CNTs), sodium alginate (SA), and polyacrylic acid (PAA) prepared by free radical polymerization. The CNTs@SA/PAA hydrogel's structure and properties were characterized using SEM, TEM, FTIR, XRD, rheology, DSC, EDS, elemental mapping analysis, and swelling. The adsorption performance for Cu2+ was tested in batch adsorption experiments, considering the pH, dosage, initial concentration, and contact time. The optimal conditions for Cu2+ removal were pH 5.0, an adsorbent dosage of 500 mg/L, and a contact time of 360 min. The adsorption followed pseudo-second order kinetics. Isotherm analyses (Langmuir, Freundlich, Temkin, Dubinin-Radushkevich, Sips, Toth, and Khan) revealed that the Freundlich isotherm best described the adsorption, with a maximum capacity of 358.52 mg/g. A thermodynamic analysis indicated that physical adsorption was the main interaction, with the spontaneity of the process also demonstrated. This study highlights the high efficiency and environmental friendliness of CNT@SA/PAA composites for Cu2+ removal from wastewater, offering a promising approach for water treatment.

Hyaluronic Acid Role in Biomaterials Prevascularization

Tissue vascularization is a major challenge and a bottleneck in tissue engineering. In this review, we explore state of the art on the intricate role of hyaluronic acid (HA) in angiogenesis. HA plays a twofold role in angiogenesis. Firstly, when released as a free polymer in the extracellular matrix (ECM), HA acts as a signaling molecule triggering multiple cascades that foster smooth muscle cells differentiation, migration, and proliferation thereby contributing to vessel wall thickening. Simultaneously, HA bound to the plasma membrane in the pericellular space functions as a polymer block, participating in vessel formation. Starting with the HA origins in native vascular tissues, we review the approaches aimed at achieving vascularization in vivo. The significance of HA molecular weight (MW) in angiogenesis is reviewed and we conscientiously address the challenges associated with utilizing HA in vascular tissue engineering (VTE). The review finally focuses on a thorough examination and comparison of the diverse strategies adopted to harness the benefits of HA in the vascularization of bioengineered materials. By providing a nuanced perspective on the multifaceted role of HA in angiogenesis, this review contributes to the ongoing discourse in tissue engineering and advances our collective understanding of optimizing vascularization processes assisted by functional biomaterials.

A comprehensive review of recent advances in the applications and biosynthesis of oxalic acid from bio-derived substrates

Organic acids are important compounds with numerous applications in different industries. This work presents a comprehensive review of the biological synthesis of oxalic acid, an important organic acid with many industrial applications. Due to its important applications in pharmaceuticals, textiles, metal recovery, and chemical and metallurgical industries, the global demand for oxalic acid has increased. As a result, there is an increasing need to develop more environmentally friendly and economically attractive alternatives to chemical synthesis methods, which has led to an increased focus on microbial fermentation processes. This review discusses the specific strategies for microbial production of oxalic acid, focusing on the benefits of using bio-derived substrates to improve the economics of the process and promote a circular economy in comparison with chemical synthesis. This review provides a comprehensive analysis of the various fermentation methods, fermenting microorganisms, and the biochemistry of oxalic acid production. It also highlights key sustainability challenges and considerations related to oxalic acid biosynthesis, providing important direction for further research. By providing and critically analyzing the most recent information in the literature, this review serves as a comprehensive resource for understanding the biosynthesis of oxalic acid, addressing critical research gaps, and future advances in the field.

Constructing Nerve Guidance Conduit using dECM-Doped Conductive Hydrogel to Promote Peripheral Nerve Regeneration

Peripheral nerve injury often leads to the loss of neurological functions due to the slow regeneration rate and inefficient functional reconstruction. Current clinical treatments using nerve guidance conduits (NGCs) still face challenges in providing a biomimetic microenvironment to promote nerve repair. Herein, decellularized extracellular matrix (dECM) is obtained from porcine Achilles tendon and crosslinked with 3-amino-4-methoxybenzoic acid grafted gelatin (PAMB-G) to obtain conductive hydrogels. Then, a novel nerve guidance conduit is developed by assembling poly(vinyl alcohol) (PVA) conduit and conductive ECM@PAMB-G hydrogel. This bioengineered ECM@PAMB-G/PVA conduit demonstrated excellent cytocompatibility, electrical conductivity, mechanical properties, and biodegradability. In vitro experiments confirmed that the ECM@PAMB-G hydrogel significantly promotes the proliferation and migration of PC12 cells and primary Schwann cells, as well as the growth of dorsal root ganglion (DRG) axons. Furthermore, in vivo studies in a rat sciatic nerve model exhibited improvements in axonal regeneration, Schwann cell migration, myelin sheath formation, and functional recovery mediated by the ECM@PAMB-G/PVA conduit. This work demonstrates the synergistic effects of extracellular matrix and electrical cues in enhancing peripheral nerve regeneration. The ECM@PAMB-G/PVA nerve guidance conduit shows potential as an alternative to autografts for supporting peripheral nerve reconstruction.

Fabrication and characteristics of multifunctional hydrogel dressings using dopamine modified hyaluronic acid and phenylboronic acid modified chitosan

The healing of damaged skin is a complex and dynamic process, and the multi-functional hydrogel dressings could promote skin tissue healing. This study, therefore, explored the development of a composite multifunctional hydrogel (HDCP) by incorporating the dopamine modified hyaluronic acid (HA-DA) and phenylboronic acid modified chitosan (CS-PBA) crosslinked using boric acid ester bonds. The integration of HA-DA and CS-PBA could be confirmed using the Fourier transform infrared spectrometer and 1 H nuclear magnetic resonance analyses. The fabricated HDCP hydrogels exhibited porous structure, elastic solid behavior, shear-thinning, and adhesion properties. Furthermore, the HDCP hydrogels exhibited antibacterial efficacy against Gram-negative Escherichia coli ( E. coli ) and Gram-positive Staphylococcus aureus ( S. aureus ). Subsequently, the cytocompatibility of the HDCP hydrogels was verified through CCK-8 assay and fluorescent image analysis following co-cultivation with NIH-3T3 cells. This research presents an innovative multifunctional hydrogel that holds promise as a wound dressing for various applications within the realm of wound healing.

Phloridzin functionalized gelatin-based scaffold for bone tissue engineering

Polyphenol-functionalized biomaterials are significant in the field of bone tissue engineering (BTE) due to their antioxidant, anti-inflammatory, and osteoinductive properties. In this study, a gelatin (Gel)-based scaffold was functionalized with phloridzin (Ph), the primary polyphenol in apple by-products, to investigate its influence on physicochemical and morphological, properties of the scaffold for BTE application. A preliminary assessment of the biological properties of the functionalized scaffold was also undertaken. The Ph-functionalized scaffold (Gel/Ph) exhibited a porous structure with high porosity (71.3 ± 0.3 %), a pore size of 206.5 ± 1.7 μm, and a radical scavenging activity exceeding 70 %. This scaffold with Young's modulus of 10.8 MPa was determined to support cell proliferation and exhibited cytocompatibility with mesenchymal stem cells (MSCs). Incorporating hydroxyapatite nanoparticle (HA) in the Gel/Ph scaffold stimulated the osteogenic differentiation of key osteogenic genes, including Runx2, ALPL, COL1A1, and OSX ultimately promoting mineralization. This research highlights the promising potential of utilizing polyphenolic compounds derived from fruit waste to functionalize scaffolds for BTE applications.

Comparative analysis of bioenergy and mycoprotein production from apple pomace: Strategies for enhancement and environmental benefits

Apple pomace constitutes a major waste stream of the food processing industry that is characterized by high concentrations of free sugars and structural carbohydrates. This study comparatively explored alternative apple pomace valorization strategies. To this regard, the integration of hydrothermal and organic acid pretreatment as a strategy to enhance anaerobic digestion biomethane yield and alternative production of mycoprotein as a valuable secondary product via the use of Aspergillus oryzae and Neurospora intermedia edible fungi were investigated. In scenario 1, both pretreatment liquors and solid residues underwent anaerobic digestion to produce biomethane. In scenario 2, pretreatment liquors and solid residues underwent fungal cultivation and anaerobic digestion, respectively. Additionally, to optimize bioenergy yield and minimize wastewater generation in scenario 2, the fungal growth effluent was also subjected to anaerobic digestion. In scenario 1, employing methane for transportation showed the potential to decrease GHG by 314.8 kt CO2 eq, translating to US$72.4 million in social cost savings. Similarly, in scenario 2, replacing edible fungal biomass in the food market could lead to a substantial reduction in emissions by 824.2 kt CO2 eq and a corresponding US$227.0 million in social cost savings.

Genipin crosslinked quaternary ammonium chitosan hydrogels for wound dressings

Abstract Bacterial infection can lead to various complications, such as inflammations on surrounding tissues, which can prolong wound healing and thus represent a significant clinical and public healthcare problem. Herein, a report on the fabrication of a novel genipin/quaternized chitosan (CS) hydrogel for wound dressing is presented. The hydrogel was prepared by mixing quaternized CS and genipin under 35 °C bath. The hydrogels showed porous structure (250-500 μm) and mechanical properties (3000-6000 Pa). In addition, the hydrogels displayed self-healing ability and adhesion performance on different substrates. Genipin crosslinked quaternized CS hydrogels showed antibacterial activities against E. coli and S. aureus . The CCK-8 and fluorescent images confirmed the cytocompatibility of hydrogels by seeding with NIH-3T3 cells. The present study showed that the prepared hydrogel has the potential to be used as wound dressing.

Accelerated, injectable, self-healing, scarless wound dressings using rGO reinforced dextran/chitosan hydrogels incorporated with PDA-loaded asiaticoside

The process of wound healing is intricate and complex, necessitating the intricate coordination of various cell types and bioactive molecules. Despite significant advances, challenges persist in achieving accelerated healing and minimizing scar formation. Herein, a multifunctional hydrogel engineered via dynamic Schiff base crosslinking between oxidized dextran and quaternized chitosan, reinforced with reduced graphene oxide (rGO) is reported. The resulting OQG hydrogels demonstrated injectability to aid in conforming to irregular wound geometries, rapid self-healing to maintain structural integrity and adhesion for intimate integration with wound beds. Moreover, the developed hydrogels possessed antioxidant and antibacterial activities, mitigating inflammation and preventing infection. The incorporation of conductive rGO further facilitated the transmission of endogenous electrical signals, stimulating cell migration and tissue regeneration. In addition, the polydopamine-encapsulated asiaticoside (AC@PDA) nanoparticles were encapsulated in OQG hydrogels to reduce scar formation during in vivo evaluations. In vitro results confirmed the histocompatibility of the hydrogels to promote cell migration. The recovery of the full-thickness rat wounds revealed that these designed OQG hydrogels with the incorporation of AC@PDA nanoparticles could accelerate wound healing, reduce inflammation, facilitate angiogenesis, and minimize scarring when implemented. This multifunctional hydrogel system offers a promising strategy for enhanced wound management and scarless tissue regeneration, addressing the multifaceted challenges in wound care.

The technical, economic, and environmental assessment of solvothermal liquefaction processes: An experimental and simulation study on the influence of solvent reichardt parameter

This study explored solvothermal liquefaction (STL) as a viable method for repurposing food waste (FW). Various solvents with different Reichardt parameters were used to facilitate liquefaction, and their impacts on biocrude yields were analyzed. Notably, among the solvents investigated, water and ethanol yielded the highest biocrude yields of 24.7 wt% and 23.6 wt%, respectively. Synergistic effects from combining these solvents were also observed, resulting in enhanced biocrude yields. The STL process was simulated using ASPEN Plus to evaluate its economic feasibility, including sensitivity analysis on input data. Additionally, a negative non-linear correlation was found between net greenhouse emissions and processing capacity. The study determined that the environmental performance of STL becomes less competitive compared to FW landfilling when process capacity falls below a minimum level. Overall, these findings highlight the potential of STL technology for FW management, offering both economic and environmental benefits.

Biomaterial ink based on bacterial polyglucuronic acid for tissue engineering applications

This study focuses on the development of printable biomaterial inks using a bacterial exopolysaccharide (EPS) called polyglucuronic acid (PGU), along with bacterial cellulose (BC) or methylcellulose (MC). The physical, mechanical, and biological properties of the hydrogels originating from these inks were assessed through scanning electron microscope (SEM) imaging, rheological tests, and cytocompatibility assessments. The results demonstrate that incorporating PGU into BC or MC inks enhances the shape fidelity, printability, and rigidity of the resulting 3D-printed hydrogels. Moreover, all crosslinked hydrogels based on PGU and BC or MC exhibited cytocompatibility with fibroblast cells (3T3-L1). These findings highlight the potential of the PGU/BC or MC-based biomaterial inks for various tissue engineering applications, including injectable gels, drug delivery systems, and soft tissue models. Furthermore, the study underscores the potential of using bacterial PGU as an alternative to alginate in biomaterial ink development and 3D printing.

Designing and synthesis of injectable hydrogel based on carboxymethyl cellulose/carboxymethyl chitosan containing QK peptide for femoral head osteonecrosis healing

Femoral head necrosis is a debilitating disorder that typically caused by impaired blood supply to the hip joint. In this study, a novel injectable hydrogel based on Oxidized Carboxymethyl Cellulose (OCMC)-Carboxymethyl Chitosan (CMCS) polymers containing an angiogenesis stimulator peptide (QK) with a non-toxic crosslinking interaction (Schiff based reaction) was synthesized to enhance angiogenesis following femoral head necrosis in an animal model. The physicochemical features of fabricated injectable hydrogel were analyzed by FTIR, swelling and degradation rate, rheometry, and peptide release. Also, the safety and efficacy were evaluated following an in vitro hydrogel injection study and an avascular necrosis (AVN) animal model. According to the results, the hydrogel exhibited an appropriate swelling ratio and water uptake (>90 %, 24 h) as well as a suitable degradation rate over 21 days accompanied by a continuous peptide release. Also, data showed that hydrogels containing QK peptide boosted the proliferation, differentiation, angiogenesis, and osteogenic potential of both Bone Marrow mesenchymal Stem Cells (BM-MSCs) and human umbilical vein endothelial cells (HUVECs) (****p < 0.0001 and ***p < 0.001, respectively). Furthermore, molecular and histological evaluations significantly demonstrated the overexpression of Runx2, Osteocalcin, Collagen I, VEGF and CD34 genes (**p < 0.01 and ***p < 0.001, respectively), and also femoral head necrosis was effectively prohibited, and more blood vessels were detected in defect area by OCMC-CMCS hydrogel containing QK peptide (bone trabeculae >9000, ***p < 0.001). In conclusion, the findings demonstrate that OCMC-CMCS-QK injectable hydrogel could be considered as an impressive therapeutic construct for femoral head AVN healing.

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990-2021

Background: Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. Methods: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model—a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates—with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality—which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. Findings: The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. Interpretation: Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. Funding: Bill & Melinda Gates Foundation.

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950-2021, and the impact of the COVID-19 pandemic

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020-21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5-65·1] decline), and increased during the COVID-19 pandemic period (2020-21; 5·1% [0·9-9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98-5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50-6·01) in 2019. An estimated 131 million (126-137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7-17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8-24·8), from 49·0 years (46·7-51·3) to 71·7 years (70·9-72·5). Global life expectancy at birth declined by 1·6 years (1·0-2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67-8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4-52·7]) and south Asia (26·3% [9·0-44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic. Funding: Bill & Melinda Gates Foundation.

Recent Advances of Chitosan-Based Hydrogels for Skin-Wound Dressings

The management of wound healing represents a significant clinical challenge due to the complicated processes involved. Chitosan has remarkable properties that effectively prevent certain microorganisms from entering the body and positively influence both red blood cell aggregation and platelet adhesion and aggregation in the bloodstream, resulting in a favorable hemostatic outcome. In recent years, chitosan-based hydrogels have been widely used as wound dressings due to their biodegradability, biocompatibility, safety, non-toxicity, bioadhesiveness, and soft texture resembling the extracellular matrix. This article first summarizes an overview of the main chemical modifications of chitosan for wound dressings and then reviews the desired properties of chitosan-based hydrogel dressings. The applications of chitosan-based hydrogels in wound healing, including burn wounds, surgical wounds, infected wounds, and diabetic wounds are then discussed. Finally, future prospects for chitosan-based hydrogels as wound dressings are discussed. It is anticipated that this review will form a basis for the development of a range of chitosan-based hydrogel dressings for clinical treatment.

Rizatriptan benzoate-loaded dissolving microneedle patch for management of acute migraine therapy

In this study, dissolving microneedles (MNs) using polyvinyl alcohol (PVA) and poly (1-vinylpyrrolidone-co-vinyl acetate) (P(VP-co-VA)) as matrix materials were developed for transdermal delivery of rizatriptan benzoate (RB) for acute migraine treatment. In-vitro permeation studies were conducted to assess the feasibility of the as-fabricated dissolving MNs to release RB. Drug skin penetration were tested by Franz diffusion cells, showing an increase of the transdermal flux compared to passive diffusion due to the as-fabricated dissolving MNs having a sufficient mechanical strength to penetrate the skin and form microchannels. The pharmacological study in vivo showed that RB-loaded dissolving MNs significantly alleviated migraine-related response by up-regulating the level of 5-hydroxytryptamine (5-HT) and down-regulating the levels of calcitonin gene-related peptide (CGRP) and substance P (SP). In conclusion, the RB-loaded dissolving MNs have advantages of safety, convenience, and high efficacy over conventional administrations, laying a foundation for the transdermal drug delivery system treatment for acute migraine.

Management of secondary effluent using novel membrane technology to recover water and magnesium ions for phosphate precipitation: An integrated pilot-scale study

Phosphorus and magnesium are comprised as essential resources in the European Union's list of critical raw materials. Access to those nutrients together with growing potable water demand is becoming a serious problem. Many efforts have been made to develop effective technologies for recycling water and essential nutrients from wastewater over the past few decades. Here, we present a new approach for the recovery of water simultaneously with the reclamation of Mg2+ and phosphates from secondary effluent (SE) and anaerobic digestion liquor (ADL) at WWTPs. Following the circular economy principles, our technology manages SE and produces two important products, (1) pure water (permeates) and (2) Mg-rich concentrates (by-streams/retentates), for further phosphate recovery from ADL in the form of struvite (MAP). The present study proposes an approach of combining energy-saving membrane processes (ultrafiltration (UF) and nanofiltration (NF)) with ionic exchange (IE) with the UF-NF-IE-NF-concentrates serving as a source of Mg2+ in struvite (MAP) precipitation from ADL. Different reaction conditions led to the development of typical MAP crystal forms, such as pyramids, needles, and x-shapes. The study also demonstrated that due to the low heavy metal content and narrow size distribution, the MAP generated could also be employed as a fertilizer.

Red blood cell membrane-coated functionalized Cu-doped metal organic framework nanoformulations as a biomimetic platform for improved chemo-/chemodynamic/photothermal synergistic therapy

Nanoformulations for combining chemotherapy, chemodynamic therapy, and photothermal therapy have enormous potential in tumor treatment. Coating nanoformulations with cell membranes endows them with homologous cellular mimicry, enabling nanoformulations to acquire new functions and properties, including homologous targeting and long circulation in vivo, and can enhance internalization by homologous cancer cells. Herein, we fused multifunctional biomimetic nanoformulations based on Cu-doped zeolitic imidazolate framework-8 (ZIF-8). Hydroxycamptothecin (HCPT), a clinical anti-tumor drug, was encapsulated into ZIF-8, which was subsequently coated with polydopamine (PDA) and red blood cell membrane. The as-fabricated biomimetic nanoformulations showed an enhanced cell uptake in vitro and the potential to prolong blood circulation in vivo, producing effective synergistic chemotherapy, chemodynamic therapy, and photothermal therapy under the 808 nm laser irradiation. Together, the biomimetic nanoformulations showed a prolonged blood circulation and evasion of immune recognition in vivo to provide a bio-inspired strategy which may have the potential for the multi-synergistic therapy of breast cancer.

Fabrication of lidocaine-loaded polymer dissolving microneedles for rapid and prolonged local anesthesia

There is an urgent need for research into effective interventions for pain management to improve patients' life quality. Traditional needle and syringe injection were used to administer the local anesthesia. However, it causes various discomforts, ranging from brief stings to trypanophobia and denial of medical operations. In this study, a dissolving microneedles (MNs) system made of composite matrix materials of polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), and sodium hyaluronate (HA) was successfully developed for the loading of lidocaine hydrochloride (LidH). The morphology, size and mechanical properties of the MNs were also investigated. After the insertion of MNs into the skin, the matrix at the tip of the MNs was swelled and dissolved by absorption of interstitial fluid, leading to a rapid release of loaded LidH from MNs' tips. And the LidH in the back patching was diffused into deeper skin tissue through microchannels created by MNs insertion, forming a prolonged anesthesia effect. In addition, the back patching of MNs could be acted as a drug reservoir to form a prolonged local anesthesia effect. The results showed that LidH MNs provided a superior analgesia up to 8 h, exhibiting a rapid and long-lasting analgesic effects. Additionally, tissue sectioning and in vitro cytotoxicity tests indicated that the MNs patch we developed had a favorable biosafety profile.

Hollow-adjustable polymer microneedles for prolonged hypoglycemic effect on diabetic rats

Maintaining blood glucose levels within a safe range is critical for diabetic management. In recent decades, microneedles (MNs) have emerged as a potential method for delivering drugs to treat diabetes. However, insufficient drug loading and the complexity of achieving long-acting release have presented challenges that research has not addressed well. In this study, the hollow-adjustable biocompatible polymer MNs with varying cavity volumes were developed by cyclic freeze-thawing technique. The structure of shell-layer of hollow MNs was optimized with a sequential casting approach for regulating drug release kinetics. This design can ensure the sufficient mechanical strength of MNs and help to improve the drug-loading capacity, thereby solving the problem of low drug-loading capacity and short pharmacodynamic action time of traditional polymer MNs. In vivo experiments performed on diabetic rat models revealed the potential of the as-fabricated MNs to effectively pierce into the skin, leading to a notable hypoglycemic effect lasting up to 14 h without inducing the risk of hypoglycemia. These results indicate that the fabricated hollow-adjustable polymer MNs is a potential candidate for transdermal delivery of high-dose drugs.

Starch biocomposites preparation by incorporating organosolv lignins from potato crop residues

Plastic wastes accumulated due to food packaging pose environmental threats. This study proposes biopolymeric films containing lignins extracted from potato crop residues (PCR) through organosolv treatment as a green alternative to non-degradable food packaging. The isolation process yielded 43.9 wt% lignins with a recovery rate of 73.5 wt% achieved under optimum conditions at 180 °C with 50 % v/v ethanol. The extracted lignins were then incorporated into a starch matrix to create biocomposite films. ATR-FTIR analysis confirmed interactions between the starch matrix and extracted lignins, and XRD analysis showed the amorphous structure of lignins, reducing film crystallinity. The addition of 1 wt% of extracted lignins resulted in a 87 % reduction in oxygen permeability, a 25 % increase in the thermal stability of the film, and a 78 % enhancement in antioxidant. Furthermore, introducing 3 wt% lignins led to the lowest water vapor transmission rate, measuring 9.3 × 10−7 kg/s·m2. Morphological studies of the films demonstrated a homogeneous and continuous structure on both the surface and cross-sectional areas when the lignins content was below 7 wt%. These findings highlight the potential of using organosolv lignins derived from potato crop residues as a promising additive for developing eco-friendly films designed for sustainable food packaging.

Facile preparation of self-healing hydrogels based on chitosan and PVA with the incorporation of curcumin-loaded micelles for wound dressings

Abstract The increased demand for improved strategies for wound healing has, in recent years, motivated the development of multifunctional hydrogels with favorable bio-compatibility and antibacterial properties. To this regard, the current study presented the design of a novel self-healing composite hydrogel that could perform as wound dressing for the promotion of wound healing. The composite hydrogels were composed of polyvinyl alcohol (PVA), borax and chitosan functionalized with sialic acid (SA-CS) and curcumin loaded pluronic F127 micelles. The hydrogels were formed through the boronic ester bond formation between PVA, SA-CS and borax under physiological conditions and demonstrated adjustable mechanical properties, gelation kinetics and antibacterial properties. When incubating with NIH3T3 cells, the hydrogels also demonstrated good biocompatibility. These aspects offer a promising foundation for their prospective applications in developing clinical materials for wound healing.

Gas Therapy: Generating, Delivery, and Biomedical Applications

Abstract Oxygen (O 2 ), nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H 2 S), and hydrogen (H 2 ) with direct effects, and carbon dioxide (CO 2 ) with complementary effects on the condition of various diseases are known as therapeutic gases. The targeted delivery and in situ generation of these therapeutic gases with controllable release at the site of disease has attracted attention to avoid the risk of gas poisoning and improve their performance in treating various diseases such as cancer therapy, cardiovascular therapy, bone tissue engineering, and wound healing. Stimuli‐responsive gas‐generating sources and delivery systems based on biomaterials that enable on‐demand and controllable release are promising approaches for precise gas therapy. This work highlights current advances in the design and development of new approaches and systems to generate and deliver therapeutic gases at the site of disease with on‐demand release behavior. The performance of the delivered gases in various biomedical applications is then discussed.

Core-shell structured microneedles with programmed drug release functions for prolonged hyperuricemia management

An appropriate non-oral platform via transdermal delivery of drugs is highly recommended for the treatment of hyperuricemia. Herein, a core-shell structured microneedle array patch with programmed drug release functions was designed to regulate serum...

Advanced PEG-tyramine biomaterial ink for precision engineering of perfusable and flexible small-diameter vascular constructs via coaxial printing

Vascularization is crucial for providing nutrients and oxygen to cells while removing waste. Despite advances in 3D-bioprinting, the fabrication of structures with void spaces and channels remains challenging. This study presents a novel approach to create robust yet flexible and permeable small (600-1300 μm) artificial vessels in a single processing step using 3D coaxial extrusion printing of a biomaterial ink, based on tyramine-modified polyethylene glycol (PEG-Tyr). We combined the gelatin biocompatibility/activity, robustness of PEG-Tyr and alginate with the shear-thinning properties of methylcellulose (MC) in a new biomaterial ink for the fabrication of bioinspired vessels. Chemical characterization using NMR and FTIR spectroscopy confirmed the successful modification of PEG with Tyr and rheological characterization indicated that the addition of PEG-Tyr decreased the viscosity of the ink. Enzyme-mediated crosslinking of PEG-Tyr allowed the formation of covalent crosslinks within the hydrogel chains, ensuring its stability. PEG-Tyr units improved the mechanical properties of the material, resulting in stretchable and elastic constructs without compromising cell viability and adhesion. The printed vessel structures displayed uniform wall thickness, shape retention, improved elasticity, permeability, and colonization by endothelial-derived - EA.hy926 cells. The chorioallantoic membrane (CAM) and in vivo assays demonstrated the hydrogel's ability to support neoangiogenesis. The hydrogel material with PEG-Tyr modification holds promise for vascular tissue engineering applications, providing a flexible, biocompatible, and functional platform for the fabrication of vascular structures.

Magnetic Force Microscopy and Nanoindentation on 3D Printed Magnetic Scaffolds for Neuronal Cell Growth

This study investigated the physicochemical properties of 3D printed sodium alginate (SA)/poly(vinyl alcohol) (PVA)-magnetic nanoparticle (MNP) hydrogels that were subsequently cross-linked using Ca2+ ions via postspraying. The rheological properties of the precursor hydrogels were assessed because they play a crucial role in printability. The SA/PVA composition of 12/8 wt %, both in the absence and presence of MNPs at concentrations of 1.0 mg/mL, 2.5 mg/mL, or 5.0 mg/mL, displayed good printability. Magnetic force microscopy (MFM) evidenced the random distribution of MNPs on the hydrogel surface and the aggregation of magnetic clusters with increasing MNP content. Nanoindentation tests using a silica colloidal probe allowed estimating the elastic modulus values of swollen 3D printed scaffolds. These values ranged from 1.0 MPa (SA12/PVA8) to 7.2 MPa (SA/PVA-MNP5). Confocal microscopy confirmed the presence of cells within the interior of the 3D printed scaffolds. The cytocompatibility or cytotoxicity assays showed that all 3D printed scaffolds were cytocompatible with HT-22 cells.

Self-adhesive and self-healing hydrogel dressings based on quaternary ammonium chitosan and host-guest interacted silk fibroin

Skin is susceptible to varying degrees of injury from external forces, heat, disease, and chemical corrosion. Wound dressings using tissue engineering principles can accelerate skin tissue repair, relieve patient pain, and reduce the formation of scars. In this study, the self-adhesive and self-healing hydrogel dressings based on quaternary ammonium chitosan (QCS), β-cyclodextrin-modified silk fibroin (CD-SF), and adamantane-modified silk fibroin (AD-SF), that was designed. The formed hydrogels not only based on the host-guest interactions between CD-SF as host polymer and AD-SF as guest polymer, also the hydrogen-bonding assembly from QCS was combined. The successful synthesis of QCS, CD-SF, and AD-SF was established using Fourier Transform Infrared spectroscopy (FT-IR) and 1H nuclear magnetic resonance (1H NMR) spectroscopy. The obtained QCS/CD-SF/AD-SF (QCA) hydrogels displayed self-adhesive, self-healing, and mechanical properties. The hydrogels exhibited antibacterial performance, combating typical Gram-negative bacteria Escherichia coli (E. coli) and Gram-positive bacteria Staphylococcus aureus (S. aureus). Further, CCK-8 assay by incubating hydrogels with NIH-3T3 cells and optical microscope inspection of cell morphology indicates the excellent cytocompatibility of the hydrogels. The designed QCA hydrogel with antibacterial properties and biocompatibility have great potential as wound dressings for wound healing treatment.

Sustainable biorefinery development for valorizing all wastes from date palm agroindustry

This study examined how various residues from date palm agroindustrial can be utilized in a biorefinery platform to produce ethanol, methane, and lignin. Liquid hot water, ethanol organosolv, and catalyzed ethanol organosolv (CEO) pretreatments were applied to trunk, leaves, leaf sheath, pedicels, date cake, and seeds. The process included extracting lignin from the liquid fraction, followed by converting the pretreated solid material into ethanol. The fermentation residues were also utilized to produce biomethane through anaerobic digestion. Two different scenarios were employed for the biorefining, i.e., (Ⅰ) maximum lignin production and (Ⅱ) maximum biofuel production. The best results for the first scenario were obtained when CEO was employed in the pretreatment of date palm wastes, where 806.9 mL ethanol, 902.8 L methane, and 528.0 g lignin were produced from each kg of each residue. In energetic terms, the biofuel products (i.e., ethanol and methane) were determined to have a combined energy content equivalent to 1553.1 mL of gasoline. Likewise, the most favorable outcomes of the second scenario were obtained by incorporating CEO pretreatment of trunk, leaf sheath, leaves, and pedicels in the valorization of untreated date cake and seeds. Furthermore, for the second scenario, the resulting products were 967.5 mL ethanol, 1605.3 L methane, and 341.0 g lignin, with the biofuel products having a combined energetic content equivalent to 2452.0 mL of gasoline. These findings indicate that the biorefining of date palm agroindustrial wastes has significant potential for bioenergy production.

Graphene-Based Engineered Living Materials

With the rise of engineered living materials (ELMs) as innovative, sustainable and smart systems for diverse engineering and biological applications, global interest in advancing ELMs is on the rise. Graphene-based nanostructures can serve as effective tools to fabricate ELMs. By using graphene-based materials as building units and microorganisms as the designers of the end materials, next-generation ELMs can be engineered with the structural properties of graphene-based materials and the inherent properties of the microorganisms. However, some challenges need to be addressed to fully take advantage of graphene-based nanostructures for the design of next-generation ELMs. This work covers the latest advances in the fabrication and application of graphene-based ELMs. Fabrication strategies of graphene-based ELMs are first categorized, followed by a systematic investigation of the advantages and disadvantages within each category. Next, the potential applications of graphene-based ELMs are covered. Moreover, the challenges associated with fabrication of next-generation graphene-based ELMs are identified and discussed. Based on a comprehensive overview of the literature, the primary challenge limiting the integration of graphene-based nanostructures in ELMs is nanotoxicity arising from synthetic and structural parameters. Finally, we present possible design principles to potentially address these challenges.

2023

Fabrication and In Vitro Characterization of Polycaprolactone/Graphene Oxide/Collagen Nanofibers for Myocardial Repair

Abstract This study is focused on fabricating tissue‐engineered electrospun nanofibers that contain polycaprolactone (PCL), graphene oxide (GO), and collagen (COL) to get an alternative treatment for cardiac injuries. GO (1.5 wt%) is used to support the contraction‐elongation of cardiomyocytes by improving electrical stimulation. The COL (1, 3, and 5 wt%) is the main component of the myocardial extracellular matrix have led to their frequent use in cardiac tissue engineering (CTE). The scanning electron microscope (SEM) images show the homogeneous and bead‐free morphologies of the nanofibers. Adding a high amount (3% and 5%) of COL decreases the tensile strength value of 17% PCL/1.5% GO nanofiber. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐Diphenyltetrazolium Bromide (MTT) assay demonstrates that the COL addition increases cell viability compared to that in 17% PCL/1.5% GO nanofibers on the third day. The response of the nanofibers to alternating current (AC) signal is studied between the frequencies 40 and 10 5  Hz. The direct current (DC) conductivity values of the films are determined to be between 1.10 −10 and 6.10 −10 S m −1 at 25 °C. The AC conductivity values show frequency‐dependent behavior. Among the PCL/GO‐based electrospun nanofibers, 17% PCL/1.5% GO/5% COL nanofiber shows greater DC and AC conductivity than 17% PCL/1.5% GO nanofiber.

Red Blood Cell Membrane-Camouflaged Polydopamine and Bioactive Glass Composite Nanoformulation for Combined Chemo/Chemodynamic/Photothermal Therapy

Combinations of different therapeutic strategies, including chemotherapy (CT), chemodynamic therapy (CDT), and photothermal therapy (PTT), are needed to effectively address evolving drug resistance and the adverse effects of traditional cancer treatment. Herein, a camouflage composite nanoformulation (TCBG@PR), an antitumor agent (tubercidin, Tub) loaded into Cu-doped bioactive glasses (CBGs) and subsequently camouflaged by polydopamine (PDA), and red blood cell membranes (RBCm), was successfully constructed for targeted and synergetic antitumor therapies by combining CT of Tub, CDT of doped copper ions, and PTT of PDA. In addition, the TCBG@PRs composite nanoformulation was camouflaged with a red blood cell membrane (RBCm) to improve biocompatibility, longer blood retention times, and excellent cellular uptake properties. It integrated with long circulation and multimodal synergistic treatment (CT, CDT, and PTT) with the benefit of RBCms to avoid immune clearance for efficient targeted delivery to tumor locations, producing an “all-in-one” nanoplatform. In vivo results showed that the TCBG@PRs composite nanoformulation prolonged blood circulation and improved tumor accumulation. The combination of CT, CDT, and PTT therapies enhanced the antitumor therapeutic activity, and light-triggered drug release reduced systematic toxicity and increased synergistic antitumor effects.

Mechanical investigation of solid MNs penetration into skin using finite element analysis

In the past two decades, MNs patches (MNs) as a promising platform have been extensively investigated for transdermal delivery of drug drugs, cells, and active substances and extraction of bio‐fluids. To realize painless, efficacious and safe transdermal delivery, these MNs must penetrate the skin to the appropriate depth without breaking or bending. Therefore, effective prediction of mechanical properties such as skin penetration of microneedles is crucial for the material and structural design of MNs. In this paper, a numerical simulation of the insertion process of the microneedle into various types of skin modeling is reported using the finite element method. The effective stress failure criterion has been coupled with the element deletion technique to predict the complete insertion process. The numerical results show a good agreement with the reported experimental data for the deformation and failure of the skin and the insertion force. This article is protected by copyright. All rights reserved.

Coaxial 4D printing of vein-inspired thermoresponsive channel hydrogel actuators

Although significant progress has been made in coaxial printing of vascularized tissue models, this technique has not yet been used to fabricate stimulus-responsive scaffolds capable of shape change over time. Here, we propose a new method of direct ink printing with a coaxial nozzle, coaxial 4D printing, enabling the manufacturing of thermoresponsive constructs embedded with a network of interconnected channels. In our approach, a poly(N-isopropylacrylamide) (PNIPAAm)-based thermoink is coaxially extruded into either core/sheath microfibers or microtubes. PNIPAAm renders a hydrogel temperature-sensitive and endows it with a shape-morphing property both at the micro- and macroscale. Specifically, the lumen diameter of the microtubes can be controlled by temperature by 30%. The macrostructural soft actuators can undergo programmed and reversible temperature-dependent shape changes due to the structural anisotropy of the hydrogel. The permeability tests demonstrate that the hydrogel can possess enough strength to maintain the hollow channels without breaking. In vitro tests confirm the biocompatibility of our material with EA.hy926 cells, paving the avenue for new perfusable soft robots, active implants, or vascularized tissue models. Finally, we combined microalgae Chlamydomonas reinhardtii with our hydrogels to fabricate materials having functions of both living microorganisms and stimuli-responsive polymers towards creating engineered living materials (ELMs) with a vein-like geometry.

Fabrication of carboxymethyl cellulose/hyaluronic acid/polyvinylpyrrolidone composite pastes incorporation of minoxidil-loaded ferulic acid-derived lignin nanoparticles and valproic acid for treatment of androgenetic alopecia

Androgenetic alopecia (AGA) is a transracial and cross-gender disease worldwide with a higher prevalence among young individuals. Traditional oral or subcutaneous injections are often used to treat AGA, however, they may cause severe side-effects and therefore effective treatments for AGA are currently lacking. In this work, to treat AGA, we developed a composite paste system based on minoxidil (MXD)-loaded nanoparticles and valproic acid (VPA) with the assistance of roller-microneedles (roller-MNs). The matrix of composite paste systems is carboxymethyl cellulose (CMC), hyaluronic acid (HA) and polyvinylpyrrolidone (PVP). The roller-MNs can create microchannels in the skin to enhance drug transdermal efficiency. With the combined effects of the stimulation hair follicle (HF) regrowth by upregulating Wnt/beta-catenin of VPA and the mechanical microchannels induced by roller-MNs, the as-prepared composite paste systems successfully boost perifollicular vascularization, and activate hair follicle stem cells, thereby inducing notably faster hair regeneration at a lower administration frequency on AGA mouse model compared with minoxidil. This approach offers several benefits, including the avoidance of efficacy loss due to the liver's first-pass effect associated with oral drug, reduction in the risk of infection from subcutaneous injection, and significant decrease in the side effects of lower-dose MXD.

Liposomal oxygen-generating hydrogel for enhancing cell survival under hypoxia condition

The inadequate oxygen supply to engineered tissues has been a persistent challenge in tissue engineering and regenerative medicine. To overcome this limitation, we developed a scaffold combined with an oxygen-releasing liposomal system comprising catalase-loaded liposomes (CAT@Lip) and H2O2-loaded liposomes (H2O2@Lip). This oxygenation system has shown high cytocompatibility when they were applied to human stromal cells. Under hypoxic conditions, the cell viability enclosed in the oxygen-releasing liposomal alginate hydrogel (94.62 ± 3.46 %) was significantly higher than that of cells enclosed in hydrogel without liposomes (47.18 ± 9.68 %). There was no significant difference in cell viability and apoptosis rate compared to normoxia conditions after three days, indicating the effectiveness of the oxygen-releasing approach in hypoxic conditions. In conclusion, our study demonstrates that the use of liposomal oxygen-releasing scaffolds can overcome the oxygen diffusion challenge in tissue implant fabrication, providing a simple solution for cellular oxygenation that could be a crucial element in tissue engineering.

Graphene-Based Engineered Living Materials

With the rise of engineered living materials (ELMs) as innovative, sustainable and smart systems for diverse engineering and biological applications, global interest in advancing ELMs is on the rise. Graphene-based nanostructures can serve as effective tools to fabricate ELMs. By using graphene-based materials as building units and microorganisms as the designers of the end materials, next-generation ELMs can be engineered with the structural properties of graphene-based materials and the inherent properties of the microorganisms. However, some challenges need to be addressed to fully take advantage of graphene-based nanostructures for the design of next-generation ELMs. This work covers the latest advances in the fabrication and application of graphene-based ELMs. Fabrication strategies of graphene-based ELMs are first categorized, followed by a systematic investigation of the advantages and disadvantages within each category. Next, the potential applications of graphene-based ELMs are covered. Moreover, the challenges associated with fabrication of next-generation graphene-based ELMs are identified and discussed. Based on a comprehensive overview of the literature, the primary challenge limiting the integration of graphene-based nanostructures in ELMs is nanotoxicity arising from synthetic and structural parameters. Finally, we present possible design principles to potentially address these challenges.

Alleviating hypoxia through self-generating oxygen and hydrogen peroxide fluorinated chitosan: Insights from a kinetic study

Effective methods to alleviate hypoxia are necessary for the proper healing of chronic wounds. However, current oxygen (O2) delivery methods suffer from limitations, such as low O2 capacity and short supply time, burst release, and inadequate O2 preservation potential. This study presents a new approach utilising fluorinated chitosan (PFC-chitosan) infused with self-generating and preserving O2 and hydrogen peroxide (H2O2). We incorporated calcium peroxide (CaO2)-loaded polycaprolactone (PCL) particles into the PFC-chitosan matrix and subsequently evaluated the release kinetics of O2 and H2O2 from these materials. The incorporation of CaO2 into PCL particles and PFC-chitosan effectively mitigate the rapid decomposition rate of CaO2 while the PFC groups enable the dissolution of generated O2 via Van der Waals interactions. The apparent rate constant (kO2) for O2 release from CaO2 under hypoxia decreased from 1.194 µM−1h−1 to 0.141 µM−1h−1 by incorporating into PCL particles and PFC-chitosan, indicating the slower release of O2 from these materials. Regarding release kinetics, H2O2 follows a pseudo-zero-order pattern, while O2 exhibits a pseudo-first-order pattern. The kO2 is affected by temperature, pH, initial O2 concentration in the release media, and an initial amount of CaO2. The particles with PFC-chitosan showed higher cell viability and slower O2 release rates, indicating improved angiogenesis potential. The simultaneous generation of O2 and H2O2 from PFC-chitosan may have the potential to improve chronic wound healing by providing a continuous supplying of O2.

Tissue adhesive hydrogel based on upcycled proteins and plant polyphenols for enhanced wound healing

This study investigates the potential of keratin and silk as natural structural proteins for designing tissue adhesives for wound healing. The study demonstrates the silk-wool-tannic acid (SF-Wool-TA) complex as an in situ tissue adhesive through the utilization of polyphenol chemistry. Keratin is first isolated from coarse sheep wool using a green microwave treatment process. Due to the presence of functional groups such as tyrosine, carboxyl, and thiol groups; silk, and keratin can form multiple interactions with pyrogallol and catechol functional groups of TA to form an in situ adhesive hydrogel. The SF-Wool-TA hydrogel exhibits in situ gelation, recyclability, moldability, elasticity (G'>100 kPa), adhesiveness, self-healing properties, 3D printability, antibacterial activity, antioxidant properties, and biocompatibility. The inclusion of wool keratin also enhances the hydrophilicity of the hydrogel. The hydrogel was tested in vivo and enhanced wound healing in a full-thickness skin incision model. The keratin-polyphenol interaction represents an attractive hybrid material for advanced biomaterials applications, particularly in the field of skin wound healing.

Synthesis, physicochemical characteristics, cytocompatibility, and antibacterial properties of iron-doped biphasic calcium phosphate nanoparticles with incorporation of silver

Abstract The application of biphasic calcium phosphate (BCP) in tissue engineering and regenerative medicine has been widely explored due to its extensively documented multi-functionality. The present study attempts to synthesize a new type of BCP nanoparticles, characterised with favourable cytocompatibility and antibacterial properties via modifications in their structure, functionality and assemblage, using dopants. In this regard, this study initially synthesized iron-doped BCP (FB) nanoparticles with silver subsequently incorporated into FB nanoparticles to create a nanostructured composite (FB Ag ). The FB and FB Ag nanoparticles were then characterized using Fourier transform infrared spectroscopy, x-ray diffraction, ultraviolet-visible spectroscopy, and x-ray photoelectron spectroscopy. The results showed that silver was present in the FB Ag nanoparticles, with a positive correlation observed between increasing AgNO 3 concentrations and increasing shape irregularity and reduced particle size distribution. Additionally, cell culture tests revealed that both FB and FB Ag nanoparticles were compatible with bone marrow-derived mesenchymal stem cells (hBMSCs). The antibacterial activity of the FB Ag nanoparticles was also tested using Gram-negative E. coli and Gram-positive S. aureus , and was found to be effective against both bacteria. The inhibition rates of FB Ag nanoparticles against E. coli and S. aureus were 33.78 ± 1.69-59.03 ± 2.95%, and 68.48 ± 4.11-89.09 ± 5.35%, respectively. These findings suggest that the FB Ag nanoparticles have potential use in future biomedical applications.

Optimizing the subcritical water valorization of insect (Hermetia illucens l.) farming waste for biodiesel production

To counter the proliferation of secondary waste streams generated on insect (black soldier fly) farms, the present study integrated green water technology and acid-catalyzed transesterification as a basis to assess further value extraction potentials. By valorizing the waste streams, a process was developed to promote the circular economy paradigm. In this regard, wastes generated from a local insect farm were initially subjected to subcritical water extraction (SWE) for lipid recovery. The SWE process was optimized such that an enhanced lipid yield of 13.31 wt% was obtained at temperature, time, and solid loading conditions of 236.8 °C, 10 min of extraction, and 1 g/ 100 mL respectively. The lipids recovered were then subjected to an acid-catalyzed transesterification reaction for the production of a fatty acid methyl ester (FAME) mixture. A preliminary economic assessment of the process was also undertaken. The results showed that the wastes had the potential to be economically employed in the production of biodiesel that satisfied fuel property standards. In addition, the potential of employing the side streams as an animal feed was also highlighted due to the determined dominance of oligopeptides, which are known for their favorable bioactive properties. The results indicated that insect farming waste is a promising renewable source for high-quality biodiesel and animal feed production through the environmentally friendly biorefinery.

Click chemistry for 3D bioprinting

Bioinks are employed in the fabrication of 3D scaffolds containing cells and macromolecules that can be applied in regenerative medicine.

Optimizing phenol-modified hyaluronic acid for designing shape-maintaining biofabricated hydrogel scaffolds in soft tissue engineering

In this study, we developed a well-printable biomaterial ink for 3D printing of shape-maintaining hydrogel scaffolds. The hydrogel base comprised tyramine-modified hyaluronic acid (HA-Tyr) and gelatin methacrylate (GelMA) and was dually cross-linked. Using the Box-Behnken design, we explored how varying the ink composition affected fiber formation and shape preservation. By adjusting the polymer ratios, we produced a stable hydrogel with varying responses, from a viscous liquid to a thick gel, and optimized 3D scaffolds that were structurally stable both during and after printing, offering precision and flexibility. Our ink exhibited shear-thinning behavior and high swelling capacity, as well as ECM-like characteristics and biocompatibility, making it an ideal candidate for soft tissues matrices with storage modulus of around 300 Pa. Animal trials and CAM assays confirmed its biocompatibility and integration with host tissue.

Solar-powered and antibacterial water purification via Cu-BTC-embedded reduced graphene oxide nanocomposite aerogels

Advancements in the design of porous active materials for interfacial solar evaporation have shown promise in the development of next-generation solar evaporation active materials that can present a wide range of water-purification properties. In this study, a new class of metal-organic nanoparticles-embedded reduced graphene oxide (rGO) nanocomposite aerogels is developed, with both solar steam generation behavior and antibacterial properties. The self-assembly process is used to introduce Cu-BTC nanoparticles (Cu-BTC NPs) into the structure of rGO aerogels to fabricate Cu-BTC/rGO nanocomposite aerogels. By varying the content of Cu-BTC NPs in the self-assembly precursor solution, the surface area, pore texture, and evaporation rate of samples are altered to reach both high energy conversion efficiency and antibacterial properties. An evaporation rate of 1.13 kg/m2h and an efficiency of 81.8% are achieved when the highest content of Cu-BTC NPs (1 mg/ml) is introduced to the precursor solution. This evaporation efficiency is 32% and 59% higher than that of the rGO aerogel and pure water, respectively. This behavior is related to the surface area and pore size of the nanocomposite aerogels, which increase and decrease with the content of Cu-BTC NPs, respectively. Additionally, the Cu-BTC/rGO aerogel presents antibacterial activity against S. aureus and E. coli. As a result, Cu-BTC/rGO nanocomposite aerogels have great potential as active materials for the design of next-generation solar steam generation systems for the treatment of wastewater contaminated with pathogenic bacteria.

In vitro electrically controlled amoxicillin release from 3D-printed chitosan/bismuth ferrite scaffolds

The goal of this study was to design and fabricate a 3D-printed wound dressing using chitosan as a bioink, with the ability to release the antibiotic drug amoxicillin (AMX) in response to mild electrical stimulation. This was achieved through the incorporation of bismuth ferrite (BFO) nanoparticles, which have both magnetic and ferroelectric properties. The chitosan-based scaffolds containing various concentrations of BFO were analyzed using Fourier transform infrared spectroscopy, and the release of AMX from the scaffolds was evaluated in vitro under electrical stimulation. The results demonstrated that the scaffolds had a suitable structure for drug loading and release, and the release of AMX was successfully controlled by the applied electrical stimulus. The maximum tensile strength (4.97 ± 0.34 MPa) was observed at the ratio of 6% CHT/0.025% BFO scaffolds and the scaffold with 6% CHT/0.075% BFO had the maximum cell viability of (∼130%) at 168 h incubation time. This study highlights the potential of BFO to deliver therapeutic drugs from a 3D-printed chitosan scaffold in a controlled manner.

Bioactive wound dressing based on decellularized tendon and GelMA with incorporation of PDA-loaded asiaticoside nanoparticles for scarless wound healing

In this study, bioactive composite hydrogels were created using the decellularized extracellular matrix (ECM), GelMA, and Polydopamine-loaded Asiaticoside (AC@PDA) nanoparticles for use as wound dressings that could promote healing. A decellularization method was used to obtain ECM from porcine Achilles tendon tissue. AC@PDA nanoparticles were then synthesized and found to have a uniform spherical structure with good cytocompatibility, particularly when compared to PDA nanoparticles alone. The mechanical properties of the bioactive composite hydrogels showed good elasticity and shape recovery after compression, with a slight decrease in compressive strength due to the addition of nanoparticles. The formation of interpenetrating networks through the use of EDC/NHS was also found to improve the mechanical properties and moisture retention of the hydrogels. The PDA/ECM-G and AC@PDA/ECM-G hydrogels showed higher water absorption capacity and similar moist retention capacity to the ECM-G hydrogel. The microstructure of the hydrogels was observed through SEM, with the ECM-G hydrogel showing a dense and compact structure, while the PDA/ECM-G and AC@PDA/ECM-G hydrogels displayed a more porous and interconnected structure due to the presence of nanoparticles. In vitro cytotoxicity tests on human skin fibroblasts showed good biocompatibility for all hydrogels. The in vivo wound healing performance of the hydrogels was also tested on a full-thickness excisional wound model in mice, with the AC@PDA/ECM-G hydrogel showing the fastest wound closure without scarring and the highest-formed hair follicles. The AC@PDA/ECM-G hydrogel had the best performance in promoting wound healing. These results suggest that the bioactive hydrogel has the potential for use as a wound dressing.

Multifunctional nanostructures: Intelligent design to overcome biological barriers

Over the past three decades, nanoscience has offered a unique solution for reducing the systemic toxicity of chemotherapy drugs and for increasing drug therapeutic efficiency. However, the poor accumulation and pharmacokinetics of nanoparticles are some of the key reasons for their slow translation into the clinic. The is intimately linked to the non-biological nature of nanoparticles and the aberrant features of solid cancer, which together significantly compromise nanoparticle delivery. New findings on the unique properties of tumors and their interactions with nanoparticles and the human body suggest that, contrary to what was long-believed, tumor features may be more mirage than miracle, as the enhanced permeability and retention based efficacy is estimated to be as low as 1%. In this review, we highlight the current barriers and available solutions to pave the way for approved nanoformulations. Furthermore, we aim to discuss the main solutions to solve inefficient drug delivery with the use of nanobioengineering of nanocarriers and the tumor environment. Finally, we will discuss the suggested strategies to overcome two or more biological barriers with one nanocarrier. The variety of design formats, applications and implications of each of these methods will also be evaluated.

The effect of the molecular structure of hydroxypropyl methylcellulose on the states of water, wettability, and swelling properties of cryogels prepared with and without CaO2

Hydroxypropyl methylcellulose (HPMC) belongs to the cellulose ether family that has hydroxyl groups substituted by hydrophobic methyl groups (DS) and hydrophilic hydroxypropyl groups (MS). Herein, the interactions between water molecules and cryogels prepared with HPMC in the presence and absence of a linear nonionic surfactant, as well as CaO2 microparticles, which react with water producing O2, were systematically investigated by sorption experiments and Time-Domain Nuclear Magnetic Resonance. Regardless of the DS and MS, most water molecules presented transverse relaxation time t2 typical of intermediate water and a small population of more tightly bound water. HPMC cryogels with the highest DS of 1.9 presented the slowest swelling rate of 0.519 ± 0.053 gwater/(g.s) and the highest contact angle values 85.250o ± 0.004o, providing the best conditions for a slow reaction between CaO2 and water. The presence of surfactant favored hydrophobic interactions that allowed the polar head of the surfactant to be exposed to the medium, resulting in a higher swelling rate and lower contact angle values. The HPMC with the highest MS presented the fastest swelling rate and the lowest contact angle. These findings are relevant for the formulations and reactions, where tuning the swelling kinetics is crucial for the final application.

3D high-precision melt electro written polycaprolactone modified with yeast derived peptides for wound healing

In this study melt electro written (MEW) scaffolds of poly(ε-caprolactone) PCL are decorated with anti-inflammatory yeast-derived peptide for skin wound healing. Initially, 13 different yeast-derived peptides were screened and analyzed using both in vitro and in vivo assays. The MEW scaffolds are functionalized with the selected peptide VLSTSFPPW (VW-9) with the highest activity in reducing pro-inflammatory cytokines and stimulating fibroblast proliferation, migration, and collagen production. The peptide was conjugated to the MEW scaffolds using carbodiimide (CDI) and thiol chemistry, with and without plasma treatment, as well as by directly mixing the peptide with the polymer before printing. The MEW scaffolds modified using CDI and thiol chemistry with plasma treatment showed improved fibroblast and macrophage penetration and adhesion, as well as increased cell proliferation and superior anti-inflammatory properties, compared to the other groups. When applied to full-thickness excisional wounds in rats, the peptide-modified MEW scaffold significantly enhanced the healing process compared to controls (p < 0.05). This study provides proof of concept for using yeast-derived peptides to functionalize biomaterials for skin wound healing.

Carbon nanotubes as a nitric oxide nano-reservoir improved the controlled release profile in 3D printed biodegradable vascular grafts

Abstract Small diameter vascular grafts (SDVGs) are associated with a high failure rate due to poor endothelialization. The incorporation of a nitric oxide (NO) releasing system improves biocompatibility by using the NO effect to promote endothelial cell (EC) migration and proliferation while preventing bacterial infection. To circumvent the instability of NO donors and to prolong NO releasing, S -nitroso- N -acetyl- d -penicillamine (SNAP) as a NO donor was loaded in multi-walled carbon nanotubes (MWCNTs). Successful loading was confirmed with a maximum SNAP amount of ~ 5% (w/w) by TEM, CHNS analysis and FTIR spectra. SDVGs were 3D printed from polycaprolactone (PCL) and coated with a 1:1 ratio of polyethylene glycol and PCL dopped with different concentrations of SNAP-loaded matrix and combinations of MWCNTs-OH. Coating with 10% (w/w) SNAP-matrix-10% (w/w) SNAP-MWCNT-OH showed a diminished burst release and 18 days of NO release in the range of 0.5-4 × 10 -10  mol cm −2  min −1 similar to the NO release from healthy endothelium. NO-releasing SDVGs were cytocompatible, significantly enhanced EC proliferation and migration and diminished bacterial viability. The newly developed SNAP-loaded MWCNT-OH has a great potential to develop NO releasing biomaterials with a prolonged, controlled NO release promoting in-situ endothelialization and tissue integration in vivo , even as an approach towards personalized medicine.

Porcupine-inspired microneedles coupled with an adhesive back patching as dressing for accelerating diabetic wound healing

Diabetes chronic wound is a severe and frequently occurring medical issue in patients with diabetes that often leads to more serious complications. Microneedles (MNs) can be used for wound healing as they can effectively pierce the epidermis and inject drugs into the wound tissue. However, common MN patches cannot provide sufficient skin adhesion to prevent detachment from the wound area. Inspired by the barb hangnail microstructure of porcupine quills, a porcupine quill-like multilayer MN patch with an adhesive back patching for tissue adhesion and diabetic wound healing was designed. Sodium hyaluronate-modified CaO2 nanoparticles and metformin (hypoglycemic agent) were loaded into the polycaprolactone tips of MNs, endowing them with exceptional antibacterial ability and hypoglycemic effect. A flexible and adhesive back patching was formed by polyacrylamide-polydopamine/Cu2+ composite hydrogel, which ensures that the MN patches do not peel off from the application sites and reduce bacterial infection. The bioinspired multilayer structure of MN patches exhibits satisfactory mechanical and antibacterial properties, which is a potential multifunctional dressing platform for promoting wound healing. Statement of significance: The porcupine quill-like microneedles (MNs) with PAM-PDA/Cu2+ (PPC) composite hydrogel back patching have been fabricated, which can enhance the adhesion property of MNs to the skin through a physical interlock of multilayer MNs and chemical bonding of hydrogel patching. CaO2-HA NPs and metformin were loaded into the polycaprolactone tips of MNs, endowing them with the exceptional antibacterial ability and hypoglycemic effect, which could accelerate diabetic wound healing. As a safe and effective strategy in transdermal delivery of drugs, the as-fabricated flexible multilayer MN patch with good antibacterial, hypoglycemic, and biocompatibility has been used to promote the healing of diabetic wound by releasing oxygen and inhibiting inflammation at the wound site.

Regenerated silk fibroin and alginate composite hydrogel dressings loaded with curcumin nanoparticles for bacterial-infected wound closure

It is important to treat a bacterial-infected wound with a hydrogel dressing due to its excellent biocompatibility and extracellular matrix mimicking structure. In this work, the antibacterial curcumin nanoparticles (Cur-NPs) loaded silk fibroin and sodium alginate (SF/SA) composite hydrogels have been developed as dressings for bacterial-infected wound closure. The as-prepared composite hydrogel dressings exhibited excellent biocompatibility and antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in vitro. In addition, the composite hydrogel dressings showed good tissue adhesive strength because of their high viscosity and abundance of amino groups distributed on SF, which can form multi-aldehyde polysaccharides with the tissue surface. The porous 3D structure of the composite hydrogel dressings facilitated the absorption of exudate from the wound site and promoted the fusion of cellular nutrients and metabolites. In the full-thickness skin defect model with and without bacterial infection, the Cur-NPs loaded SF/SA composite hydrogel dressings prominently improves the closure of bacterial-infected wounds by improving cell proliferation, anti-inflammatory properties, vascular remodeling, and collagen deposition.

Waste valorization as low-cost media engineering for auxin production from the newly isolated Streptomyces rubrogriseus AW22: Model development

Indole-3-acetic acid (IAA) represents a crucial phytohormone regulating specific tropic responses in plants and functions as a chemical signal between plant hosts and their symbionts. The Actinobacteria strain of AW22 with high IAA production ability was isolated in Algeria for the first time and was characterized as Streptomyces rubrogriseus through chemotaxonomic analysis and 16 S rDNA sequence alignment. The suitable medium for a maximum IAA yield was engineered in vitro and in silico using machine learning-assisted modeling. The primary low-cost feedstocks comprised various concentrations of spent coffee grounds (SCGs) and carob bean grounds (CBGs) extracts. Further, we combined the Box-Behnken design from response surface methodology (BBD-RSM) with artificial neural networks (ANNs) coupled with the genetic algorithm (GA). The critical process parameters screened via Plackett-Burman design (PBD) served as BBD and ANN-GA inputs, with IAA yield as the output variable. Analysis of the putative IAA using thin-layer chromatography (TLC) and (HPLC) revealed Rf values equal to 0.69 and a retention time of 3.711 min, equivalent to the authentic IAA. AW 22 achieved a maximum IAA yield of 188.290 ± 0.38 μg/mL using the process parameters generated by the ANN-GA model, consisting of L-Trp, 0.6%; SCG, 30%; T°, 25.8 °C; and pH 9, after eight days of incubation. An R2 of 99.98%, adding to an MSE of 1.86 × 10−5 at 129 epochs, postulated higher reliability of ANN-GA-approach in predicting responses, compared with BBD-RSM modeling exhibiting an R2 of 76.28%. The validation experiments resulted in a 4.55-fold and 4.46-fold increase in IAA secretion, corresponding to ANN-GA and BBD-RSM models, respectively, confirming the validity of both models.

Bioceramics/Electrospun Polymeric Nanofibrous and Carbon Nanofibrous Scaffolds for Bone Tissue Engineering Applications

Bone tissue engineering integrates biomaterials, cells, and bioactive agents to propose sophisticated treatment options over conventional choices. Scaffolds have central roles in this scenario, and precisely designed and fabricated structures with the highest similarity to bone tissue have shown promising outcomes. On the other hand, using nanotechnology and nanomaterials as the enabling options confers fascinating properties to the scaffolds, such as precisely tailoring the physicochemical features and better interactions with cells and surrounding tissues. Among different nanomaterials, polymeric nanofibers and carbon nanofibers have attracted significant attention due to their similarity to bone extracellular matrix (ECM) and high surface-to-volume ratio. Moreover, bone ECM is a biocomposite of collagen fibers and hydroxyapatite crystals; accordingly, researchers have tried to mimic this biocomposite using the mineralization of various polymeric and carbon nanofibers and have shown that the mineralized nanofibers are promising structures to augment the bone healing process in the tissue engineering scenario. In this paper, we reviewed the bone structure, bone defects/fracture healing process, and various structures/cells/growth factors applicable to bone tissue engineering applications. Then, we highlighted the mineralized polymeric and carbon nanofibers and their fabrication methods.

Maillard Reaction Crosslinked Alginate-Albumin Scaffolds for Enhanced Fenofibrate Delivery to the Retina: A Promising Strategy to Treat RPE-Related Dysfunction

There are limited treatments currently available for retinal diseases such as age-related macular degeneration (AMD). Cell-based therapy holds great promise in treating these degenerative diseases. Three-dimensional (3D) polymeric scaffolds have gained attention for tissue restoration by mimicking the native extracellular matrix (ECM). The scaffolds can deliver therapeutic agents to the retina, potentially overcoming current treatment limitations and minimizing secondary complications. In the present study, 3D scaffolds made up of alginate and bovine serum albumin (BSA) containing fenofibrate (FNB) were prepared by freeze-drying technique. The incorporation of BSA enhanced the scaffold porosity due to its foamability, and the Maillard reaction increased crosslinking degree between ALG with BSA resulting in a robust scaffold with thicker pore walls with a compression modulus of 13.08 KPa suitable for retinal regeneration. Compared with ALG and ALG-BSA physical mixture scaffolds, ALG-BSA conjugated scaffolds had higher FNB loading capacity, slower release of FNB in the simulated vitreous humour and less swelling in water and buffers, and better cell viability and distribution when tested with ARPE-19 cells. These results suggest that ALG-BSA MR conjugate scaffolds may be a promising option for implantable scaffolds for drug delivery and retinal disease treatment.

MSCs-laden silk Fibroin/GelMA hydrogels with incorporation of platelet-rich plasma for chondrogenic construct

Repair of osteochondral defects and regeneration of cartilage is a major challenge. In this work, the mesenchymal stem cells (MSCs)-laden hydrogel was designed using silk fibroin (SF) and gelatin methacrylate (GelMA), to encapsulate platelet-rich plasma (PRP). Initially, GelMA was synthesized, and SF was prepared using silkworm cocoon, then MSCs-laden SF/GelMA (SG) hydrogel was fabricated. The physicochemical properties of the hydrogels were evaluated using Fourier-transform infrared spectroscopy, scanning electron microscope, and rheometry. After hydrogel preparation, the viability of MSCs in the hydrogels was investigated via CCK-8 analysis and fluorescent images. The MSCs-laden SG hydrogel containing PRP was subsequently injected into the cartilage defect area in Sprague Dawley rats. Hematoxylin and eosin (H&E), Masson staining, and Mankin scores evaluation confirmed the new cartilage formation in 8 weeks. The results presented in the study, therefore, showed that the prepared MSCs-laden SG hydrogel loaded with PRP has the potential for cartilage reconstruction, which is crucial to the treatment of knee osteoarthritis.

Improved anti-inflammatory properties of xanthan gum hydrogel physically and chemically modified with yeast derived peptide

Abstract Bioactive peptides from natural resources with associated beneficial biological properties such as skin wound healing have drawn much attention. Polysaccharides with their biocompatibility, biodegradability, and ease of modification are suitable carriers for peptides delivery to the wound. In this study, a polysaccharide-peptide system was designed for potential wound healing applications. Xanthan hydrogels were modified with the yeast-derived peptide VW-9 with known biological properties via chemical conjugation using carbodiimide chemistry (XG-g-VW-9) or physically incorporation (XG-p-VW-9). Grafting VW-9 to the hydrogels increased the hydrogels' swelling degree and the release of the peptide from the hydrogels followed the Higuchi model indicating the peptide diffusion from the hydrogel matrix without hydrogel matrix dissolution. Both hydrogels were cytocompatible toward the tested fibroblast and macrophage cells. XG-p-VW-9 and XG-g-VW-9 reduce the level of tumor necrosis factor-alpha and interleukin-6 in cells activated with lipopolysaccharide more efficiently than free VW-9. Thus, VW-9-modified xanthan hydrogels may have the potential to be considered for skin wound healing.

Fabrication and desired properties of conductive hydrogel dressings for wound healing

Conductive hydrogels are recognized as promising materials for wound healing. Valuable properties of conductive hydrogels suggest the possibility of their use as an alternative wound dressing to traditional dressings such as bandages.

Technoeconomic Assessment of Biopolymer Production from Crustacean Waste with the UK as a Case Study

Marine pollution has increased in recent decades, largely due to the proliferation of seafood processing plants and the improper disposal of their associated waste streams. The waste streams consist mainly of shells that are composed of chitin, which is the most abundant aminopolysaccharide biopolymer in nature. Recognizing the value of chitin, the potential for the valorization of crustacean waste for chitin production was explored. In this regard, biogenic crab waste was subjected to chemical-only, enzymatic-chemical, and microbial treatments for chitin production. The results were employed as inputs for process simulation as a precursor to undertaking performance assessments. This study subsequently showed that the net present values (NPVs) of the chemical-only, enzyme-chemical, and microbial chitin production pathways were GBP 118.63 million, GBP 115.67 million, and GBP 132.34 million, respectively, indicating that the microbial chitin production pathway constituted the most appropriate technology for future investment. Employing a cost-benefit (CB) analysis, the CB ratios for the chemical-only, enzymatic-chemical, and microbial approaches were determined to be 7.31, 0.45, and 0.23, respectively. These results reinforced the dominant status of the microbial approach for chitin production from crab waste as the preferred valorization strategy. This study was able to provide information regarding the implications of executing alternative scenarios for crustacean waste.

Injectable, self-healing, transparent, and antibacterial hydrogels based on chitosan and dextran for wound dressings

One major shortcoming of biopolymeric based wound dressing so far is the lack of an integrated multi-functional system that could provide suitable mechanical strength, fast self-healing, transparency, antibacterial and antioxidant effects. Benefiting from the dynamic and rapid reaction between glycidyl trimethyl ammonium chloride-graft- chitosan (QCS) and aldehyde-dextran (ODex) under physiological conditions, we designed hydrogels (QCS-ODex) with fast in situ gel-forming (< 70 s), porous structure (300-350 μm), stable storage modulus and the loss modulus, suitable swelling capacity (2.465 folds of chitosan), tissue adhesion, transmission property, free radical scavenging capacity, good self-healing behavior, and injectability, inherent antibacterial (against E. coli and S. aureus) and biocompatibility. Furthermore, Baicalein could be in situ encapsulated into QCS-ODex hydrogels, and the release behavior of Baicalein could be regulated by adjusting the ratio of QCS and ODex. The Baicalein-loaded QCS-ODex hydrogel further facilitated free radical scavenging and antibacterial bioactivities due to the cooperative therapeutic effects between QCS-ODex and Baicalein. This study may provide new insights into designing multi-functional QCS-ODex hydrogels with multiple therapeutic effects as a wound dressing.

Fabrication, characterization and biological properties evaluation of bioactive scaffold based on mineralized carbon nanofibers

Tissue engineering as an innovative approach aims to combine engineering, biomaterials and biomedicine to eliminate the drawbacks of conventional bone defect treatment. In the current study, we fabricated bioengineered electroactive and bioactive mineralized carbon nanofibers as the scaffold for bone tissue engineering applications. The scaffold was fabricated using the sol-gel method and thoroughly characterized by SEM imaging, EDX analysis and a 4-point probe. The results showed that the CNFs have a diameter of 200 ± 19 nm and electrical conductivity of 1.02 ± 0.12 S cm−1. The in vitro studies revealed that the synthesized CNFs were osteoactive and supported the mineral crystal deposition. The hemolysis study confirmed the hemocompatibility of the CNFs and cell viability/proliferation sassy using an MTT assay kit showed the proliferative activities of mineralized CNFs. In conclusion, this study revealed that the mineralized CNFs synthesized by the combination of sol-gel and electrospinning techniques were electroactive, osteoactive and biocompatible, which can be considered an effective bone tissue engineering scaffold. Communicated by Ramaswamy H. Sarma.

Reinforced conductive polyester based on itaconic acids, glycerol and polypyrrole with potential for electroconductive tissue restoration

Modified chemically crosslinked polyesters as soft and electroconductive materials have investigated for tissue engineering applications. In this work, electroconductivity, thermal stability, and mechanical properties of synthesized Poly (glycerol-sebacate-itaconic) (PGSIT) by the solvent-free method was studied by incorporating polypyrrole (PPy) and clay within the PGSIT matrix. Hydrogen bonds between PGSIT and PPy lead to a homogeneous dispersion of clay and PPy within the PGSIT matrix. The evaluations indicated that PPy and clay could raise the conductivity of PGSIT from 5.9 × 10−11 S/cm to 1.4 × 10−4 S/cm, Young's modulus from 0.19 MPa to 0.9 MPa, tensile strain to 0.91 MPa from 0.25 MPa, and improved the thermal stability and hydrophilicity of the matrix. The PGSIT-PPy-clay composite might have the potential as electroconductive bio-elastomer in tissue engineering applications.

Transdermal delivery of allopurinol on acute hyperuricemic mice via polymer microneedles for regulation of serum uric acid levels

Allopurinol (AP) is widely used to treat hyperuricemia which may cause severe side effects after oral administration. Alternative means for the treatment of hyperuricemia are demanded to simultaneously facilitate drug...

Chemical Composition, Antioxidant Activity and Cytocompatibility of Polyphenolic Compounds Extracted from Food Industry Apple Waste: Potential in Biomedical Application

Apple pomace (AP) from the food industry is a mixture of different fractions containing bioactive polyphenolic compounds. This study provides a systematic approach toward the recovery and evaluation of the physiochemical and biological properties of polyphenolic compounds from AP. We studied subcritical water extraction (SCW) and solvent extraction with ethanol from four different AP fractions of pulp, peel, seed, core, and stem (A), peel (B), seed and core (C), and pulp and peel (D). The subcritical water method at the optimum condition resulted in total polyphenolic compounds (TPC) of 39.08 ± 1.10 mg GAE per g of AP on a dry basis compared to the ethanol extraction with TPC content of 10.78 ± 0.94 mg GAE/g db. Phloridzin, chlorogenic acid, and quercetin were the main identified polyphenolics in the AP fractions using HPLC. DPPH radical scavenging activity of fraction B and subcritical water (SW) extracts showed comparable activity to ascorbic acid while all ethanolic extracts were cytocompatible toward human fibroblast (3T3-L1) and salivary gland acinar cells (NS-SV-AC). Our results indicated that AP is a rich source of polyphenolics with the potential for biomedical applications.

Printable hyaluronic acid hydrogel functionalized with yeast-derived peptide for skin wound healing

Targeted delivery of bioactive agents, growth factors, and drugs to skin wounds is a growing trend in biomaterials development for wound healing. This study presents a printable hyaluronic acid (HA) based hydrogel to deliver yeast-derived ACE-inhibitory peptide of VLSTSFPPW (VW-9) to the wound site. We first conjugated tyramine (Ty) on the carboxyl groups of the HA to form a phenol-functionalized HA (HA-Ty); then, the carboxylic acid groups of HA-Ty were aminated with ethylenediamine (HA-Ty-NH2). The primary amine groups of the HA-Ty-NH2 could then react with the carboxylic acids of the peptide. The hydrogel was then 3D printed and crosslinked with visible light. The modification of HA was confirmed by 1H NMR and FTIR. The swelling capacity of the conjugated hydrogels was 1.5-fold higher compared to the HA-Ty-NH2 hydrogel. The conjugated peptide did not affect on rheological properties and morphology of the hydrogels. The 3T3-L1 fibroblast cells seeded on the peptide-modified hydrogels exhibited higher viability than the hydrogels without the peptide, indicating that the peptide-enriched hydrogels may have the potential for wound healing applications.

Biorefining of corn stover for efficient production of bioethanol, biodiesel, biomethane, and value-added byproducts

The present study investigated an integrated biorefinery that employed corn stover as the feedstock for sustainable bioethanol, biodiesel, biogas, chitosan, glycerol, and animal feed production. Corn stover was initially subjected to dilute acid pretreatment (1.8 % v/v H2SO4, 121 °C, and 22 min) followed by enzymatic hydrolysis with a commercial cellulase (37 °C, 72 h) to promote the release of glucose (∼93 wt%) and xylose (∼89 wt%). Mucor indicus fungus was then employed to convert the released sugars into bioethanol, glycerol, and fungal biomass with yields of 0.38 g g−1, 36 mg g−1, and 0.51 g g−1, respectively. The biomass of M. indicus was processed to extract chitosan (6 mg g−1 fungal biomass) and lipids (297 mg g−1 fungal biomass). The lipid was subsequently converted to biodiesel via transesterification in the presence of HCl/ MeOH with the yield of 0.54 g g−1 fungal lipid. The defatted biomass residue was then converted to biogas with 81 % theoretical yield through anaerobic digestion. To ensure process circularity, the nutritional values of pretreated and hydrolyzed corn stover were also investigated with their suitability as livestock. It was determined that 158.1 thousand tons of dry corn stover, which was annually collectible in Iran, could be used for the production of 137.6 kg chitosan, 10.4 ton animal feed, 870.0 kg glycerol, 40.7 million litters ethanol, 2.8 million m3 biodiesel, and 449.2 million m3 biomethane. The utilization of the produced ethanol, biodiesel, and biomethane in transporting sector was shown to have the potential of facilitating 4.3 million tons of equivalent carbon dioxide and a 197.8 million dollars reduction of associated social costs.

Evaluation of two fungal exopolysaccharides as potential biomaterials for wound 2 healing applications

Microbial exopolysaccharides (EPSs) are mostly produced by bacteria and fungi and have potential use in the production of biomedical products such as nutraceuticals and in tissue engineering applications. The present study investigated the in vitro biological activities and in vivo wound healing effects of EPSs produced from a Sclerotium-forming fungus (Sclerotium glucanicum DSM 2159) and a yeast (Rhodosporidium babjevae), denoted as scleroglucan (Scl) and EPS-R, respectively. EPS yields of 0.9 ± 0.07 g/L and 1.11 ± 0.4 g/L were obtained from S. glucanicum and R. babjevae, respectively. The physicochemical properties of the EPSs were characterized using infrared spectroscopy and scanning electron microscopy. Further investigations of the biological properties showed that both EPSs were cytocompatible toward the human fibroblast cell line and demonstrated hemocompatibility. Favorable wound healing capacities of the EPSs (10 mg/mL) were also established via in vivo tests. The present study therefore showed that the EPSs produced by S. glucanicum and R. babjevae have the potential use as biocompatible components for the promotion of dermal wound healing.

“Fabrication of bioactive polyphenolic biomaterials for bone tissue engineering”

Bone disorders constitute a major problem for public health worldwide. Bone tissue engineering (BTE), which involves the fabrication of a bioactive bone scaffold has provided an effective solution for this global issue. Polyphenolic compound (PPC) as a bioactive molecule can be incorporated into the bone scaffold to promote the bone recovery process. This is because PPCs are recognized as having the potential to enhance the proliferation, migration, and differentiation of bone cells and hydroxyapatite (HA) mineralization for bone formation. In addition, PPCs possess antioxidant, anti-inflammatory, and antibacterial properties, making them effective biomolecules for bone tissue regeneration. Furthermore, the presence of PPCs in easily available and low-cost food and agricultural wastes, with desirable biological characteristics, has promoted an increasing interest in their isolation and further exploitation in tissue engineering. However, the opportunities for the exploration of the PPCs from food and agricultural wastes for their utilization in BTE have not been comprehensively explored and studied. There is, therefore, a necessity to highlight the potential of waste-derived PPCs as a high-value biomass source for employment in BTE. This review discusses the effective applications of PPCs for the fabrication of different polyphenol-functionalized scaffolds for BTE applications. Furthermore, fruit wastes' potential for the extraction of PPCs with various biological activities is discussed. It is anticipated that this review will help to improve the design and preparation of the next generation of bioactive bone scaffolds, using the fruit waste-derived PPCs.

2022

Biosynthesis of exopolysaccharide from waste molasses using Pantoea sp. BCCS 001 GH: a kinetic and optimization study

The bacterium Pantoea sp. BCCS 001 GH produces an exopolysaccharide (EPS) named Pantoan through using sugar beet molasses (SBM) as an inexpensive and widely available carbon source. This study aims to investigate the kinetics and optimization of the Pantoan biosynthesis using Pantoea sp. BCCS 001 GH in submerged culture. During kinetics studies, the logistic model and Luedeking-Piret equation are precisely fit with the obtained experimental data. The response surface methodology (RSM)-central composite design (CCD) method is applied to evaluate the effects of four factors (SBM, peptone, Na2HPO4, and Triton X-100) on the concentration of Pantoan in batch culture of Pantoea sp. BCCS 001 GH. The experimental and predicted maximum Pantoan production yields are found 9.9 ± 0.5 and 10.30 g/L, respectively, and the best prediction factor concentrations are achieved at 31.5 g/L SBM, 2.73 g/L peptone, 3 g/L Na2HPO4, and 0.32 g/L Triton X-100 after 48 h of submerged culture fermentation, at 30 °C. The functional groups and major monosaccharides (glucose and galactose) of a purified Pantoan are described and confirmed by 1HNMR and FTIR. The produced Pantoan is also characterized by thermogravimetric analysis and the rheological properties of the biopolymer are investigated. The present work guides the design and optimization of the Pantoea sp. BCCS 001 GH culture media, to be fine-tuned and applied to invaluable EPS, which can be applicable in food and biotechnology applications.

Graphene oxide-reinforced alginate/gelatin hydrogel via Schiff-base bond and thiol-Michael addition for bone regeneration

The poor mechanical properties of hydrogels limit their application as scaffolds to provide support for bone regeneration. Inspired by the superior mechanical properties of nanocomposites-reinforced hydrogels and the double network (DN) structure of hydrogels, the current study investigated the fabrication of graphene oxide (GO) reinforced DN hydrogels for bone regeneration. To this regard, aldehyde methylene sodium alginate (AMSA), amino gelatin (aminoG), and dithiothreitol modified graphene oxide (DGO) were initially synthesized, and subsequently were employed in the preparation of AMSA/aminoG (AG) and DGO/AMSA/aminoG (GSG) DN-hydrogels, while imposing different mass ratios of the reacting components. The physicochemical and biological properties of the prepared hydrogels were subsequently assessed using several tests such as Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, nuclear magnetic resonance, cell compatibility and in vivo experiments. The compressive strengths of the prepared AG and GSG hydrogels were conversely correlated with their porosity characteristics. This study showed that although AG and GSG hydrogels had favorable cell viability and cell proliferation characteristics, GSG hydrogels presented an improved osteogenic capacity compared to AG hydrogels. This study was, therefore, able to demonstrate the functionality of employing novel GSG hydrogels in tissue engineering via their use as scaffolds for mechanical support and cell proliferation to promote bone regeneration.

Transdermal delivery of allopurinol to acute hyperuricemic mice via polymer microneedles for the regulation of serum uric acid levels

Allopurinol (AP) is widely used to treat hyperuricemia which may cause severe side effects upon oral administration. Alternative means for the treatment of hyperuricemia are demanded to simultaneously facilitate drug absorption, patient compliance, and fewer side effects. In this study, a new polymer microneedle (MN) system was developed for the transdermal delivery of AP to acute hyperuricemic mice. This study aims to achieve the controllable regulation of serum uric acid (SUA) levels with fewer side effects compared with oral administration. The matrix of polymer MNs consisted of polyvinylpyrrolidone (PVP) and polycaprolactone (PCL), in which the rapid dissolution of PVP offers a rapid dissolution of AP into the blood and the biodegradability of PCL resulting in a sustainable drug release behavior. An in vivo study demonstrated that the AP-loaded MN system can effectively reduce the SUA levels as oral administration with lower side effects, which will be conducive to reducing the adverse reactions and improving the bioavailability of AP. This MN-mediated strategy can facilitate transcutaneous hyperuricemia treatment and provide a new alternative for the exploration of clinical treatment of hyperuricemia and improvement of patient compliance.

Technoeconomic and Environmental Assessment of Alternative Biorefineries for Bioenergy and Polyphenolic Production from Pomace Biomass

Pomace is generated during fruit processing and is regarded as a highly polluting waste stream due to its high moisture content, biological instability, and acidic properties. To facilitate pomace management, this study has applied the biorefinery concept to develop systems that facilitate value extraction. To this regard, alternative scenarios for the production of polyphenolic compounds and bioenergy from apple pomace were investigated using ASPEN Plus for process modeling, simulation, and analysis. Systems facilitating the production of polyphenols via the use of the green solvents (i.e. subcritical water in scenario (a) and ethanol in scenario (b)), while also co-producing bioenergy, were compared to a system that produced only bioenergy (i.e. scenario (c)). Comparisons of profitabilities and environmental performances were achieved via considerations of the net present values (NPVs) and potential environmental impacts (PEIs) of all scenarios. The study was able to show that scenario (a) constituted the only economically viable strategy, with a NPV of US$ 19.86 million, while scenarios (b) and (c) were determined to have NPVs of US$ − 88.12 million and US$ − 4.05 million respectively. Scenario (b) was also determined to have the poorest environmental performance with a PEI of 148 kPEI/h. Notably, although scenario (c) (PEI of 0.21 kPEI/h) was determined to present a better environmental performance than scenario (a) (PEI of 47 kPEI/h), its economic infeasibility indicated that it will be impractical to consider it as a viable pomace valorization strategy in a scaled-up system. This study therefore proposed that scenario (a) may constitute a preferred pomace valorization strategy provided technological innovations, i.e., use of alternative energy sources and gas filters, are explored to reduce the major existing challenge of enhanced global warming potential due to greenhouse gas emissions. This study therefore provides information regarding the sustainability implication of executing different biorefinery scenarios for pomace management in the fruit processing industry. Graphical abstract: [Figure not available: see fulltext.]

Enzymatically crosslinked hydrogel based on tyramine modified gelatin and sialylated chitosan

Abstract The enzymatically crosslinked hydrogel could replicate the cellular microenvironment for biomedical applications. In the present study, to improve the cytocompatibility of chitosan (CS), sialic acid (SA) was introduced to CS to synthesize sialylated CS (CS-SA), and the tyramine (TA) was grafted to gelatin (G) to obtain TA modified gelatin (G-TA). The successful synthesis of CS-SA and G-TA was confirmed using 1 H NMR and UV-Vis absorption spectra. The interpenetrating polymer networks G-TA/CS-SA (GC) hydrogel was then fabricated via blending G-TA and CS-SA solutions and crosslinked using horseradish peroxidase. The storage modulus (G′) of the fabricated GC hydrogels with different ratios of G-TA/CS-SA greatly varied during the formation and strain of hydrogels. With the increase of CS-SA concentration from 0% to 2%, the storage modulus of GC hydrogels was also observed to decrease from 1500 Pa to 101 Pa; the water uptake capacity of GC hydrogels increased from 1000% to 4500%. Additionally, the cell counting kit-8 and fluorescent images demonstrated the excellent cytocompatibility of GC hydrogels after culturing with NIH 3T3 cells. The obtained results indicated that the fabricated GC hydrogels might have potential in biomedical fields, such as wound dressing.

Synthesis, surface modifications, and biomedical applications of carbon nanofibers: Electrospun vs vapor-grown carbon nanofibers

Engineered nanostructures are materials with promising properties, enabled by precise design and fabrication, as well as size-dependent effects. Biomedical applications of nanomaterials in disease-specific prevention, diagnosis, treatment, and recovery monitoring require precise, specific, and sophisticated approaches to yield effective and long-lasting favorable outcomes for patients. In this regard, carbon nanofibers (CNFs) have been indentified due to their interesting properties, such as good mechanical strength, high electrical conductivity, and desirable morphological features. Broadly speaking, CNFs can be categorized as vapor-grown carbon nanofibers (VGCNFs) and carbonized CNFs (e.g., electrospun CNFs), which have distinct microstructure, morphologies, and physicochemical properties. In addition to their physicochemical properties, VGCNFs and electrospun CNFs have distinct performances in biomedicine and have their own pros and cons. Indeed, several review papers in the literature have summarized and discussed the different types of CNFs and their performances in the industrial, energy, and composites areas. Crucially however, there is room for a comprehensive review paper dealing with CNFs from a biomedical point of view. The present work therefore, explored various types of CNFs, their fabrication and surface modification methods, and their applications in the different branches of biomedical engineering.

New trends in biotechnological applications of photosynthetic microorganisms

As a source of several valuable products, photosynthetic microorganisms (microalgae and cyanobacteria) have many applications in biomedical, electrochemical, and urban-space fields. Microalgal and cyanobacterial (photoautotrophs) implementations have been the subject matter of several reviews, which mainly focused on exploring effective methods of their harvesting, optimal cultivation conditions, energy conversion efficiency, and new strategies for microalgal health-promoting compound recovery. This review highlights recent investigations into biomedical, urban, environmental, and electrical engineering microalgae and cyanobacteria applications over the last seven years. A brief historical outline of advances in photoautotroph-based technologies is presented prior to an exploration of the important role of these microorganisms in combating global warming and food and energy insecurity. Special attention is given to the photosynthetic oxygen production of algae and the possibility of treating hypoxia-associated diseases such as cancer or tissue injuries. Photoautotroph applications in microrobotics, drug delivery and wound healing systems, biosensors, and bioelectronics are also introduced and discussed. Finally, we present emerging fabrication techniques, such as additive manufacturing, that unleash the full potential of autotrophic, self-sufficient microorganisms at both the micro- and macroscales. This review constitutes an original contribution to photoautotroph biotechnology and is thought to be impactful in determining the future roles of microalgae and cyanobacteria in medical, electrical, or urban space applications.

Mercaptolated chitosan/methacrylate gelatin composite hydrogel for potential wound healing applications

In this study, medical hydrogels (TGs) were fabricated based on thiolate-modified chitosan (TCS) and methacrylate gelatin (GelMA) using the Thiol-Michael addition reaction. The hydrogels were formed via the Michael reaction between TCS and GelMA and determined to have an equilibrium swelling rate of more than 1100% while simultaneously providing a moist environment for the wound, and limiting crust formation. The porosity of the prepared hydrogel was also shown to have a positive correlation with the concentration of the thiolated chitosan in the formulation. A positive correlation between hydrogel strain and stress properties and increasing concentrations of thiolated chitosan was also observed. The cytocompatibility of the prepared hydrogels was also tested and confirmed using CCK-8 assay after 5 days of culture, and the best antimicrobial properties were observed with the hydrogel containing TCS and GelMA in the mass ratio of 1:2. The present study was, therefore, able to highlight the potential of a simple and low-cost approach to developing cytocompatible hydrogels with antibacterial properties and tunable mechanical properties based on the well-studied GelMA. This study implies that the produced hydrogels can have future applications in fabricating skin wound healing dressings.

Tannic acid post-treatment of enzymatically crosslinked chitosan-alginate hydrogels for biomedical applications

Enzyme-mediated crosslinked hydrogels as soft materials for biomedical applications have gained considerable attention. In this article, we studied the effect of tannic acid post-treatment on adhesiveness and physiochemical properties of an enzymatically crosslinked hydrogel based on chitosan and alginate. The hydrogels were soaked in TA solution at different pH (3, 5.5, 7.4, and 9) and concentrations (1, 10, 20, 30 TA wt%). Increasing the TA concentration to 30 TA wt% and pH (up to 7.4) increased the TA loading and TA release. TA post-treatment reduced the swelling ratio and degradation rate of the hydrogels due to the formation of hydrogen bonding between TA molecules, chitosan, and alginate chains resulted in higher crosslinking density. TA-reinforced hydrogels with 30 % TA (Gel-TA 30) exhibited significantly high adhesive strength (up to 18 kPa), storage modulus (40 kPa), and antioxidant activity (>96 %), antibacterial activity, and proliferation and viability of 3 T3-L1 fibroblast cells.

Thermochemical Liquefaction of Pomace Using Sub/Supercritical Ethanol: an Integrated Experimental and Preliminary Economic Feasibility Study

Fossil sourced chemicals such as aromatics, are widely employed in the chemical industry for the production of commodity items. Recognizing the un-sustainability of existing approaches in the production of these chemicals, the current study investigated the valorization of apple pomace (AP) for their production. The present study assessed AP valorization by imposing variations in processing conditions of temperature (100-260 °C), time (0.5-12 h), alcohol/water ratio v/v (0:1-1:0), and Fe3+/H2O2 molar ratio (10:1-100-1), in accordance to the Box-Behnken experimental design. The optimal yield of the oil was 24.6 wt.%, at the temperature, time, alcohol/water ratio v/v, and Fe3+/H2O2 molar ratio of 260 °C, 4.7 h, 1, and 100, respectively. Notably, the application of gas chromatography-mass spectroscopy showed that the oil product contained mainly aromatics and interestingly also alkanes, indicating that the experimental conditions imposed promoted secondary hydrogenation reactions of oxygen-containing species during AP valorization. A consideration of the comparative economics of the proposed AP valorization and the existing AP management approach, using approximate estimation techniques, highlighted the potential of a ~ 59% reduction in the unit cost of AP management. The study therefore presents a compelling basis for future investigations into AP waste management using the thermochemical liquefaction technology. Graphical abstract: [Figure not available: see fulltext.].

Magnesium-doped biphasic calcium phosphate nanoparticles with incorporation of silver: Synthesis, cytotoxic and antibacterial properties

The development of new calcium phosphate nanoparticles with excellent cytocompatibility and antibacterial properties is generating substantial interest in the biomedical field. In this regard, the present study demonstrated the synthesis of magnesium-doped biphasic calcium phosphate nanoparticles containing silver (AgMgB-NPs) via the employment of the chemical wet-precipitation method. Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and ultraviolet-visible spectroscopy (UV-Vis) methods were used to confirm the successful synthesis of AgMgB-NPs. X-ray photoelectron spectroscopy (XPS) and Raman spectra indicated that Mg2+ was doped at the Ca2+ position. The excellent cytocompatibility of AgMgB-NPs was confirmed using the cell counting kit-8 (CCK-8) analysis which employed a culture of human bone marrow-derived mesenchymal stem cells (hBMSCs). Additionally, the antibacterial activity of AgMgB-NPs was evaluated using Gram-negative E. coli and Gram-positive S. aureus micro-organisms. The present study therefore developed novel calcium phosphate nanoparticles that were demonstrated to have the potential for biomedical applications.

Editorial: Advances in protein-based biomaterials for tissue engineering

The Circular Economy Paradigm: Modification of Bagasse-Derived Lignin as a Precursor to Sustainable Hydrogel Production

There have been many efforts to valorise lignin to produce bio-based chemicals and advanced materials. In this study, alkaline delignification was initially employed to recover lignin from the rind, pulp, and whole bagasse fractions of Moroccan sugarcane. The lignin fractions were subsequently modified via silanization and acetylation reactions. The modified lignin and raw lignin were then characterised to assess changes in their physicochemical properties via Fourier transform infrared spectroscopy (FTIR), solubility and thermogravimetric assessment, with both salinization and acetylation modification shown to enhance the solubility properties of the raw lignin of both polar and non-polar solvents. Preliminary investigations into the suitability of employing the modified lignin in hydrogel preparation were also undertaken. The preliminary hydrogels were developed using heating and freeze-thawing methods, while polyvinyl alcohol (PVA) and epichlorohydrin (ECH) were used as the matrix and the crosslinking agents, respectively. Fourier transform infrared spectroscopy (FTIR), rheological analysis, scanning electron microscopy, and thermal analysis were then used to characterize the different lignin-PVA hydrogels. The study showed that the swelling behaviour of the hydrogels was mainly influenced by the nature of the lignin (i.e., modified or raw), and the morphology of the hydrogel surfaces varied depending on the preparation methods. The study showed that the hydrogel based on silanized lignin and PVA had superior mechanical performance and swelling capacity compared to the acetylated lignin-PVA and raw lignin-PVA hydrogels.

An injectable, self-healing, 3D printable, double network co-enzymatically crosslinked hydrogel using marine poly- and oligo-saccharides for wound healing application

In this study, we designed dual network hydrogels with antioxidant and antibacterial activities using marine poly- and oligosaccharides with skin wound healing potential. The synergy between dual enzymatic co-crosslinking based on glucose oxidize (GOx)/horseradish peroxidase (HRP) and electrostatic interaction between positively charged chitooligosaccharides (COS) and phenolated chitosan with negatively charged phenolated alginate formed a hydrogel. The Gel-COS hydrogels exhibited toughness, self-healing, moldability, injectability, and 3D printability. Investigation of the physicochemical properties of the hydrogels exhibited a swelling ratio (< 50%) and in vitro biodegradation after 9 days. Furthermore, the hydrogels exhibited antioxidant properties and antibacterial activity against E. coli and S. aureus. The hydrogels were not cytotoxic and enhanced the migration of 3D cell encapsulated 3T3-L1 fibroblasts, blood vessel formation, as well as in vivo wound healing in a rat model. The Gel-COS hydrogel can be considered a promising skin wound dressing material.

Bioengineering in Salivary Gland Regeneration

Salivary gland (SG) dysfunction impairs the life quality of many patients, such as patients with radiation therapy for head and neck cancer and patients with Sjögren's syndrome. Multiple SG engineering strategies have been considered for SG regeneration, repair, or whole organ replacement. An in-depth understanding of the development and differentiation of epithelial stem and progenitor cells niche during SG branching morphogenesis and signaling pathways involved in cell-cell communication constitute a prerequisite to the development of suitable bioengineering solutions. This review summarizes the essential bioengineering features to be considered to fabricate an engineered functional SG model using various cell types, biomaterials, active agents, and matrix fabrication methods. Furthermore, recent innovative and promising approaches to engineering SG models are described. Finally, this review discusses the different challenges and future perspectives in SG bioengineering.

Temperature Responsive Hydrogel for Cells Encapsulation Based on Graphene Oxide Reinforced poly(N- isopropylacrylamide)/Hydroxyethyl-Chitosan

Temperature-responsive hydrogels exhibit great potentials to encapsulate cells for 3D bioprinting and tissue engineering applications; however, cell aggregation and the hydrogel stiffness determine cell fate and limit its application. Here, we developed a new temperature-responsive hydrogel with interpenetrating polymer networks using poly (N-isopropylacrylamide) (pNiPAM) and hydroxyethyl-chitosan (HECS) with the incorporation of dithiol-modified graphene oxide nanosheets (t-GO). The fabricated hydrogel showed excellent cytocompatibility toward human bone marrow mesenchymal stem cells (hBMSCs), and as expected, the lower critical solution temperature (LCST) could be regulated by changing the weight ratio of pNiPAM/HECS/t-GO. Finally, hBMSCs could be directly encapsulated in the hydrogel at a low temperature (around 20 °C), after then, the cell-laden hydrogel was formed above LCST and displayed high cell viability after 3D culturing. The results indicate that the new pNiPAM/HECS/t-GO hydrogel has the potential to serve as a cell carrier for drug delivery and tissue engineering applications.

Protein by-products: Composition, extraction, and biomedical applications

Significant upsurge in animal by-products such as skin, bones, wool, hides, feathers, and fats has become a global challenge and, if not properly disposed of, can spread contamination and viral diseases. Animal by-products are rich in proteins, which can be used as nutritional, pharmacologically functional ingredients, and biomedical materials. Therefore, recycling these abundant and renewable by-products and extracting high value-added components from them is a sustainable approach to reclaim animal by-products while addressing scarce landfill resources. This article appraises the most recent studies conducted in the last five years on animal-derived proteins' separation and biomedical application. The effort encompasses an introduction about the composition, an overview of the extraction and purification methods, and the broad range of biomedical applications of these ensuing proteins.

Effects of ionic liquids and pulsed electric fields on the extraction of antioxidants from green asparagus roots

Asparagus officinalis root (AR) contains valuable bioactive compounds that have beneficial health properties. The aim of this study was to optimize the extraction of polyphenols and flavonoids in green AR using two novel technologies; pulsed electric field (PEF) and ionic liquids (IL). Further, the antioxidant activity of the obtained extracts was determined. The total polyphenol content, total flavonoid content (TFC), and antioxidant activity (2,2-diphenyl-1-picrylhydrazyl, oxygen radical absorbance capacity and Ferric reducing/antioxidant power assays) were determined. The PEF conditions (PEF strength of 1.6 kV/cm, frequency of 200 Hz and pulse width of 20 µs) resulted in a higher extraction yield as compared to conventional solvent extraction, but had lower antioxidant activities. The optimal conditions for IL extraction were by using 0.5% 1-butyl-3-methylimidazolium chloride at a solid: liquid (S:L) ratio of 1:10 for four min. The IL extraction resulted in a total of 122 mg RE/ mL TFC which was 70 to 80 folds more than the TFC obtained by PEF. The IL extracts had higher TFC and antioxidant activity than PEF, but the safety of the ILs need further research.

Anionic exopolysaccharide from Cryptococcus laurentii 70766 as an alternative for alginate for biomedical hydrogels

Alginates are widely used polysaccharides for biomaterials engineering, which functional properties depend on guluronic and mannuronic acid as the building blocks. In this study, enzymatically crosslinked hydrogels based on sodium alginate (Na-Alg) and the exopolysaccharide (EPS) derived from Cryptococcus laurentii 70766 with glucuronic acid residues were synthesized and characterized as a new potential source of polysaccharide for biomaterials engineering. The EPS was extracted (1.05 ± 0.57 g/L) through ethanol precipitation. Then the EPS and Na-Alg were functionalized with tyramine hydrochloride to produce enzymatically crosslinked hydrogels in the presence of horseradish peroxidase (HRP) and H2O2. Major characteristics of the hydrogels such as gelling time, swelling ratio, rheology, cell viability, and biodegradability were studied. The swelling ratio and degradation profile of both hydrogels showed negative values, indicating an increased crosslinking degree and a lower water uptake percentage. The EPS hydrogel showed similar gelation kinetics compared to the Alg hydrogel. The EPS and its hydrogel were found cytocompatible. The results indicate the potential of EPS from C. laurentii 70766 for biomedical engineering due to its biocompatibility and degradability. Further studies are needed to confirm this EPS as an alternative for Alg in tissue engineering applications, particularly in the development of wound dressing products.

Towards the circular economy — Sustainable fouling mitigation strategies in ultrafiltration of secondary effluent

Membrane separation is an emerging technology for secondary effluent (SE) recycling as an alternative water source. However, SE contains secondary metabolites which form a film on membrane surfaces, leading to a decrease in hydraulic capacity. This is an extensive study of the effect of fouling on UF performance, with a detailed analysis of foulants composition and morphology, and the evaluation of the most effective - either physical or chemical - UF membrane regeneration methods. The paper also investigates FNA (recycled from WWTPs) as an alternative acidic UF membrane cleaning agent. In the UF-DE mode, the most effective backwashing configuration was 1 s every 1 min, where relative membrane permeability decreased by 54% after 4-h, which indicated the presence of physically irreversible fouling after SE separation. An acidic-alkaline cleaning procedure in which the contribution of irreversible fouling was 13% resulted in a 100% efficiency of UF membrane regeneration. The results confirmed that recycled FNA is as efficient as pure reagent-nitric acid V and that the use of FNA can reduce the costs of chemical cleaning by 60%. To fit in with the idea of the circular economy, we proposed a new strategy of reusing spent acidic solutions as an alternative fertiliser.

A Yeast-Derived Peptide Promotes Skin Wound Healing by Stimulating Effects on Fibroblast and Immunomodulatory Activities

Natural Hydrogel-Based Bio-Inks for 3D Bioprinting in Tissue Engineering: A Review

Three-dimensional (3D) printing is well acknowledged to constitute an important technology in tissue engineering, largely due to the increasing global demand for organ replacement and tissue regeneration. In 3D bioprinting, which is a step ahead of 3D biomaterial printing, the ink employed is impregnated with cells, without compromising ink printability. This allows for immediate scaffold cellularization and generation of complex structures. The use of cell-laden inks or bio-inks provides the opportunity for enhanced cell differentiation for organ fabrication and regeneration. Recognizing the importance of such bio-inks, the current study comprehensively explores the state of the art of the utilization of bio-inks based on natural polymers (biopolymers), such as cellulose, agarose, alginate, decellularized matrix, in 3D bioprinting. Discussions regarding progress in bioprinting, techniques and approaches employed in the bioprinting of natural polymers, and limitations and prospects concerning future trends in human-scale tissue and organ fabrication are also presented.

Enhanced keratin extraction from wool waste using a deep eutectic solvent

Abstract: In this study, the solubilization of waste coarse wool as a precursory step for the large-scale valorization of keratin was investigated using a green deep eutectic solvent (DES) based on L-cysteine and lactic acid. The investigation was undertaken via the response surface methodology and based on the Box-Behnken design for four process variables of temperature (70-110 °C), dissolution time (2-10 h), the mass of L-cysteine (0.5-2.5 g) in 20 mL of lactic acid, and wool load in the DES (0.2-0.6 g). Temperature was the most significant process variable influencing keratin yield from the waste coarse wool. The optimum keratin yield (93.77 wt.%) was obtained at the temperature of 105 °C, 8 h dissolution time, with 1.6 g L-cysteine in 20 mL of lactic acid using 0.5 g of wool. This study suggests L-cysteine and lactic acid as a green solvent with the potential to scale up keratin recovery from waste wool without significant destruction in the structure of the recovered keratin. Graphical abstract: [Figure not available: see fulltext.]

Fungal exopolysaccharides: Properties, sources, modifications, and biomedical applications

Fungal exopolysaccharides (EPSs) are natural biopolymers with diverse potential applications in the biomedical, packaging, cosmetic, and food industries. Fungal EPSs are easy to extract and purify polysaccharides that are biodegradable, biocompatible, with low immunogenicity, bioadhesion ability, antibacterial activity, and contain different reactive groups such as hydroxyl, carboxyl, and amine for chemical modifications. Despite fast progress in identifying and characterization fungal EPSs for biomedical applications, i.e., wound healing, drug, and gene delivery, only a few products have been commercialized based on fungal EPSs. This review critically discusses potential biomedical applications of fungi sourced EPSs in tissue engineering (TE), drug and gene delivery.

Production of Fungal Nanochitosan Using High-Pressure Water Jet System for Biomedical Applications

In this present work, fungal nanochitosans, with very interesting particle size distribution of 22 µm, were efficiently generated in high-yield production using a high-pressure water jet system (Star Burst System, Sugino, Japan) after 10 passes of mechanical treatment under high pressure. The specific characterization of fungal chitosan nanofibers suspensions in water revealed a high viscosity of 1450 mPa.s and an estimated transparency of 43.5% after 10 passes of fibrillation mechanical treatment. The mechanical characterization of fungal nanochitosan (NC) film are very interesting for medical applications with a Young's modulus (E), a tensile strength (TS), and elongation at break (e%) estimated at 2950 MPa, 50.5 MPa, and 5.5%, respectively. Furthermore, we exhibited that the fungal nanochitosan (NC) film presented very good long-term antioxidant effect (reached 82.4% after 96 h of contact with DPPH radical solution) and very interesting antimicrobial activity when the nanochitosan (NC) fibers are mainly activated as NC-NH3+ form at the surface of the film with 45% reduction and 75% reduction observed for S. aureus (Gram-positive) and E. coli (Gram-negative), respectively, after 6 h of treatment. These promising antimicrobial and antioxidant activities indicated the high potential of valorization toward biomedical applications.

Sustainable production of low molecular weight phenolic compounds from Belgian Brewers' spent grain

Brewers' spent grain (BSG) is a brewery co-product rich in phenolic compounds which only within Europe, 3-4Mt is generated annually. This study aims to sustainably isolate low-molecular-weight phenolic compounds from Belgian BSG using a microwave-assisted method (MW). Two types of BSG (from light and red malted barley grains) were subjected to MW at 600 and 800 W for 5, 15 and 30 min. MW showed a significant and positive effect on the release of 4-vinylguaiacol, a bioactive compound derived from the thermal decarboxylation of ferulic acid. The amounts of 4-vinylguaiacol in the extracts increased by about 80% after 30 min of MW despite the power applied. In the same time interval, total phenolic contents (TPC) increased of about 70% for light and 60% for red BSG. The highest TPC (13.23 mg/gDM) was obtained at 30 min and 600 W. This sustainable method could help add value to BSG by improving the extractability of bioactive phenolics.

Synergistic complexation of phenol functionalized polymer induced in situ microfiber formation for 3D printing of marine-based hydrogels

The design of 3D printable bio-based hydrogels with enhanced mechanical properties and minimal chemical modification can open new opportunities in the field of biomedical applications. A facile and safe approach is proposed to prepare mechanically reinforced chitosan-based hydrogels via a phenolated polyelectrolyte complex (PHEC) and enzyme-mediated crosslinking. PHEC was formed between phenolated chitosan and alginate, leading to the formation of in situ phenol-functionalized microfibers that exhibited excellent 3D printability. The synergistic complexation enhanced the loss modulus (60 times), toughness, flexibility, and moldability of hydrogel as well as dynamic viscosity (20 times) of the hydrogel precursor compared to individual phenolated chitosan and alginate hydrogels. This complexation endowed the material with excellent printability without sacrificing the hydrogel's elasticity. This study proposes a strategy to design tough and 3D printable marine-based hydrogels based on the synergistic complexation of a phenolated polyelectrolyte complex and enzyme-mediated crosslinking.

Crosslinkers for polysaccharides and proteins: Synthesis conditions, mechanisms, and crosslinking efficiency, a review

Polysaccharides and proteins are important macromolecules for developing hydrogels devoted to biomedical applications. Chemical hydrogels offer chemical, mechanical, and dimensional stability than physical hydrogels due to the chemical bonds among the chains mediated by crosslinkers. There are many crosslinkers to synthesize polysaccharides and proteins based on hydrogels. In this review, we revisited the crosslinking reaction mechanisms between synthetic or natural crosslinkers and polysaccharides or proteins. The selected synthetic crosslinkers were glutaraldehyde, carbodiimide, boric acid, sodium trimetaphosphate, N,N′-methylene bisacrylamide, and polycarboxylic acid, whereas the selected natural crosslinkers included transglutaminase, tyrosinase, horseradish peroxidase, laccase, sortase A, genipin, vanillin, tannic acid, and phytic acid. No less important are the reactions involving click chemistry and the macromolecular crosslinkers for polysaccharides and proteins. Literature examples of polysaccharides or proteins crosslinked by the different strategies were presented along with the corresponding highlights. The general mechanism involved in chemical crosslinking mediated by gamma and UV radiation was discussed, with particular attention to materials commonly used in digital light processing. The evaluation of crosslinking efficiency by gravimetric measurements, rheology, and spectroscopic techniques was presented. Finally, we presented the challenges and opportunities to create safe chemical hydrogels for biomedical applications.

Fabrication and Characterization of Nanocomposite Hydrogel Based on Alginate/Nano-Hydroxyapatite Loaded with Linum usitatissimum Extract as a Bone Tissue Engineering Scaffold

In the current paper, we fabricated, characterized, and applied nanocomposite hydrogel based on alginate (Alg) and nano-hydroxyapatite (nHA) loaded with phenolic purified extracts from the aerial part of Linum usitatissimum (LOH) as the bone tissue engineering scaffold. nHA was synthesized based on the wet chemical technique/precipitation reaction and incorporated into Alg hydrogel as the filler via physical cross-linking. The characterizations (SEM, DLS, and Zeta potential) revealed that the synthesized nHA possess a plate-like shape with nanometric dimensions. The fabricated nanocomposite has a porous architecture with interconnected pores. The average pore size was in the range of 100-200 µm and the porosity range of 80-90%. The LOH release measurement showed that about 90% of the loaded drug was released within 12 h followed by a sustained release over 48 h. The in vitro assessments showed that the nanocomposite possesses significant antioxidant activity promoting bone regeneration. The hemolysis induction measurement showed that the nanocomposites were hemocompatible with negligible hemolysis induction. The cell viability/proliferation confirmed the biocompatibility of the nanocomposites, which induced proliferative effects in a dose-dependent manner. This study revealed the fabricated nanocomposites are bioactive and osteoactive applicable for bone tissue engineering applications.

Injectable hydrogels based on silk fibroin peptide grafted hydroxypropyl chitosan and oxidized microcrystalline cellulose for scarless wound healing

Scars are consequences of the wound healing process, and eliminating scar formation remains a significant challenge. Here, an injectable HMSC hydrogel was developed based on silk fibroin peptide grafted hydroxypropyl chitosan (HPCS-g-SFP) and oxidized microcrystalline cellulose (OMCC) via Schiff base bonds. The synthesized HPCS-g-SFP copolymer displayed efficient free radical scavenging ability on hydrogen hydroxyl radicals and 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH). The pore size, gelling time, equilibrium swelling rate and water retention properties of HMSC hydrogel could be regulated by changing ratio of OMCC and HPCS-g-SFP. Then, tetramethylpyrazine (TMP) was encapsulated into HMSC hydrogel to obtain TMP-loaded HMSC hydrogel. The TMP-loaded HMSC hydrogel facilitated 95% cell activity retention after culturing with human skin fibroblasts (HSF) or human hypertrophic scar fibroblast (HSFB) cells for 24 h. Additionally, in vivo animal experiments confirmed that TMP-loaded HMSC hydrogel promoted rapid wound healing while preventing scar formation. The designed injectable TMP-loaded HMSC hydrogel has potentials in promoting scarless wound healing.

Three-dimensional nanoporous Cu-BTC/graphene oxide nanocomposites with engineered antibacterial properties synthesized via a one-pot solvosonication process

Cu-based nanostructures are a well-known class of antibacterial nanomaterials with broad antibacterial properties. In this study, a facile and one-pot solvosonication process is introduced to synthesize Cu-BTC/graphene oxide nanocomposites with controlled morphological and structural properties. The size range of synthesized Cu-BTC nanoparticles is controlled through the synthesis process by adjusting the content of graphene oxide nanosheets in the synthesis precursor solution. A wide range of sizes and morphologies are achieved via this strategy and the size range of Cu-BTC nanoparticles from 30-40 nm to 15-20 nm are obtained by increasing the content of graphene oxide in the precursor solution from 0.005 to 0.15 mg/ml. We believe an increase in the number of available sites on the basal plane of graphene oxide for the nucleation of Cu-BTC nanocrystals is the main reason for the smaller size range of Cu-BTC nanoparticles with higher concentrations of graphene oxide in the precursor solution. Moreover, the antibacterial activities of the Cu-BTC/graphene oxide nanocomposites are also directly affected by the structure and morphology of Cu-BTC nanoparticles on the basal plane of graphene oxide nanosheets. The synthesized nanocomposite with the smallest size range of Cu-BTC nanoparticles presents the highest antibacterial activity. Consequently, the results presented here suggest that the antibacterial activity of Cu-BTC/graphene oxide nanocomposites can be engineered by controlling the structural and morphological properties of Cu-BTC nanoparticles through the synthesis process.

Exopolysaccharide from the yeast Papiliotrema terrestris PT22AV for skin wound healing

Introduction: Exopolysaccharides (EPSs) are high-value functional biomaterials mainly produced by bacteria and fungi, with nutraceutical, therapeutic and industrial potentials. Objectives: This study sought to characterize and assess the biological properties of the EPS produced by the yeast Papiliotrema terrestris PT22AV. Methods: After extracting the yeast's DNA and its molecular identification, the EPS from P. terrestris PT22AV strain was extracted and its physicochemical properties (structural, morphological, monosaccharide composition and molecular weight) were characterized. The EPS's in vitro biological activities and in vivo wound healing potential were also evaluated. Results: The obtained EPS was water-soluble and revealed an average molecular weight (Mw) of 202 kDa. Mannose and glucose with 97% and 3% molar percentages, respectively, constituted the EPS. In vitro antibacterial activity analysis of the extracted EPS exhibited antibacterial activity (>80%) against Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis at a concentration of 2 mg/mL. The EPS showed cytocompatibility against the human fibroblast and macrophage cell lines and the animal studies showed a dose-dependent wound healing capacity of the EPS with higher wound closure at 10 mg/mL compared to negative and positive control after 14 days. Conclusion: The EPS from P. terrestris PT22AV could serve as a promising source of biocompatible macromolecules with potential for skin wound healing.

Waste Apple Pomace Conversion to Acrylic Acid: Economic and Potential Environmental Impact Assessments

The global demand for acrylic acid (AA) is increasing due to its wide range of applications. Due to this growing demand, alternative AA production strategies must be explored to avoid the exacerbation of prevailing climate and global warming issues since current AA production strategies involve fossil resources. Investigations regarding alternative strategies for AA production therefore constitute an important research interest. The present study assesses waste apple pomace (WAP) as a feedstock for sustainable AA production. To undertake this assessment, process models based on two production pathways were designed, modelled and simulated in ASPEN plus® software. The two competing production pathways investigated included a process incorporating WAP conversion to lactic acid (LA) prior to LA dehydration to generate AA (denoted as the fermentation-dehydration, i.e., FD, pathway) and another process involving WAP conversion to propylene prior to propylene oxidation to generate AA (denoted as the thermochemical-fermentation-oxidation, i.e., TFO, pathway). Economic performance and potential environmental impact of the FD and TFO pathways were assessed using the metrics of minimum selling price (MSP) and potential environmental impacts per h (PEI/h). The study showed that the FD pathway presented an improved economic performance (MSP of AA: USD 1.17 per kg) compared to the economic performance (MSP of AA: USD 1.56 per kg) of the TFO pathway. Crucially, the TFO process was determined to present an improved environmental performance (2.07 kPEI/h) compared to the environmental performance of the FD process (8.72 kPEI/h). These observations suggested that the selection of the preferred AA production pathway or process will require a tradeoff between economic and environmental performance measures via the integration of a multicriteria decision assessment in future work.

Tannic acid: a versatile polyphenol for design of biomedical hydrogels

Tannic acid (TA), a natural polyphenol, is a hydrolysable amphiphilic tannin derivative of gallic acid with several galloyl groups in its structure. Tannic acid interacts with various organic, inorganic, hydrophilic, and hydrophobic materials such as proteins and polysaccharides via hydrogen bonding, electrostatic, coordinative bonding, and hydrophobic interactions. Tannic acid has been studied for various biomedical applications as a natural crosslinker with anti-inflammatory, antibacterial, and anticancer activities. In this review, we focus on TA-based hydrogels for biomaterials engineering to help biomaterials scientists and engineers better realize TA's potential in the design and fabrication of novel hydrogel biomaterials. The interactions of TA with various natural or synthetic compounds are deliberated, discussing parameters that affect TA-material interactions thus providing a fundamental set of criteria for utilizing TA in hydrogels for tissue healing and regeneration. The review also discusses the merits and demerits of using TA in developing hydrogels either through direct incorporation in the hydrogel formulation or indirectly via immersing the final product in a TA solution. In general, TA is a natural bioactive molecule with diverse potential for engineering biomedical hydrogels.

2021

A fast method for in vitro biomineralization of PVA/alginate/biphasic calcium phosphate hydrogel

The development of biomineralized hydrogels with excellent cytocompatibility is of great importance for tissue engineering applications. Here, porous polyvinyl alcohol/alginate/biphasic calcium phosphate (BPS) hydrogels were fabricated via chemical and physical crosslinking methods, and the BPS hydrogels were in vitro biomineralized using urease in saturated calcium-phosphorus solution. For comparison, the BPS hydrogels were also treated using simulated body fluid (SBF) and Dulbecco's modified Eagle's medium with fetal bovine serum (DMEM-FBS), respectively. The physicochemical characterizations confirmed that bone-like apatite was quickly formed on the urease-biomineralized BPS hydrogels compared to the SBF and DMEM-FBS treated hydrogels. Additionally, the bone marrow derived mesenchymal stem cells (BMSCs), adhered and proliferated on the biomineralized hydrogels, were systematically analyzed using cell counting kit-8 (CCK-8). This paper demonstrated the potential urease for fast in vitro biomineralization on hydrogels to improve the cytocompatibility for bone tissue engineering applications.

Anisotropic PLGA microsphere/PVA hydrogel composite with aligned macroporous structures for directed cell adhesion and proliferation

The fabrication of bio tissues using anisotropic constructs capable of repairing and/or replacing diseased bio tissues remains a significant challenge in tissue engineering. Therefore, this study investigated the fabrication of an anisotropic PLGA-microspheres/PVA-hydrogel composite using a novel directional freezing-thawing (DFT) technique. The DFT technique altered the properties of the anisotropic PLGA-microspheres/PVA-hydrogel composite, such that its compressive strength improved from 14.64 ± 1.09 MPa after three DFT cycles to 45.77 ± 6.73 MPa after nine cycles. The utilization of the DFT technique was also shown to enhance the proliferation and adhesion of cultured chondrocyte cells. The obtained results demonstrated that DFT constituted a facile method to fabricate anisotropic microsphere/hydrogel composites with improved and directed cell adhesion characteristics.

Kinetic modelling of the solid-liquid extraction process of polyphenolic compounds from apple pomace: influence of solvent composition and temperature

Abstract This study aims to assess kinetic modelling of the solid-liquid extraction process of total polyphenolic compounds (TPC) from apple pomace (AP). In this regard, we investigated the effects of temperature and solvent (i.e. water, ethanol, and acetone) on TPC extraction over various periods. The highest TPC yield of 11.1 ± 0.49 mg gallic acid equivalent (GAE)/g db (dry basis) was achieved with a mixture of 65% acetone-35% water (v/v) at 60 °C. The kinetics of the solvent-based TPC extraction processes were assessed via first-order and second-order kinetic models, with an associated investigation of the kinetic parameters and rate constants, saturation concentrations, and activation energies. The second-order kinetic model was sufficient to describe the extraction mechanism of TPC from AP. This study provides an understanding of the mass transfer mechanism involved in the polyphenolic compound extraction process, thus facilitating future large-scale design, optimization, and process control to valorize pomace waste. Graphical Abstract

Fruit pomace-lignin as a sustainable biopolymer for biomedical applications

Previous studies have explored the potential of pomace valorization, with an emphasis on the transformation of polysaccharide biopolymers of pomace-cellulose and hemicellulose to produce high-value bioproducts such as microcrystalline cellulose. Notably, opportunities for the exploration of the biopolymer of pomace-lignin for its employment in biomedical applications such as tissue engineering have not been comprehensively explored. There is, therefore, a need for an intervention to highlight the potential of utilizing pomace-lignin as a high-value biomass resource. This review explores potential biomedical applications of pomace-lignin and highlights some of the factors that hinder the industrial utilization of pomace-lignin. In addition, the present review covers lignin chemistry, extraction methods, depolymerization approaches, and prospects of lignin utilization in biomedical applications. It is anticipated that this review will aid future decisions regarding the preferred approaches for the valorization of pomace-lignin.

Iron oxide nanoparticles synthesized via green tea extract for doxorubicin delivery

Background: Due to the limitation of conventional cancer treatment using chemotherapy, the nanoparticle therapeutics have shown enhanced efficacy with alleviating side effects. Objective: The aim of this study was to prepare the superparamagnetic iron oxide nanoparticles (T-C-SPION) for doxorubicin (DOX) loading and delivery. Methods: Here, we reported a simple green strategy to fabricate T-C-SPION using green tea extract and citric acid. Also, the anti-cancer drug, DOX, was used as a model drug to fabricate DOX-loaded nanoparticles. Results: The formed T-C-SPION nanoparticles were spherical with a diameter of 23.8 ± 0.8 nm, as confirmed by Transmission Electron Microscopy (TEM). Besides, Dynamic Light Scattering (DLS) revealed that the prepared nanoparticles were water-dispersible and stable while stored in water for 6 weeks. The CCK-8 assay showed T-C-SPION to have a good cytocompatibility using different iron concentrations (10 ~ 120 ug/mL). Furthermore, T-C-SPION had a higher DOX encapsulation efficiency (Eencaps), around 43.2 ± 1.8 %, which resulted in a lagged release profile of DOX, compared to other types of iron oxide nanoparticles using green tea or citric acid alone. Next, cell viability assay indicated that T-C-SPION with a higher Eencaps showed superior and sustained cytotoxicity compared to the control group. Conclusion: The developed iron oxide nanoparticles synthesized by green tea extract and citric acid in this paper could be considered as a potential drug carrier for cancer therapy applications.

4D printing of patterned multimaterial magnetic hydrogel actuators

This paper demonstrates a new class of printable magnetic hydrogels that can be successfully used for multimaterial direct ink printing (4D printing) of soft actuators. To date, most reports on magnetic actuation have not considered biocompatibility issues associated with magnetic materials and synthetic polymers. For this reason, in this study, considerable attention was given to developing bionanocomposites that exhibit noncytotoxicity and biocompatibility and hence may be used in biomedical applications. Three inks with various concentrations of magnetic nanoparticles (MNPs) were used to print 3D objects, such as tubes (wheels), cubes, and cantilevers. The interactions between MNPs and hydrogel precursor network accounted for excellent shear thinning properties of the inks. Usually, hydrogel actuators move or change a shape upon anisotropic swelling and deswelling, possible only in an aqueous environment. Our study addresses this challenge by incorporating magnetic nanoparticles into the hydrogel, allowing for contactless in-air control of hydrogel motion. Because of the high structural integrity of the hydrogel, we can state that multimaterial direct ink printing is an excellent method for obtaining a 3D construct of high resolution, shape fidelity, tunable distribution of MNPs, and induced macroscopic anisotropy. The magnetic hydrogels are not only highly porous and noncytotoxic towards fibroblasts but also exhibit good mechanical stability and unique magnetic responsiveness. The simple approach allowed us to fabricate different magnetic actuators with various patterns, composed of magnetic and non-magnetic materials. The results demonstrate the interplay between magnetic and nonmagnetic hydrogels that influences the actuation performance of multimaterial objects, as illustrated by magnetically induced rolling, jumping, and bending. It was shown that programmable patterning of the hydrogels leads to the development of macroscopically anisotropic magnetic material. Our study confirmed that the intersection of 4D printing of magnetically responsive hydrogel materials and programmable patterning promises to fulfill future soft robotics' biocompatibility and functionality requirements.

Bioactive peptides from yeast: A comparative review on production methods, bioactivity, structure-function relationship, and stability

Background: Yeast cells are a rich source of protein and have long been investigated for the production of yeast extract as a source of bioactive peptides with different documented bioactivity, e.g. antioxidant, ACE-inhibitory, antidiabetic, as well as prevention of chronic diseases and providing immune responces. Furthermore, yeast cells are known to contribute to generation of bioactive peptides due to their proteolytic activity during fermentation processes, and also release of antimicrobial peptides during growth. Scope and approach: Although reports on preparation and characteristic of yeast extract increased tremendously, research on the functional properties of yeast extract attributed to the content of bioactive peptides and production methods lack a systematic review. Also, the contribution of yeast cells to the production of bioactive peptides during the growth and fermentation process has not been summarized previously. This review summarizes previous studies on yeast-derived peptides, the production methods, the bioactivity, the mechanism of action, as well as the structure-function relationship, and stability of identified peptides. This article would be helpful to promote the application of yeast-derived peptides in research and commercialization. Key finding: Yeast cells and yeast extract have great potentials for producing bioactive peptides with multiple functionalities. Current scientific evidence regarding the potential health benefit of yeast highlights the need for additional investigation on the bioactivity of peptides as influenced by production and purification methods. Also, predicting and designing new peptide sequences with specific functionality with the aid of bioinformatics tools, animal and human studies will effectively transfer these findings into practical and market applications.

A review on biomaterials for ovarian tissue engineering

Considerable challenges in engineering the female reproductive tissue are the follicle's unique architecture, the need to recapitulate the extracellular matrix, and tissue vascularization. Over the years, various strategies have been developed for preserving fertility in women diagnosed with cancer, such as embryo, oocyte, or ovarian tissue cryopreservation. While autotransplantation of cryopreserved ovarian tissue is a viable choice to restore fertility in prepubertal girls and women who need to begin chemo- or radiotherapy soon after the cancer diagnosis, it is not suitable for all patients due to the risk of having malignant cells present in the ovarian fragments in some types of cancer. Advances in tissue engineering such as 3D printing and ovary-on-a-chip technologies have the potential to be a translational strategy for precisely recapitulating normal tissue in terms of physical structure, vascularization, and molecular and cellular spatial distribution. This review first introduces the ovarian tissue structure, describes suitable properties of biomaterials for ovarian tissue engineering, and highlights recent advances in tissue engineering for developing an artificial ovary. Statement of significance: The increase of survival rates in young cancer patients has been accompanied by a rise in infertility/sterility in cancer survivors caused by the gonadotoxic effect of some chemotherapy regimens or radiotherapy. Such side-effect has a negative impact on these patients' quality of life as one of their main concerns is generating biologically related children. To aid female cancer patients, several research groups have been resorting to tissue engineering strategies to develop an artificial ovary. In this review, we discuss the numerous biomaterials cited in the literature that have been tested to encapsulate and in vitro culture or transplant isolated preantral follicles from human and different animal models. We also summarize the recent advances in tissue engineering that can potentially be optimal strategies for developing an artificial ovary.

Ovarian cell encapsulation in an enzymatically crosslinked silk-based hydrogel with tunable mechanical properties

An artificial ovary is a promising approach for preserving fertility in prepubertal girls and women who cannot undergo current cryopreservation strategies. However, this approach is in its infancy, due to the possible challenges of creating a suitable 3D matrix for encapsulating ovarian follicles and stromal cells. To maintain the ovarian stromal cell viability and proliferation, as a first step towards developing an artificial ovary, in this study, a double network hydrogel with a high water swelling capacity (swelling index 15-19) was developed, based on phenol conjugated chi-tosan (Cs-Ph) and silk fibroin (SF) through an enzymatic crosslinking method using horseradish peroxidase. The addition of SF (1%) to Cs (1%) decreased the storage modulus (G') from 3500 Pa (Cs1) to 1600 Pa (Cs-SF1), and the hydrogels with a rapid gelation kinetic produced a spatially ho-mogeneous distribution of ovarian cells that demonstrated 167% proliferation after 7 days. This new Cs-SF hydrogel benefits from the toughness and flexibility of SF, and phenolic chemistry could pro-vide the potential microstructure for encapsulating human ovarian stromal cells.

Hydroxyapatite in oral care products—a review

Calcium phosphate compounds form the inorganic phases of our mineralised tissues such as bone and teeth, playing an important role in hard tissue engineering and regenerative medicine. In dentistry and oral care products, hydroxyapatite (HA) is a stable and biocompatible calcium phosphate with low solubility being used for various applications such as tooth remineralisation, reduction of tooth sensitivity, oral biofilm control, and tooth whitening. Clinical data on these products is limited with varied results; additionally, the effectiveness of these apatite compounds versus fluoride, which has conventionally been used in toothpaste, has not been established. Therefore, this review critically evaluates current research on HA oral care, and discusses the role and mechanism of HA in remineralisation of both enamel and dentine and for suppressing dentine sensitivity. Furthermore, we position HA's role in biofilm management and highlight the role of HA in dental applications by summarising the recent achievement and providing an overview of commercialised HA dental products. The review also indicates the existing limitations and provides direction for future research and commercialisation of apatite-based oral care products.

Optimization of Exopolysaccharide (EPS) Production by Rhodotorula mucilaginosa sp. GUMS16

Exopolysaccharides (EPSs) are important biopolymers with diverse applications such as gelling compounds in food and cosmetic industries and as bio-flocculants in pollution remediation and bioplastics production. This research focuses on enhancing crude EPS production from Rhodotorula mucilaginosa sp. GUMS16 using the central composite design method in which five levels of process variables of sucrose, pH, and ammonium sulfate were investigated with sucrose and ammonium sulfate serving as carbon and nitrogen sources during microbial incubation. The optimal crude EPS production of 13.48 g/100 mL was achieved at 1 g/100 mL of sucrose concentration, 14.73 g/100 mL of ammonium sulfate at pH 5. Variations in ammonium sulfate concentrations (1.27-14.73 g/100 mL) presented the most significant effects on the crude EPS yield, while changes in sucrose concentrations (1-5 g/100 mL) constituted the least important process variable influencing the EPS yield. The Rhodotorula mucilaginosa sp. GUMS16 may have the potential for large-scale production of EPS for food and biomedical applications.

Proliferation and osteogenic differentiation of mesenchymal stem cells on three-dimensional scaffolds made by thermal sintering method

This article presents a thermal sintering method to fabricate porous bone tissue engineering scaffolds based on polycaprolactone (PCL), polylactic acid (PLA), and their composites. The mechanical properties, porous structure, biodegradability, and biocompatibility of sintered scaffolds were evaluated. The scaffolds showed a porosity in the range of 86-91% with a pore size of 75 mμ to 400 mμ. PCL/PLA composite scaffolds showed a Young's modulus of around 49 MPa, which was between the modulus values of PCL (24 MPa) and PLA (63 MPa) scaffolds. Fibroblast cells (SNL) exhibited spreading and adhesion on the scaffolds, and scaffolds demonstrated a significant difference in the osteogenic differentiation of human mesenchymal stem cells (hMSCs) after 7 and 14 days of culture in comparison with the control (tissue culture polystyrene). Our results demonstrated that the thermally sintered PCL/PLA composite scaffold could be a promising candidate for bone tissue regeneration.

Polyphenol rich green tea waste hydrogel for removal of copper and chromium ions from aqueous solution

In this study, green tea waste (GTW) was used to synthesize the iron oxide (IO) nanoparticles (IO@GTW) to facilitate the adsorption of heavy metals from wastewaters. To satisfy structural integrity needs, the synthesized IO@GTW was incorporated into a polyvinyl alcohol (PVA)/alginate polymer network to obtain PVA/alginate/IO (PAI) hydrogels. Experimental techniques of transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR) were subsequently used to confirm the successful synthesis of IO nanoparticles. Scanning electron microscopy (SEM) established the porous microstructure of PAI hydrogels, while FT-IR analysis revealed the physical incorporation of IO@GTW in PAI hydrogels. The adsorption of Cu2+ and Cr6+ on PAI hydrogels was subsequently investigated. The present study was able to show that the removal ratio and adsorption capacity of the synthesized PAI hydrogels depended on the pH, initial concentration of metal ions in the solution, and contact time. The equilibrium isotherms of Cu2+ and Cr6+ adsorption were well-described using Langmuir and Freundlich isotherm models. The adsorption kinetics of Cu2+ can be modelled using the pseudo-second-order model, and the adsorption kinetics of Cr6+ can be modelled using both pseudo-first-order and intraparticle diffusion models. This study, therefore, demonstrates the functionality of integrating green tea waste in a polymeric composite to perform as an effective and green adsorbent for heavy metal removal, thus indicating the viability of its future application in wastewater treatment operations.

3D Printing of Thermoresponsive Hydrogel Laden with an Antimicrobial Agent towards Wound Healing Applications

Thermoresponsive hydrogel-based wound dressings with an incorporated antimicrobial agent can be fabricated employing 3D printing technology. A novel printable ink containing poly(N-isopropylacrylamide) (PNIPAAm) precursors, sodium alginate (ALG), methylcellulose (MC) that is laden with a mixture of octenidine dihydrochloride and 2-phenoxyethanol (Octenisept®, OCT) possess accurate printability and shape fidelity. This study also provides the protocol of ink's use for the 3D printing of hydrogel scaffolds. The hydrogel's physicochemical properties and drug release profiles from the hydrogel specimens to the external solution have been determined at two temperatures (20 and 37 °C). The release test showed a sustained OCT delivery into ultrapure water and the PBS solution. The temperature-responsive hydrogel exhibited antimicrobial activity against Staphylococcus aureus, Candida albicans, and Pseudomonas aeruginosa and demonstrated non-cytotoxicity towards fibroblasts. The thermoresponsive behavior along with biocompatibility, antimicrobial activity, and controlled drug release make this hydrogel a promising class of materials for wound dressing applications.

Methylation Landscape: Targeting Writer or Eraser to Discover Anti-Cancer Drug

Valorization of Waste Apple Pomace for Production of Platform Biochemicals: A Multi-Objective Optimization Study

In line with the prevailing global interest in value extraction from biomass waste streams, the current study explored the technical feasibility of valorizing waste apple pomace (WAP) to produce high-value biochemicals of 5-hydroxymethylfurfural (HMF), lactic acid, and xylitol. Technical feasibility was demonstrated via a process simulation study that employed experimental data and incorporated previously reported approaches in the literature. Economic and environmental performances of the WAP based biorefinery were assessed using the internal rate of return (IRR) and the mass of greenhouse gas emission per unit mass of feedstock (GF) as sufficient performance indicators, respectively. The study was able to show that as the IRR value increased (better economic performance), the GF increased (poorer environmental performance). This suggested that the determination of the optimal condition of the environmental and economic performances would require the imposition of trade-offs. The preferred trade-off condition for enhanced economic and environmental performances was subsequently determined via multi-objective optimization, with a Pareto front containing non-dominated equally optimal solutions subsequently developed. The present work, therefore, provides an in-depth performance analysis of WAP based biorefinery as a waste management strategy. Notably, the proposed strategy of multiple product generation from biomass may be extended to other organic waste based biorefineries. Graphic Abstract: [Figure not available: see fulltext.]

Imaging Constructs: The Rise of Iron Oxide Nanoparticles

Over the last decade, an important challenge in nanomedicine imaging has been the work to design multifunctional agents that can be detected by single and/or multimodal techniques. Among the broad spectrum of nanoscale materials being investigated for imaging use, iron oxide nanoparticles have gained significant attention due to their intrinsic magnetic properties, low toxicity, large magnetic moments, superparamagnetic behaviour and large surface area—the latter being a particular advantage in its conjunction with specific moieties, dye molecules, and imaging probes. Tracers-based nanoparticles are promising candidates, since they combine synergistic advantages for non-invasive, highly sensitive, high-resolution, and quantitative imaging on different modalities. This study represents an overview of current advancements in magnetic materials with clinical potential that will hopefully provide an effective system for diagnosis in the near future. Further exploration is still needed to reveal their potential as promising candidates from simple functionalization of metal oxide nanomaterials up to medical imaging.

Alginate modification via click chemistry for biomedical applications

Alginate biopolymers are characterized by favorable properties, of biocompatibility, degradability, and non-toxicity. However, the poor stability properties of alginate have limited its suitability for diverse applications. Recently, click chemistry has generated significant research interest due to its high reaction efficiency, high selectivity for a single product, harmless byproducts, and processing simplicity. Alginate modified using click chemistry enables the production of alginate derivatives with enhanced physical and chemical properties. Herein, we review the employment of click chemistry in the development of alginate-based materials or systems. Various click chemistries were highlighted, including azide and alkyne cycloaddition (e.g. Copper-(I)-catalyzed azide-alkyne cycloaddition (CuAAC), Strain-promoted alkyne-azide cycloaddition (SPAAC)), Diels-Alder reaction (Inverse electron demand Diels-Alder (IEDDA) cycloaddition, Tetrazine-norbornene Diels-Alder reactions), Thiol-ene/yne addition (Free-radical thiol-ene addition click reactions, Thiol-Michael addition click reactions, Thiol-yne addition click reaction), Oxime based click reactions, and other click reactions. Alginate functionalized with click chemistry and its properties were also discussed. The present study shows that click chemistry may be employed in modifying the mechanical strength, biochemical/biological properties of alginate-based materials. Finally, the applications of alginate-based materials in wound dressing, drug delivery, protein delivery, tissue regeneration, and 3D bioprinting were described and the future perspectives of alginates modified with click chemistry, are subsequently presented. This review provides new insights for readers to design structures and expand applications of alginate using click chemistry reactions in a detailed and more rational manner.

Cover Image, Volume 138, Issue 19

Bone Grafts and Substitutes in Dentistry: A Review of Current Trends and Developments

After tooth loss, bone resorption is irreversible, leaving the area without adequate bone volume for successful implant treatment. Bone grafting is the only solution to reverse dental bone loss and is a well-accepted procedure required in one in every four dental implants. Research and development in materials, design and fabrication technologies have expanded over the years to achieve successful and long-lasting dental implants for tooth substitution. This review will critically present the various dental bone graft and substitute materials that have been used to achieve a successful dental implant. The article also reviews the properties of dental bone grafts and various dental bone substitutes that have been studied or are currently available commercially. The various classifications of bone grafts and substitutes, including natural and synthetic materials, are critically presented, and available commercial products in each category are discussed. Different bone substitute materials, including metals, ceramics, polymers, or their combinations, and their chemical, physical, and biocompatibility properties are explored. Limitations of the available materials are presented, and areas which require further research and development are highlighted. Tissue engineering hybrid constructions with enhanced bone regeneration ability, such as cell-based or growth factor-based bone substitutes, are discussed as an emerging area of development.

Development of marine oligosaccharides for potential wound healing biomaterials engineering

This study aims to investigate the oxidative degradation of chitosan to produce chitooligosaccharides (CHOS) as a potential bioagent for biomaterials engineering. CHOS was produced via microwaved-assisted oxidative degradation of chitosan by using hydrogen peroxide in an acidic aqueous solution. The effects of the H2O2 concentration, reaction time, microwave power, and reaction temperature on the degradation of chitosan were investigated. Following optimization of these parameters, three soluble CHOS fractions CHOS 1 (4-8 kDa), CHOS 2 (3-5 kDa), and CHOS 3 (1-3 kDa) were synthesized and the physicochemical, structural, thermal properties and water solubility were investigated. No significant structure alteration of the initial chitosan was detected by Fourier transform infrared spectroscopy (FTIR), UV-vis, and nuclear magnetic resonance (NMR) analyses, making our microwave-assisted oxidative degradation a valuable method for the production of CHOS. Interestingly, CHOS fractions exhibited improved radical scavenging activities and antibacterial activities compared to the initial chitosan. The half maximal effective concentration (EC50) of the CHOS fractions were found to be in the range of 2.69-0.724 mg/mL significantly lower than the chitosan (7.75, mg/mL). Besides, the CHOS fractions exhibited lower minimum inhibitory concentration (MIC; in the range of 62.5-500 µg/mL) compared to the initial chitosan (>1000 µg/mL). Moreover, the 3T3-Ll fibroblast cells treated with CHOS fractions exhibited more than 95% viability after 48 h of culture. Cell migration and collagen production assays also showed the positive effect of CHOS fractions, particularly CHOS 3. These results indicate that CHOS can be a promising bioactive agent in biomedical applications, in particular for wound healing applications.

Protein-Based 3D Biofabrication of Biomaterials

Protein/peptide-based hydrogel biomaterial inks with the ability to incorporate various cells and mimic the extracellular matrix's function are promising candidates for 3D printing and biomaterials engineering. This is because proteins contain multiple functional groups as reactive sites for enzymatic, chemical modification or physical gelation or cross-linking, which is essential for the filament formation and printing processes in general. The primary mechanism in the protein gelation process is the unfolding of its native structure and its aggregation into a gel network. This network is then stabilized through both noncovalent and covalent cross-link. Diverse proteins and polypeptides can be obtained from humans, animals, or plants or can be synthetically engineered. In this review, we describe the major proteins that have been used for 3D printing, highlight their physicochemical properties in relation to 3D printing and their various tissue engineering application are discussed.

Osteogenesis enhancement using poly (l-lactide-co-d, l-lactide)/poly (vinyl alcohol) nanofibrous scaffolds reinforced by phospho-calcified cellulose nanowhiskers

Electrospun poly (L-lactide-co-D, L-lactide) (PLDLLA)/poly (vinyl alcohol) (PVA) nanofibers were reinforced by various contents (0-1 wt%) of phospho-calcified cellulose nanowhiskers (PCCNWs) as scaffolds in bone applications. The hydrophilicity and rate of hydrolytic degradation of PLDLLA were improved by introducing 10 wt% of PVA. PCCNWs with inherent hydrophilic properties, high aspect ratio, and large elastic modulus enhanced the hydrophilicity, accelerated the rate of degradation, and improved the mechanical properties of the nanofibrous samples. Moreover, calcium phosphate and phosphate functional groups on the surface of PCCNWs possessing act as stimulating agents for cellular activities such as proliferation and differentiation. Besides the physico-chemical properties investigation of PLDLLA/PVA-PCCNWs nanofibrous samples, their cytotoxicity was also studied and they did not show any adverse side effect. Incorporation of PCCNWs (1 wt%) into the PLDLLA/PVA nanofibrous samples showed more enzymatic activities and deposited calcium. The micrograph images of the morphology of human mesenchymal stem cells (hMSCs) cultured on the nanofibrous sample containing 1 wt% of PCCNWs after 14 days of cell differentiation revealed their high potential for bone tissue engineering.

Three-Dimensional Printing of Hydroxyapatite Composites for Biomedical Application

Hydroxyapatite (HA) and HA-based nanocomposites have been recognized as ideal biomaterials in hard tissue engineering because of their compositional similarity to bioapatite. However, the traditional HA-based nanocomposites fabrication techniques still limit the utilization of HA in bone, cartilage, dental, applications, and other fields. In recent years, three-dimensional (3D) printing has been shown to provide a fast, precise, controllable, and scalable fabrication approach for the synthesis of HA-based scaffolds. This review therefore explores available 3D printing technologies for the preparation of porous HA-based nanocomposites. In the present review, different 3D printed HA-based scaffolds composited with natural polymers and/or synthetic polymers are discussed. Furthermore, the desired properties of HA-based composites via 3D printing such as porosity, mechanical properties, biodegradability, and antibacterial properties are extensively explored. Lastly, the applications and the next generation of HA-based nanocomposites for tissue engineering are discussed.

An assessment of the utilization of waste apple slurry in bio-succinic acid and bioenergy production

Recognizing the importance of succinic acid as one of the most relevant platform molecules, the present study assesses the production of succinic acid from waste apple slurry/pomace as a sustainable and renewable feedstock. The assessment has been undertaken by incorporating technical and economic considerations in the analysis while also comparing two succinic acid production scenarios. The aforementioned considerations have been applied by utilizing process simulation results, generated from Aspen Plus software, as input data to undertake economic assessments using classic economic correlations. Employing well-defined system boundaries, scenarios to produce bio-succinic acid with either bioelectricity (scenario 1) or biogas (scenario 2) as co-products were therefore comparatively accessed. This study was able to demonstrate that waste pomace as a feedstock has the potential to generate low-cost succinic acid, while scenario 2 constituted the preferred pathway overall. This study results may provide valuable information to policy makers, to enable better decisions regarding the viability, design and execution of large-scale bio-succinic acid production projects based on waste apple pomace as the preferred feedstock.

A sustainable solvent based on lactic acid andl-cysteine for the regeneration of keratin from waste wool

Keratin dissolution is the first step toward reusing protein-rich biomass such as waste wool, hair, and feather. This paper reports an efficient and environmentally friendly method for the complete recycling of waste wool using a mixture of lactic acid andl-cysteine as a new green deep eutectic solvent (DES) for isolation of keratin. The dissolution time for a 90% dissolubility was 3.5 hours at 95 °C where 22 mg of wool was dissolved per 1 g of the DES. Keratin was obtained after dialysis of the DES mixture followed by lyophilization. In comparison with the raw wool, the α-helix content of keratin decreased while its β content increased. The keratin isolation with the proposed DES only requires water,l-cysteine, and lactic acid and does not require conventional chemicals such as urea, sodium sulfite, and sodium hydroxide.

Advances in Growth Factor Delivery for Bone Tissue Engineering

Shortcomings related to the treatment of bone diseases and consequent tissue regeneration such as transplants have been addressed to some extent by tissue engineering and regenerative medicine. Tissue engineering has promoted structures that can simulate the extracellular matrix and are capable of guiding natural bone repair using signaling molecules to promote osteoinduction and angiogenesis essential in the formation of new bone tissues. Although recent studies on developing novel growth factor delivery systems for bone repair have attracted great attention, taking into account the complexity of the extracellular matrix, scaffolding and growth factors should not be explored independently. Consequently, systems that combine both concepts have great potential to promote the effectiveness of bone regeneration methods. In this review, recent developments in bone regeneration that simultaneously consider scaffolding and growth factors are covered in detail. The main emphasis in this overview is on delivery strategies that employ polymer-based scaffolds for spatiotemporal-controlled delivery of both single and multiple growth factors in bone-regeneration approaches. From clinical applications to creating alternative structural materials, bone tissue engineering has been advancing constantly, and it is relevant to regularly update related topics.

Vaginal Administration of Contraceptives

While contraceptive drugs have enabled many people to decide when they want to have a baby, more than 100 million unintended pregnancies each year in the world may indicate the contraceptive requirement of many people has not been well addressed yet. The vagina is a well-established and practical route for the delivery of various pharmacological molecules, including contraceptives. This review aims to present an overview of different contraceptive methods focusing on the vaginal route of delivery for contraceptives, including current developments, discussing the potentials and limitations of the modern methods, designs, and how well each method performs for delivering the contraceptives and preventing pregnancy.

2020

3D Bioprinting of Lignocellulosic Biomaterials

The interest in bioprinting of sustainable biomaterials is rapidly growing, and lignocellulosic biomaterials have a unique role in this development. Lignocellulosic materials are biocompatible and possess tunable mechanical properties, and therefore promising for use in the field of 3D-printed biomaterials. This review aims to spotlight the recent progress on the application of different lignocellulosic materials (cellulose, hemicellulose, and lignin) from various sources (wood, bacteria, and fungi) in different forms (including nanocrystals and nanofibers in 3D bioprinting). Their crystallinity, leading to water insolubility and the presence of suspended nanostructures, makes these polymers stand out among hydrogel-forming biomaterials. These unique structures give rise to favorable properties such as high ink viscosity and strength and toughness of the final hydrogel, even when used at low concentrations. In this review, the application of lignocellulosic polymers with other components in inks is reported for 3D bioprinting and identified supercritical CO2 as a potential sterilization method for 3D-printed cellulosic materials. This review also focuses on the areas of potential development by highlighting the opportunities and unmet challenges such as the need for standardization of the production, biocompatibility, and biodegradability of the cellulosic materials that underscore the direction of future research into the 3D biofabrication of cellulose-based biomaterials.

Injectable cell-laden poly(N-isopropylacrylamide)/chitosan hydrogel reinforced via graphene oxide and incorporated with dual-growth factors

Injectable hydrogels have gained lots of attention as cell and growth factor carrier in tissue engineering. Here, we developed a novel graphene oxide (GO) reinforced poly(N-isoproplylacrylamide)/chitosan temperature-responsive (pNCG) hydrogel, and the gelation temperature was around 36.4 °C. Then, vascular endothelial cells (VECs) laden pNCG hydrogel was fabricated by encapsulating VECs through the sol-gel transfer process. Also, a sequential release system of monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF) was delicately designed and incorporated into VECs-laden pNCG hydrogel. In vitro and in vivo experiments confirmed that the VECs could proliferate into hydrogel, as well as feasible in-growing angiogenesis. Thus, the injectable pNCG hydrogel holds great potential for biomedical applications.

Poly(acrylic acid) capped iron oxide nanoparticles via ligand exchange with antibacterial properties for biofilm applications

Biofilm infections pose a rising threat to public health due to its existing protective shield, which preventing biocide penetration. Here, the oleate-capped iron oxide nanoparticles (OIONPs) were synthesized by the high-temperature method first; after then, the poly(acrylic acid)-capped iron oxide nanoparticles (PIONPs) were obtained via a ligand exchange reaction between OIONPs and sodium poly(acrylic acid). The physicochemical properties of PIONPs were evaluated by Fourier-transform Infrared Spectroscopy (FT-IR), X-ray Diffraction (XRD), Scanning Transmission Electron Microscopy (STEM), Dynamic Light Scattering (DLS), and zeta potential. The FT-IR analysis confirmed the successful ligand exchange on the surface of iron oxide nanoparticles. STEM images displayed that the prepared PIONPs were monodisperse spherical nanoparticles. The PIONPs were stable in ultrapure water and could be kept for 5 weeks without aggregation. Next, Cell Counting Kit-8 (CCK-8) assay and fluorescent images confirmed the excellent cytocompatibility of PIONPs, while the iron concentration of PIONPs was in the range of 5∼120 mg/L. Finally, PIONPs exhibited efficient antibacterial activity against E. coli and S. aureus, and Staphylococcus aureus subsp. aureus Rosenbach (SASAR) biofilm could be destroyed by treating PIONPs under alternating current (AC) applied field conditions.

Fish collagen: Extraction, characterization, and applications for biomaterials engineering

The utilization of marine-based collagen is growing fast due to its unique properties in comparison with mammalian-based collagen such as no risk of transmitting diseases, a lack of religious constraints, a cost-effective process, low molecular weight, biocompatibility, and its easy absorption by the human body. This article presents an overview of the recent studies from 2014 to 2020 conducted on collagen extraction from marine-based materials, in particular fish by-products. The fish collagen structure, extraction methods, characterization, and biomedical applications are presented. More specifically, acetic acid and deep eutectic solvent (DES) extraction methods for marine collagen isolation are described and compared. In addition, the effect of the extraction parameters (temperature, acid concentration, extraction time, solid-to-liquid ratio) on the yield of collagen is investigated. Moreover, biomaterials engineering and therapeutic applications of marine collagen have been summarized.

Isolation and physicochemical properties of chitin polymer from insect farm side stream as a new source of renewable biopolymer

This study aims to valorize chitin polymer from the side stream of an insect farm and to determine the chitin content, and its physicochemical properties obtained from different processing steps in the insect farm (Adult Black Soldier Fly insect, Puparia, and Flake). We used an acid-base method (using 1 M HCl and 1 M NaOH) as a conventional technique and the acid detergent fiber (ADF) with acid detergent lignin (ADL) methods. The chitin samples are then characterized for thermal stability (TGA-DTA), crystallinity (XRD), chemical compounds (FTIR), and C/N content, and the results were compared to the commercial shrimp chitin. The Puparia had the highest chitin content of 21-33%, followed by the Flake 20-28% and the Adult insect with 7-13% chitin, depending on the extraction method. The chitin yield from ADF-ADL method was on par with the conventional method, while the ADF results were approximately 3-10% higher than the ADF-ADL results. The insect farm side stream is an abundant rich source of high-quality chitin with physiochemical properties comparable with the commercially available shrimp derived chitin.

Silk fibroin nanoscaffolds for neural tissue engineering

The nervous system is a crucial component of the body and damages to this system, either by injury or disease, can result in serious or potentially lethal consequences. An important problem in neural engineering is how we can stimulate the regeneration of damaged nervous tissue given its complex physiology and limited regenerative capacity. To regenerate damaged nervous tissue, this study electrospun three-dimensional nanoscaffolds (3DNSs) from a biomaterial blend of silk fibroin (SF), polyethylene glycol (PEG), and polyvinyl alcohol (PVA). The 3DNSs were characterised to ascertain their potential suitability for direct implant into the CNS. The biological activity of 3DNSs was investigated in vitro using PC12 cells and their effects on reactive astrogliosis were assessed in vivo using a photothrombotic model of ischaemic stroke in mice. Results showed that the concentration of SF directly affected the mechanical characteristics and internal structure of the 3DNSs, with formulations presenting as either a gel-like structure (SF ≥ 50%) or a nanofibrous structure (SF ≤ 40%). In vitro assessment revealed increased cell viability in the presence of the 3DNSs and in vivo assessment resulted in a significant decrease in glial fibrillary acidic protein (GFAP) expression in the peri-infarct region (p < 0.001 for F2 and p < 0.05 for F4) after stroke, suggesting that 3DNSs could be suppressing reactive astrogliosis. The findings enhanced our understanding of physiochemical interactions between SF, PEG, and PVA, and elucidated the potential of 3DNSs as a potential therapeutic approach to stroke recovery, especially if these are used in conjunction with drug or cell treatment. [Figure not available: see fulltext.]

Chitooligosaccharides for wound healing biomaterials engineering

Hydroxyethyl Chitosan-Reinforced Polyvinyl Alcohol/Biphasic Calcium Phosphate Hydrogels for Bone Regeneration

Fabrication of reinforced scaffolds for bone regeneration remains a significant challenge. The weak mechanical properties of the chitosan (CS)-based composite scaffold hindered its further application in clinic. Here, to obtain hydroxyethyl CS (HECS), some hydrogen bonds of CS were replaced by hydroxyethyl groups. Then, HECS-reinforced polyvinyl alcohol (PVA)/biphasic calcium phosphate (BCP) nanoparticle hydrogel was fabricated via cycled freeze-thawing followed by an in vitro biomineralization treatment using a cell culture medium. The synthesized hydrogel had an interconnected porous structure with a uniform pore distribution. Compared to the CS/PVA/BCP hydrogel, the HECS/PVA/BCP hydrogels showed a thicker pore wall and had a compressive strength of up to 5-7 MPa. The biomineralized hydrogel possessed a better compressive strength and cytocompatibility compared to the untreated hydrogel, confirmed by CCK-8 analysis and fluorescence images. The modification of CS with hydroxyethyl groups and in vitro biomineralization were sufficient to improve the mechanical properties of the scaffold, and the HECS-reinforced PVA/BCP hydrogel was promising for bone tissue engineering applications.

Silver‐doped biphasic calcium phosphate/alginate microclusters with antibacterial property and controlled doxorubicin delivery

Biphasic calcium phosphate (BCP) based materials possessed with both excellent biocompatibility and antibacterial activity show potential advantages for biomedical applications. Here, the silver-doped BCP/Alginate (AgBA) microclusters were first fabricated using the double-emulsions method. First, BCP nanoparticles were incorporated into the alginate network to form BCP/Alginate microclusters via the emulsion process. Then, silver nanoparticles (AgNPs) were in situ involved in BCP/Alginate networks to obtain the final AgBA microclusters. Transmission electron microscopy and scanning electron microscopy confirmed that BCP nanoparticles and AgNPs were uniformly distributed in AgBA microclusters. The morphology of AgBA microclusters could be regulated by adjusting emulsion power, and microclusters using the medium powder (500 W) showed a regular spherical shape. Furthermore, CCK-8 analysis identified that AgBA microclusters were cytocompatible culturing with human bone marrow-derived mesenchymal stem cells. Qualitative antibacterial tests exhibited the excellent inhibition effects of AgBA microclusters against Staphylococcus aureus (Gram-positive) and Escherichia coli. (Gram-negative). Lastly, the doxorubicin (DOX)-loaded AgBA microclusters presented adjustable loading efficiency of DOX and controllable release profiles. The cumulative release could reach 73.3% after 72 h in PBS. The above results raised a new route for antibacterial microclusters development for biomedical applications.

Microfluidic-Assisted Preparation of 5-Fluorouracil-Loaded PLGA Nanoparticles as a Potential System for Colorectal Cancer Therapy

This work aims at fabricating 5-fluorouracil (5-FU)-loaded poly (lactic-co-glycolic) acid nanoparticles (PLGA NPs) using a microfluidic (MF) technique, with potential for use in colorectal cancer therapy. In order to achieve 5-FU-loaded NPs with an average diameter of approximately 119 nm, the parameters of MF process with fork-shaped patterns were adjusted as follows: the ratio of polymer to drug solutions flow rates was equal to 10 and the solution concentrations of PLGA as carrier, 5-FU as anti-cancer drug and poly (vinyl alcohol) (PVA) as surfactant were 0.2 (% w/v), 0.01 (% w/v) and 0.15 (% w/v), respectively. In this way, a drug encapsulation efficiency of approximately 95% into the PLGA NPs was obtained, due to the formation of a hydrodynamic flow focusing phenomenon through the MF chip. A performance evaluation of the NP samples in terms of the drug release, cytotoxicity and cell death was carried out. Finally, by analyzing the results after induction of cell death and 4′, 6-diamidino-2-phenylin-dole (DAPI) staining, MF-fabricated NPs containing 5-FU [0.2 (% w/v) of PLGA] revealed the dead cell amounts of 10 and 1.5-fold higher than the control sample for Caco2 and SW-480, respectively.

Polyvinyl Alcohol/Sodium Alginate Hydrogels Incorporated with Silver Nanoclusters via Green Tea Extract for Antibacterial Applications

Silver-based nanoparticles and biomaterials have extensive biomedical applications owing to their unique antimicrobial properties. Thus, green and facile synthesis of such materials is highly desirable. This study reports an antibacterial hydrogel based on polyvinyl alcohol/sodium alginate network with the incorporation of silver nanoparticles (AgNPs), which is greenly synthesized by reductive metabolites obtained from the leaves of green tea. The ‘flower-shape' AgNPs were acquired, it formed a mono-disperse system with a distinct uniform interparticle separation. The average size of AgNPs varied from 129.5 to 243.6 nm, which could be regulated by using different volumes of the green tea extract. Zeta potentials of the AgNPs were from −39.3 mV to −20.3 mV, indicating the moderate stability of the particles in water. In the next stage, the antibacterial polyvinyl alcohol/sodium alginate hydrogels were fabricated by incorporating prepared AgNPs. Scanning Electron Microscopy (SEM) images showed that the porous structure was obtained, and Energy Dispersive X-Ray (EDX) analysis confirmed that the AgNPs were uniformly dispersed in the polymer network. The hydrogels exhibited superior water absorption properties, which were characterized by a high swelling ratio (500-900%) and fast equilibrium. The hydrogels also exhibited good antimicrobial activity in assays with Gram-positive bacteria Escherichia coli and Gram-negative bacteria Staphylococcus aureus. To sum up, a process for the green preparation of antibacterial hydrogels based on AgNPs derived from tea leaves as a conveniently available cheap local agricultural product was established.

2019

The role of microbiota in tissue repair and regeneration

A comprehensive understanding of the human body endogenous microbiota is essential for acquiring an insight into the involvement of microbiota in tissue healing and regeneration process in order to enable development of biomaterials with a better integration with human body environment. Biomaterials used for biomedical applications are normally germ-free, and the human body as the host of the biomaterials is not germ-free. The complexity and role of the body microbiota in tissue healing/regeneration have been underestimated historically. Traditionally, studies aiming at the development of novel biomaterials had focused on the effects of environment within the target tissue, neglecting the signals generated from the microbiota and their impact on tissue regeneration. The significance of the human body microbiota in relation to metabolism, immune system, and consequently tissue regeneration has been recently realised and is a growing research field. This review summarises recent findings on the role of microbiota and mechanisms involved in tissue healing and regeneration, in particular skin, liver, bone, and nervous system regrowth and regeneration highlighting the potential new roles of microbiota for development of a new generation of biomaterials.

Biofabrication of Bacterial Constructs: New Three-Dimensional Biomaterials

An enormous number of bacteria live in almost every environment; from deep oceans to below the surface of the earth or in our gastrointestinal tract. Although biofabrication is growing and maturing very quickly, the involvement of bacteria in this process has not been developed at a similar pace. From the development of a new generation of biomaterials to green bioremediation for the removal of hazardous environmental pollutants or to develop innovative food products in a recent trend, researchers have used cutting-edge biofabrication techniques to reveal the great potential of 3D structured bacterial constructs. These 3D bacterial workhouses may fundamentally change our approach toward biomaterials.

Keratin based thermoplastic biocomposites: a review

Abstract: Fibre reinforced composites have become important materials for manufacturing a diverse range of industrial products. Keratin-rich materials including sheep wool and poultry feathers can have added value by partially substituting synthetic polymers in the production of biocomposites with improved mechanical properties. The strong intermolecular disulfides, hydrogen, ionic and hydrophobic interactions of keratin make it behave as a thermoset material which is not easy to process and thermally blend with other polymers. Therefore, different plasticizers, compatibilizers and coupling agents were investigated in order to make keratin a processable material. This review discusses recent developments in the production of thermoplastic keratin blend biocomposites. In particular, the processing and preparation conditions has been discussed, and their strengths and limitations are enumerated and critically evaluated. Graphical abstract: [Figure not available: see fulltext.].

Plant molecular farming: Production of metallic nanoparticles and therapeutic proteins using green factories

Plants have numerous biological, clinical, pharmaceutical and medicinal purposes for many years; however, their use as a general platform for preparation of desired pharmaceutical and biomedical is relatively current. Secondary metabolites with remarkable and diverse biological functions are produced by medicinal plants. Significant advancements in nanosciences have enabled various applications in the development of new generation of drug molecules. Due to the application of toxic solvents and high energy consumption of conventional physical and chemical approaches, greener and eco-friendly methods are essential and vital. Plants can provide an outstanding alternative for the production of phytomaterials and biomaterials, and this review highlights the exogenous and endogenous syntheses of nanoparticles using living plants. Additionally, the plant nano-molecular farming of proteins including collagen, gelatin, elastin, recombinant anti-cancer monoclonal antibodies and recombinant anti-cancer vaccines, are discussed.

What Do We Know about Diet and Markers of Cardiovascular Health in Children: A Review

Chronic diseases such as cancer, diabetes, and cardiovascular diseases (CVD) are the main health concerns in the 21st century, with CVD as the number one cause of mortality worldwide. Although CVD hard endpoints such as stroke or heart attack do not usually occur in children, evidence shows that the manifestation of CVD risk factors begins in childhood, preceding clinical complications of CVD in adulthood. Dietary intake is a modifiable risk factor that has been shown to make a substantial contribution to the risk of CVD in adulthood. However, less is known about the association between dietary intake and markers of cardiovascular health in children. This review summarises the current evidence on the relationship between dietary intake and markers of cardiovascular health including traditional CVD risk factors, physical fitness, and indices of arterial stiffness and wave reflection in children. Original research published in English, between January 2008 and December 2018 fulfilling the objective of this review were screened and included. Findings show that adaptation of a healthy lifestyle early in life can be beneficial for reducing the risk of CVD later in life. Furthermore, keeping arterial stiffness low from a young age could be a potential CVD prevention strategy. However, limited studies are available on diet-arterial stiffness relationship in children, and future research is required to better understand this association to aid the development and implementation of evidence-based strategies for preventing CVD-related complications later in life.

Shear thinning/self-healing hydrogel based on natural polymers with secondary photocrosslinking for biomedical applications

Injectable hydrogel systems are useful in many biomedical applications, including drug or cell delivery carriers and scaffolds. Here, we describe the design and characterization of a shear thinning hydrogel that undergoes a disassembly when shear forces are applied during injection and is self-healing once the shear forces are removed. This hydrogel is based on a cyclodextrin modified alginate, and a methacrylated gelatin which initially forms through a weak guest-host interaction between hydrophobic cyclodextrin cavities and the aromatic residue of gelatin. Methacrylated gelatin possesses photocrosslinkable functionalities which can go through a light-initiated polymerization to create secondary crosslinking sites and further crosslink the matrix. The shear thinning and self-healing behavior of these gels monitored in low and high strain range, viscosity of the hydrogels components and gelation kinetic were studied. The rheological analyses showed the formation of shear thinning gels which were further stabilized by visible light exposure. The cytotoxicity of the hydrogels towards human mesenchymal stem cells were assessed and the rate of mass loss over a week period was studied. © 2018 Elsevier Ltd

Status and future scope of plant-based green hydrogels in biomedical engineering

Hydrogels are the most iconic class of soft materials, and since their first report in the literature, they have attracted the attention of uncountable researchers. Over the past two decades, hydrogels have become smart and sophisticated materials with numerous applications. This class of soft materials have been playing a significant role in biomedicine due to their tunable and often programmable properties. Hydrogels from renewable polymers have been popularized in biomedical applications as they are often biocompatible, easily accessible, and inexpensive. The challenge however has been to find an ideal plant-based hydrogel for biomedicine that can mimic critical properties of human tissues in terms of structure, function, and performance. In addition, natural polymers can readily be functionalized to engineer their chemical and physical uproperties pertinent to drug delivery and tissue engineering. Here, the most recent advances in the synthesis, fabrication, and applications of plant-based hydrogels in biomedical engineering are reviewed. We cover essential and updated information about plants as green sources of biopolymers for hydrogel synthesis, general aspects of hydrogels and plant-based hydrogels, and thorough discussion regarding the use of such hydrogels in the biomedical engineering area. Furthermore, this review details the present status of the field and answers several important questions about the potential of plant-based hydrogels in advanced biomedical applications including therapeutics, tissue engineering, wound dressing, and diagnostics., etc.

Graft polymerization onto wool fibre for improved functionality

Electrochemical investigation of amino acids Parkia seeds using the composite electrode based on Copper/Carbon nanotube/Nanodiamond

An electrochemical biosensor comprising copper, nano-diamond (ND) and carbon nanotube (CNT) has been fabricated to detect the amino acids of Parkia speciosa (PS) seeds. Parkia speciosa (stink bean), a Southeast Asian legume, is composed of medicinal chemicals which exhibit biological activities. The electro-catalytic activity of three electrodes Cu/CNT/ND, Zn/CNT/ND and NiO/CNT/ND was studied using 5 mM potassium ferrocyanide in 0.1 MKCl. The Zn/CNT/ND electrode exhibited irreversible reaction free oxidation with reduction peaks at -1 V, whereas, a pair redox peaks was observed for Cu/CNT/ND electrode. The immobilization of l-amino acid oxidase on the Cu/CNT/ND electrode was carried out to catalyze the amino acids detection. It was observed that the anodic and cathodic peak currents increased linearly with both the square root of the scan rate (ν1/2) and scan rate (ν) over the studied scan range of 0.01-0.1 V/s with high correlation coefficients and following both the adsorption and the diffusion-controlled mechanisms. The developed biosensor displayed a very good electro-catalytic activity toward the oxidation of the amino acid to release H2O2 and NH3 as a result of the reaction between the active sites and the Parkia speciosa component. This was also confirmed by a drop in the pH value from 6.8 to 6.5 and a change in the color of the solution from green to yellow (releasing H2S). The impedance results indicated an inductance behavior due to the co-formation of the hydrogen peroxide (H2O2) and the water via the adsorption on the electrode surface.

2018

Current and novel polymeric biomaterials for neural tissue engineering.

The nervous system is a crucial component of the body and damages to this system, either by of injury or disease, can result in serious or potentially lethal consequences. Restoring the damaged nervous system is a great challenge due to the complex physiology system and limited regenerative capacity. Polymers, either synthetic or natural in origin, have been extensively evaluated as a solution for restoring functions in damaged neural tissues. Polymers offer a wide range of versatility, in particular regarding shape and mechanical characteristics, and their biocompatibility is unmatched by other biomaterials, such as metals and ceramics. Several studies have shown that polymers can be shaped into suitable support structures, including nerve conduits, scaffolds, and electrospun matrices, capable of improving the regeneration of damaged neural tissues. In general, natural polymers offer the advantage of better biocompatibility and bioactivity, while synthetic or non-natural polymers have better mechanical properties and structural stability. Often, combinations of the two allow for the development of polymeric conduits able to mimic the native physiological environment of healthy neural tissues and, consequently, regulate cell behaviour and support the regeneration of injured nervous tissues. Currently, most of neural tissue engineering applications are in pre-clinical study, in particular for use in the central nervous system, however collagen polymer conduits aimed at regeneration of peripheral nerves have already been successfully tested in clinical trials. This review highlights different types of natural and synthetic polymers used in neural tissue engineering and their advantages and disadvantages for neural regeneration.

Leishmania treatment and prevention: Natural and synthesized drugs.

Leishmaniasis affects over 150 million people all over the world, especially in subtropical regions. Currently used antileishmanial synthesized drugs are associated with some drawbacks such as resistance and cytotoxicity, which hamper the chances of treatment. Furthermore, effective leishmanial vaccines are not well developed. Promising chemotherapy, either from natural or synthetic compounds, was or still is the most promising treatment. This review focuses on recent findings in drugs used for the treatment of leishmaniasis including; chemical and natural antileishmanial moieties, different potential targets, as well as various trials of vaccination development. Special emphasis has been paid to the mechanisms of the drugs, their safety and where possible, the structure-activity relationship to enable guided future drug discovery.

In situ-forming and pH-responsive hydrogel based on chitosan for vaginal delivery of therapeutic agents

Nail Properties and Bone Health: A Review.

Physicochemical properties of nail may offer valuable insight into the health of bone. Currently, dual-energy X-ray absorptiometry (DXA) is the gold standard technique for evaluating bone health through bone mineral density (BMD). However, only 70% of fractures are explained by low BMD according to DXA. Therefore, the World Health Organisation recommended the need for the development of alternative methods of assessing bone health. Keratin and collagen type I are major proteins in nail and bone, respectively. Both of these proteins undergo post-translational modifications, with a possible correlation between the degree of post-translational modifications in keratin and collagen. Raman spectroscopy is a technique used to detect changes in protein composition and structure. As changes in protein function and structure may be associated with the development of osteoporosis, Raman spectroscopy may be a valuable adjunct to assess bone health and fracture risk. This review critically evaluates various methods and techniques to identify the link between nail properties and bone health. The strengths and limitations of various studies and the potential use of nail protein and minerals to evaluate bone health have been also presented.

A new adhesive from waste wool protein hydrolysate

This study aimed to produce a new non-toxic adhesive system consisting of wool-hydrolysed (WH) and a commercial wet-strength agent for paper (Kymene® 557H) which is an aqueous solution of cationic polyamidoamine-epichlorohydrin (PAE) resins. The WH mixed with Kymene (WH-K) and used as an adhesive for bonding pine veneer. Rheology aspects of the blends measured in different WH-K weight ratios and the effect of reaction time on the lap-shear strengths of wood composites bonded with WH-K adhesives were evaluated. The physicochemical properties of the newly developed wood adhesive system were characterised using FTIR, DSC and TGA. Wood composites bonded with WH-K adhesive had shear strengths comparable to or higher than those bonded with commercial phenol-formaldehyde resins. Wood composites bonded with the new adhesive system demonstrated high water resistance and retained relatively high strength even after treated with boiling water. The new adhesive system is non-toxic, free from formaldehyde and friendly to use for diverse applications. Thus, we anticipate that this new adhesive system will be potential candidate for bio-composites and packaging applications. © 2018 Elsevier Ltd.

Antioxidant activities and caffeic acid content in New Zealand asparagus (Asparagus officinalis) roots extracts

Asparagus officinalis are perennial plants that require re-planting every 10-20 years. The roots are traditionally mulched in the soil or treated as waste. The A. officinalis roots (AR) contain valuable bioactive compounds that may have some health benefiting properties. The aim of this study was to investigate the total polyphenol and flavonoid contents (TPC and TFC, respectively) and antioxidant (2,2-diphenyl-1-picrylhydrazyl (DPPH), Oxygen Radical Absorbance Capacity (ORAC) and Ferric Reducing/Antioxidant Power (FRAP) assays) activities of New Zealand AR extract. The antioxidant activity decreased with a longer extraction time. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.

Characterization of phenolic compounds in wine lees

The effect of vinification techniques on phenolic compounds and antioxidant activity of wine lees are poorly understood. The present study investigated the antioxidant activity of white and red wine lees generated at early fermentation and during aging. In this study, the total phenol content (TPC), total tannin content (TTC), mean degree of polymerization (mDP), and antioxidant activities of five white and eight red wine lees samples from different vinification backgrounds were determined. The results showed that vinification techniques had a significant (p < 0.05) impact on total phenol and tannin content of the samples. White wine lees had high mDP content compared with red ones. Catechin (50-62%) and epicatechin contents were the predominant terminal units of polymeric proanthocyanidin extracted from examined samples. Epigallocatechin was the predominant extension unit of white wine lees, whereas epicatechin was the predominant compound in red wine marc. The ORAC (oxygen radical absorbance capacity) assay was strongly correlated with the DPPH (α,α-diphenyl-β-picrylhydrazyl) assay, and the results showed the strong antioxidant activities associated with red wine lees (PN > 35 mg Trolox/g FDM) (PN: Pinot noir lees; FDM: Freeze-dried Material). This study indicates that tannin is one of the major phenolic compounds available in wine lees that can be useful in human and animal health applications. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.

Polysuccinimide and its derivatives: Degradable and water soluble polymers (review)

Interest for water soluble polymers which show biocompatibility and degradability is growing due to their potential applications in medical sciences. Polysuccinimide (PSI), commonly synthesized through thermal polymerization, is a polyimide precursor for the production of such biocompatible and degradable polymers namely polyaspartic acid and various polyaspartamides. Polyaspartic acid is usually obtained by hydrolysis of PSI while polyaspartamide is produced by ring opening of PSI using a nucleophilic reagent. The presence of amide linkages in these polymers gives them peptide-like structures which is prone to hydrolysis and subsequent degradation. These derivatives could be potential substitutes for different polyamino acids in many medical applications. This review compiles the works carried out on developing polysuccinimide and its derivatives as well as the main synthetic routs and characterization methods. © 2018 Elsevier Ltd

Flaxseed: Composition, detoxification, utilization, and opportunities

Flaxseed cake is a low value, a protein-rich by-product of flaxseed oil pressing companies. Flaxseed oil has been known as a rich source of omega-3 fatty acids and has been widely used. However, due to the presence of anti-nutritive compounds such as phytic acid, linatine, and cyanogenic glycosides, flaxseed cake that has a high protein content has limited food application. Cyanogenic compounds, particularly cyanogenic glycosides, can be degraded to toxic HCN upon ingestion. Therefore, the cake with a high content of fibre and protein with great nutritional potential has been underutilised and has some limited animal feed applications. Detoxification of the flax cake from cyanogenic content can, therefore, improve the market value of the protein and increase its food application. This review focuses on various available methods for detoxification of flax seed cake with emphasis on nutritional properties of the final product. The impact of various flaxseed cake detoxification methods on the protein is critically evaluated, discussing the options available toward increasing the food application value of this high protein product. © 2017 Elsevier Ltd

Polyphenol uses in biomaterials engineering

Polyphenols are micronutrients obtained from diet that have been suggested to play an important role in health. The health benefits of polyphenols and their protective effects in food systems as antioxidant compounds are well known and have been extensively investigated. However, their functional roles as a “processing cofactor” in tissue engineering applications are less widely known. This review focuses on the functionality of polyphenols and their application in biomaterials. Polyphenols have been used to stabilize collagen and to improve its resistance to degradation in biological systems. Therefore, they have been proposed to improve the performance of biomedical devices used in cardiovascular systems by improving the mechanical properties of grafted heart valves, enhancing microcirculation through the relaxation of the arterial walls and improving the capillary blood flow and pressure resistance. Polyphenols have been found to stimulate bone formation, mineralization, as well as the proliferation, differentiation, and the survival of osteoblasts. These effects are brought about by the stimulatory effect of polyphenols on osteoblast cells and their protective effect against oxidative stress and inflammatory cytokines. In addition, polyphenols inhibit the differentiation of the osteoclast cells. Collectively, these actions lead to promote bone formation and to reduce bone resorption, respectively. Moreover, polyphenols can increase the cross-linking of dentine and hence its mechanical stability. Overall, polyphenols provide interesting properties that will stimulate further research in the bioengineering field. © 2018 Elsevier Ltd

2017

Keratin: dissolution, extraction and biomedical application

Keratinous materials such as wool, feathers and hooves are tough unique biological co-products that usually have high sulfur and protein contents. A high cystine content (7-13%) differentiates keratins from other structural proteins, such as collagen and elastin. Dissolution and extraction of keratin is a difficult process compared to other natural polymers, such as chitosan, starch, collagen, and a large-scale use of keratin depends on employing a relatively fast, cost-effective and time efficient extraction method. Keratin has some inherent ability to facilitate cell adhesion, proliferation, and regeneration of the tissue, therefore keratin biomaterials can provide a biocompatible matrix for regrowth and regeneration of the defective tissue. Additionally, due to its amino acid constituents, keratin can be tailored and finely tuned to meet the exact requirement of degradation, drug release or incorporation of different hydrophobic or hydrophilic tails. This review discusses the various methods available for the dissolution and extraction of keratin with emphasis on their advantages and limitations. The impacts of various methods and chemicals used on the structure and the properties of keratin are discussed with the aim of highlighting options available toward commercial keratin production. This review also reports the properties of various keratin-based biomaterials and critically examines how these materials are influenced by the keratin extraction procedure, discussing the features that make them effective as biomedical applications, as well as some of the mechanisms of action and physiological roles of keratin. Particular attention is given to the practical application of keratin biomaterials, namely addressing the advantages and limitations on the use of keratin films, 3D composite scaffolds and keratin hydrogels for tissue engineering, wound healing, hemostatic and controlled drug release.

Antioxidant and functional properties of protein hydrolysates obtained from squid pen chitosan extraction effluent.

Squid pens were subjected to alkali hydrolysis to extract chitin and chitosan. Proteins present in the alkaline extraction wastewater were recovered at pH 3, 4, 5 and 6, and were subjected to hydrolysis by trypsin, pepsin and a bacterial protease called HT for 1, 2, 4 and 24h. Hydrolysis of the extracted proteins with either trypsin or HT generated more antioxidant activity than hydrolysis with pepsin. Higher ACE-inhibitory activity was generated in the trypsin and pepsin hydrolysates than in the HT hydrolysate. Squid pen protein recovered from chitosan processing waste alkaline solution can be a potential source of bioactive peptides for addition to foods. The antioxidant and ACE-inhibitory activities of the extracted proteins were initially low and increased upon incubation with the proteases. Pepsin generated significantly lower (P<0.05) antioxidant activities compared to trypsin and HT, while trypsin and pepsin hydrolysates exhibited higher ACE-inhibitory activity than HT (P<0.05).

An improved method for solubilisation of wool keratin using peracetic acid

Keratin in wool is a potentially important natural source of protein with many applications. However, solubilisation of keratin from wool is challenging. The yield of solubilised keratin was investigated using peracetic acid (PA) treatment of wool. The yield of keratin obtained by extraction of wool with various concentrations of PA (6, 12, 24 and 36%) with 1, 2, or 3 days of treatment time was examined. Treatment of wool for two days with 24% PA was found to be the optimum treatment condition, resulting in a 57% yield of water soluble keratin (WSK) and a 40% yield of insoluble keratin (ISK). The physicochemical properties of the obtained keratin samples were determined using XRD, FTIR and SDS-PAGE. FTIR analysis of the WSK and ISK showed both extracts had a high content of cysteine-S-sulfonated residues and SDS-PAGE confirmed that the extracts contained proteins in the 40-60 kDa molecular weight range. © 2017 Elsevier Ltd.

Development and characterization of a xenograft material from New Zealand sourced bovine cancellous bone

A xenograft (bovine hydroxyapatite [BHA]) was developed from New Zealand sourced bovine cancellous bone by a successful defatting and deproteinizing procedure. The BHA was chemically, compositionally and structurally characterized. Fourier transform infrared spectroscopy confirmed the removal of organic matter from the bone matrix and the presence of carbonate (CO3 2-), hydroxyl (OH−), and phosphate (PO4 3-) functional groups. X-ray diffraction analysis suggested that the processed bone corresponds characteristically to hydroxyapatite (HA). SEM analysis showed that the BHA has an interconnected porous architecture with a pore diameter ranging from 100 to 700 μm while µCT analysis calculated the total porosity as 73.46% ± 1.08. Furthermore, the BHA was stable up to 1000°C and lost only 1.8% of its weight. The Ca/P molar ratio of the BHA was 1.58, which is comparable with commercially available natural HA-Endobon®. After 28 days of incubation in simulated body fluid (SBF), the pH value only fluctuated between 7.1 and 7.5 and the BHA scaffold did not degrade significantly by weight indicating the scaffold had excellent chemical and structural stability. In vitro studies showed the BHA was cytocompatible and supported the proliferative growth of Saos-2 osteoblast cells. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1054-1062, 2017. © 2016 Wiley Periodicals, Inc.

2016

Bio-scaffolds produced from irradiated squid pen and crab chitosan with hydroxyapatite/β-tricalcium phosphate for bone-tissue engineering.

In this study, bio-scaffolds have been developed using irradiated chitosan from different sources - squid pen (RS) and crab shell (RC) - with hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) at a chitosan/HA/β-TCP ratio of 50/30/20. The bio-scaffolds were prepared at two different freezing temperature (-20°C and -80°C) followed by lyophilisation. To enhance the mechanical properties, the bio-scaffolds were cross-linked using sodium tripolyphosphate (TPP) followed by lyophilisation. The composition and morphology of the bio-scaffolds were characterized using XRD, SEM, TEM and μ-CT. The pore size of the porous scaffolds ranged from 90 to 220μm and the scaffolds had 70-80% porosity. The scaffolds had a water uptake ratio of more than 10, and a controlled biodegradation in the range of 30-40%. These results suggest that the physical and biological properties of chitosan-based bio-scaffolds can be a promising biomaterial for bone-tissue regeneration.

Evaluation of keratin extraction from wool by chemical methods for bio-polymer application

This study investigated some physicochemical properties of keratin extracted from Merino wool using five chemical extraction methods: alkali hydrolysis, sulfitolysis, reduction, oxidation, and extraction using ionic liquid. The ionic liquid method produced the highest protein yield (95%), followed by sulfitolysis method (89%), while the highest extraction yield was obtained with the reduction method (54%). The lowest yield was obtained with the oxidation method (6%). The oxidation extract contained higher molecular weight (>40 kDa) protein components, whereas the alkali hydrolysis extract contained protein material of <10 kDa. The sulfitolysis, reduction, and ionic liquid extracts contained various protein components between 3.5 and 60 kDa. Keratin obtained from various extraction methods had different yield, morphology, and physicochemical properties. None of the samples were toxic to L929 fibroblast cells up to a concentration of 2.5 mg/mL. Apart from the alkali hydrolysis extract, all other keratin extracts (reduction, sulfitolysis, ionic liquid, and oxidation) showed Fourier transform infrared adsorption peaks attributed to the sulfitolysis-oxidation stretching vibrations of cysteine-S-sulfonated residues, with the oxidation extract showing the highest content of cysteine-S-sulfonated residues. This study indicates that the properties of the keratin extract obtained vary depending on the extraction method used, which has implications for use in structural biomaterial applications. © The Author(s) 2016.

Marine shells: Potential opportunities for extraction of functional and health-promoting materials

Marine shell waste is a very rich source of several bioactive compounds and materials, such as calcium, chitin, pigments, and proteins. Currently, this waste material is greatly underutilized and contributes to significant environmental problems due to off-odor and concentration of minerals in landfill. The main objective of this review is to highlight the potential to add value to and maximize the utilization of this waste stream. Therefore, this review provides up-to-date information on various compounds available in marine shells that are generated as waste coproduct from commercial processing operations and their potential uses. Methods are described for extraction of these compounds for use in food and pharmaceutical applications. © 2016 Taylor & Francis Group, LLC.

Injectable gel from squid pen chitosan for bone tissue engineering applications

The aim of this study was to evaluate the potential of squid pen chitosan for developing injectable gels for bone tissue engineering applications. Gel mixtures made of glycerol phosphate mixed with crab (RC) or squid pen (RS) chitosan (2 % w/v) at four different concentrations (0, 30, 50 and 70 %) of calcium phosphate compounds (CaP, hydroxyapatite and β-tricalcium phosphate, HA/β-TCP) were investigated for their biocompatibility and mechanical properties. The proposed gel rapidly settled (<3 min) and formed a stable gel at body temperature (i.e. 37 °C). The chemical compositions and crystallinity of the gels were characterised by FTIR and XRD. The surface morphology and microstructure of the gels were characterised using SEM. The physical properties (such as water uptake, washout resistant and syringeability), compressive modulus and biocompatibility properties (cell cytotoxicity) of the gels were also studied. The RS chitosan gels showed the highest water uptake ability (>2000 %), compressive modulus (up to 26 kPa) and better cell (Saos-2) compatibility compared to the RC chitosan. This study showed that RS chitosan is a promising alternative to commercially available crab/shrimp chitosan for producing injectable gels for tissue engineering applications. Graphical Abstract: [Figure not available: see fulltext.] © 2015, Springer Science+Business Media New York.

Thermochemical Properties of Glass Wool/Maerogel Composites

Aerogel blankets are composites of silica aerogel particles dispersed in a reinforcing fiber matrix that turns the brittle aerogel into durable and flexible insulating materials. In this study, silica aerogel was loaded on glass wool with different concentrations (0-18.6%) and morphological and thermal characteristics of the aerogel blankets were studied. Rate of modified blanket decomposition was slower at temperatures between 250°C and 650°C due to the retardant effect of the silica aerogel. The average diameter of the fiber for either original glass wool or modified glass wool materials was approximately 20 μm and samples had porous, interconnected particles with dendritic-like structure. © 2016 Bahador Dastorian Jamnani et al.

Synthesis of macro and micro porous hydroxyapatite (HA) structure from waste kina (Evechinus chloroticus) shells

The aim of this study was to investigate the conversion of waste kina shells (Evechinus chloroticus) into hydroxyapatite (HA, Ca10(PO4)6(OH)2), while preserving its porous and interconnected structure. The shells were subjected to a pyrolysis process followed by a chemical synthesis step at ambient pressure and at a low temperature of 100°C under alkaline condition. The obtained HA had a porous structure with large pores ranged 300-500μm and small pores of 10-20μm, which is considered beneficial for bone repair materials to ensure blood and nutrient circulation required for bone regeneration. The samples also had high concentrations of magnesium (3.44%) which is an important component of HA used in bone grafting. X-Ray Diffractometer results indicated that a HA layer was formed on the surface of the calcium carbonate structure of the shells. The synthesized HA had no toxicity to the osteoblast cells and the porous and interconnected microstructure of the shells was preserved during an incubation period of 3 days. The obtained HA may have potential applications in bone tissue enegineering. © 2016 Taiwan Institute of Chemical Engineers.

2015

A novel squid pen chitosan/hydroxyapatite/β-tricalcium phosphate composite for bone tissue engineering

Bio-mimetic composite scaffold from mussel shells, squid pen and crab chitosan for bone tissue engineering.

In the present study, chitosan/hydroxyapatite (HA)/β-tircalcium phosphate (β-TCP) composites were produced using squid pen derived chitosan (CHS) and commercial crab derived chitosan (CHC). CHS was prepared from squid pens by alkaline N-deacetylation. HA and β-TCP were extracted from mussel shells using a microwave irradiation method. Two different composites were prepared by incorporating 50% (w/w) HA/(β-TCP) in CHS or CHC followed by lyophilization and cross-linking of composites by tripolyphosphate (TPP). The effect of different freezing temperatures of -20, -80 and -196 °C on the physicochemical characteristics of composites was investigated. A simulated body fluid (SBF) solution was used for preliminary in vitro study for 1, 7, 14 and 28 days and the composites were characterized by XRD, FTIR, TGA, SEM, μ-CT and ICP-MS. Porosity, pore size, water uptake; water retention abilities and in vitro degradations of the prepared composites were evaluated. The CHS composites were found to have higher porosity (62%) compared to the CHC composites (porosity 42%) and better mechanical properties. The results of this study indicated that composites produced at -20 °C had higher mechanical properties and lower degradation rate compared with -80 °C. Chitosan from the squid pen is an excellent biomaterial candidate for bone tissue engineering applications.

Synthesis of nano-hydroxyapatite (nHA) from waste mussel shells using a rapid microwave method

Nano-crystalline hydroxyapatite (HA, Ca10(PO4)6(OH)2) was produced from waste mussel shells using a rapid microwave irradiation method. Mussel shells were converted to rod like nano-crystalline HA particles of 30-70 nm long using 0.1 M EDTA as a chelating agent for 30 min after an appropriate pre-treatment and an irradiation step in a microwave with a power of 1.1 kW. The produced HA was characterised using X-ray diffraction (XRD), scanning electron microscopy (SEM) coupled with energy-dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM), thermo gravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT-IR) and inductively coupled plasma mass spectrometry (ICP-MS) to determine the morphology, particle size, crystal phases, elemental composition and thermal behaviour. Furthermore, to benchmark the synthesized HA obtained from mussel shells, it was compared with a commercially pure HA (Sigma-Aldrich). The thermal analysis showed that the synthesized HA has remarkable heat stability at 1000 °C, and the XRD and FTIR results showed a high purity of the synthesized HA powders. Compared to the conventional hydrothermal treatment, microwave-assisted method has the advantages of an increased rate of HA formation. The obtained HA have potential engineering applications as materials for bone-tissues. © 2014 Elsevier B.V. All rights reserved.

Development and characterization of hydroxyapatite/β-TCP/chitosan composites for tissue engineering applications

Calcium phosphate ceramics that mimic bone composition provide interesting possibilities for the advancement in bone tissue engineering. The present study reports on a chitosan composite reinforced by hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) obtained from waste mussel shells and cross-linked using tripolyphosphate (TPP). The ratios of the ceramic components in composites were 20/10/70, 30/20/50 and 40/30/30 (HA/β-TCP/CH, w/w %). Biodegradation rate, structural properties and in-vitro degradation of the bone-like composite scaffolds were investigated. The optimum amount of TPP required for composite was 2.5% and glycerol was used as plasticizer at an optimized concentration of 1%. Tripolyphosphate cross-linked chitosan composites were developed by freezing and lyophilisation. The Young's modulus of the scaffolds was increased from 4kPa to 17kPa and the porosity of composites dropped from 85 to 68% by increasing the HA/β-TCP ratio. After 28days in physiological solution, bone-like composite scaffolds with a higher ratio of HA/β-TCP (e.g. 40/30/30) showed about 2% lower biodegradation in comparison to scaffolds with a lower ratio of HA/β-TCP (i.e. 20/10/70). The obtained data suggest that the chitosan based bone-like composites could be potential candidates for biomedical applications.

A review of synthesis methods, properties and use of hydroxyapatite as a substitute of bone

In recent years, a significant achievement has been made in developing biomaterials, in particular the design of bioceramics, from natural sources for various biomedical applications. In this review, we discuss the fundamentals of structure, function and characteristics of human bone, its calcium and phosphate composition, role and importance of bioceramics for bone repairing or regeneration. This review also outlines various isolation techniques and the application of novel marine-derived hydroxyapatite (HA) and tri-calcium phosphate (TCP) for biocomposites engineering, and their potentials for bone substitute and bone regeneration. © (2015) Trans Tech Publications, Switzerland.

A novel squid pen chitosan/hydroxyapatite/β-tricalcium phosphate composite for bone tissue engineering

Squid pen chitosan was used in the fabrication of biocomposite scaffolds for bone tissue engineering. Hydroxyapatite (HA) and beta-tricalcium phosphate (β-TCP) obtained from waste mussel shells were used as the calcium phosphate source. The composite was prepared using 2.5% tripolyphosphate (TPP) and 1% glycerol as a cross-linker and plasticizer, respectively. The weight percent (wt.%) ratios of the ceramic components in the composite were 20/10/70, 30/20/50 and 40/30/30 (HA/β-TCP/Chi). The biodegradation rate and structural properties of the scaffolds were investigated. Scanning electron microscopy (SEM) and microCT(μCT) results indicated that the composites have a well defined lamellar structure with an average pore size of 200 μm. The porosity of the composites decreased from 88 to 56% by increasing the ratio of HA/β-TCP from 30 to 70%. After 28 days of incubation in a physiological solution, the scaffolds were degraded by approximately 30%. In vitro investigations showed that the composites were cytocompatible and supported the growth of L929 and Saos-2 cells. The obtained data suggests that the squid pen chitosan composites are potential candidates for bone regeneration. © 2015 Elsevier B.V. All rights reserved.

Microwave-assisted synthesis of high purity β-tricalcium phosphate crystalline powder from the waste of Green mussel shells (Perna canaliculus)

Beta-tricalcium phosphate (β-TCP) was successfully synthesized using the waste of Green mussel shells, Perna canaliculus. Calcined mussel shells and phosphoric acid were mixed in 1.5 Ca/P molar ratio and subjected to microwave irradiation (1100. W) for 30. min and subsequently calcined at 750. °C. The synthesized powder was chemically, compositionally and structurally characterized and was found to be very similar to a commercial β-TCP. Furthermore, the obtained powder was stable up to 1000. °C and lost only 2% of its weight. Its toxic metallic contents (e.g. Cd, Pb and As) were lower than standard limits for biogenic calcium phosphate for medical application. The synthesized β-TCP powder shows spherical morphology having diameter in the range of 100-150. nm and Ca/P molar ratio of 1.49, which is close to the stoichiometric ratio. The results obtained in this study showed that pure β-TCP can be produced from waste mussel shells in a simple and fast way using microwave irradiation. © 2014 Elsevier B.V.

Preparation and characterisation of irradiated crab chitosan and New Zealand Arrow squid pen chitosan

The properties of chitosan from Arrow squid (Nototodarus sloanii) pen (CHS) and commercial crab shell (CHC) were investigated using FTIR, DSC, SEM and XRD before and after irradiation at the dose of 28 kGy in the presence or absence of 5% water. Also, the viscosity, deacetylation degree, water and oil holding capacities, colour and antimicrobial activities of the chitosan samples were determined. Irradiation decreased (P < 0.05) the viscosity of CHC from 0.21 to 0.03 Pa s and of CHS from 1.71 to 0.23 Pa s. The inclusion of water had no effect on the viscosity of irradiated chitosan. Irradiation did not affect the degree of deacetylation of CHC, but increased the deacetylation degree of CHS from 72.78 to 82.29% in samples with 5% water. Water and oil holding capacities of CHS (1197.30% and 873.3%, respectively) were higher (P < 0.05) than those found in CHC (340.70% and 264.40%, respectively). The water and oil holding capacities were decreased for both types of chitosan irradiation, but were not affected by the addition of water. Squid pen chitosan was whiter in colour (White Index = 90.06%) compared to CHC (White Index = 83.70%). Generally, the CHC samples (control and irradiated) exhibited better antibacterial activity compared to CHS, but the opposite was observed with antifungal activity. © 2015 Elsevier B.V.

2014

Methylene blue removal from aqueous solution by Hylocereus undatus (dragon fruit) foliage

Dragon fruit foliage in its natural form was applied for decolorization of methyleneblue,a cationic dye from aqueous solution. The effects of major parameters like initial dye concentration, pH, adsorbent dose, temperature and contact time were investigated in batch experimental set-up. The optimum values for removal of methylene blue were identified to be pH 9.0 with 30 hours contact time using 1.2 g L−1biosorbent dosage at 250mg L−1 initial dye concentration. The present results suggested that foliage of dragon fruit can be a potential agricultural byproduct to be used as an environmental friendly and low cost biosorbent. © 2014 Trans Tech Publications, Switzerland.

2013

Removal Methyl Orange from Aqueous Solutions Using Dragon Fruit (Hylocereusundatus) Foliage

Biosorption of azoimide on almond integument: Kinetics, isotherm and thermodynamics studies

Hospital effluents are a serious problem in waterways due to azoimide that provides physical and health hazards. The removal of azoimide using powdered almond integument was studied in batch mode. Hydroxyl, carbonyl and carboxyl on the biosorbent surface were measured by titration method. The biosorption of azoimide was found to depend on the initial concentrations, pH and contact time. The equilibrium data was analyzed by using a non-linear form of Langmuir, Freundlich, Toth and Redlich-Peterson isotherm models. The fitness of data was evaluated using three error functions and correlation coefficient value (R 2). The error analysis showed three parameters models described the best biosorption in comparison of two parameters models such as Langmuir and Freundlich. The pseudo-first order, pseudo-second order and Elovich kinetic models were applied to study the kinetic behavior, and revealed applicability of the pseudo-second order model. The evaluation of thermodynamic parameters showed that biosorption process was endothermic and spontaneous. © 2013 Elsevier Ltd. All rights reserved.

2012

Eryngium foetidum L. Coriandrum sativum and Persicaria odorata L. : a review

Continuous metal and residual oil removal from palm oil mill effluent using natural zeolite-packed column

In this paper, fixed bed column studies were carried out to evaluate the performance of natural zeolite in removing heavy metals (Fe, Mn and Zn) and residual oil from palm oil mill effluent (POME) under varying experimental conditions such as flow rate and bed height. The maximum uptakes of Fe, Zn and Mn in a fixed bed adsorption column were 1.466, 0.203 and 0.019. mg/g at pH 6, bed height 15. cm and flow rate 3. ml/min,while maximum sorption of residual oil was 100. mg/g at pH 3 and same bed height and flow rate. Bohart-Adams and the bed depth service time (BDST) models were applied to the data for predicting breakthrough curves and to determine the characteristic parameters such as service time adsorption, adsorption rate, capacity and time required for 50% breakthrough. © 2012 Taiwan Institute of Chemical Engineers.

Removal of Fe (III), Mn (II) and Zn (II) from palm oil mill effluent (POME) by natural zeolite

The adsorption capacity of natural zeolite for the removal of heavy metal ions, zinc Zn(II), manganese Mn(II) and iron Fe(III), found in palm oil mill effluent was investigated in this study. The effects of contact time, agitation speed, pH, and sorbent dosage on the sorption of heavy metals were evaluated. The desorption potential of zeolite was also investigated. The sorption was fast with equilibrium reached within 180. min. The metal sorption increased with pH, and adsorption capacities ranged between 0.015 and 1.157. mg/g of zeolite. Equilibrium data followed the Langmuir isotherm model while the kinetic data were well described by the pseudo-second-order model. Maximum desorption was attained by HCl with 69.638, 58.575 and 61.516% of the initial adsorbed amount for Fe, Zn and Mn, respectively. More than 50% of Zn(II) and Mn(II) and about 60% of Fe(III) could be removed in the experiments. © 2012 Taiwan Institute of Chemical Engineers.

Removal of residual oils from palm oil mill effluent by adsorption on natural zeolite

The adsorption of residue oil from palm oil mill effluent using natural zeolite was investigated in this study. The adsorption was performed in batch mode, and the effect of different operational parameters such as pH, dose of adsorbent, stirring rate, contact time and initial oil concentration were explored. It was found that the pH plays a major role in the adsorption process. Isotherm data best fitted with the Freundlich model, and kinetic data followed the pseudo-second-order kinetic model. The results obtained demonstrated that the oil removal efficiencies by natural zeolite were up to 70 % at a pH of 3.0 and 50 min of contact time. The adsorbent material also has been characterised by X-ray diffraction, X-ray fluorescence and scanning electron microscopy. © 2012 Springer Science+Business Media B.V.

Process simulation and optimization of palm oil waste combustion using aspen plus

Simulation of hot gas desulfurization using liquid tin in scrubber