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.

Gas Therapy: Generating, Delivery, and Biomedical Applications.

Oxygen (O2 ), nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H2 S), and hydrogen (H2 ) with direct effects, and carbon dioxide (CO2 ) 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.

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.

Kiwi extract-incorporated poly(ɛ-caprolactone)/cellulose acetate blend nanofibers for healing acceleration of burn wounds.

Kiwi extract (KE) including different components such as quercetin, vitamins C and E, and actinides has been known as a debridement agent for burn wounds. In this study, electrospun poly(ɛ-caprolactone)/cellulose acetate blend nanofibers incorporating KE (PCL/CA/KE) were prepared and their performance was evaluated for healing acceleration of burn wounds. The physicochemical characterization of PCL/CA/KE nanofibers showed an average diameter of ∼420 nm, porosity of 70%, water contact angle of 61°, and water uptake of ∼220%. Moreover, the continuous release trend of KE from PCL/CA blend nanofibers happened during 24 h and the release mechanism was governed by the Fickian diffusion. Besides the cytocompatibility of PCL/CA/KE nanofibers, their in vivo experiments revealed that the bioactive wound dressing based on the sample has higher wound closure compared to KE after 21 days. Histopathology of wounds dressed by PCL/CA/KE nanofibers indicated epidermal formation along with a fully extended layer. Eventually, the obtained results confirmed that the PCL/CA/KE nanofibrous sample was a promising wound dressing for burn wound healing.

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.

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.

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.

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.

Conductive conduit based on electrospun poly (l-lactide-co-D, l-lactide) nanofibers containing 4-aminopyridine-loaded molecularly imprinted poly (methacrylic acid) nanoparticles used for peripheral nerve regeneration.

Using biocompatible polymer nanofibrous conduits with a controlled drug delivery have attracted much attention for peripheral nerve regeneration. This work was aimed at preparing electrospun poly (l-lactide-co-D, l-lactide) (PLDLLA) containing multi-walled carbon nanotubes (MWCNTs) and 4-aminopyridine (4-AP)-loaded molecularly imprinted nanoparticles (MIP4-AP) as well as evaluating their performance in in vitro and in vivo assessments. After synthesis of MIP4-AP based on poly (methacrylic acid) with imprinting factor of 1.78, it was incorporated into the PLDLLA/MWCNTs nanofibers to optimize. By adjusting the process variables, the average diameter and electrical conductivity of the nanofibrous sample were 92 nm and 2870 × 10-7 S cm-1, respectively. Afterward, 4-AP release of the optimum sample showed the presence of MIP4-AP leading to initial burst release decrease and plateau level postpone up to 96 h. Moreover, the culture results of PC12 as neuroblastoma cell line on optimal PLDLLA/MWCNTs/MIP4-AP nanofibrous sample revealed the highest cell proliferation without cytotoxicity compared to neat nanofibers. Eventually, the animal model experiment exhibited that the conductive conduit based on the optimum sample was able to repair the rat's sciatic nerve after four weeks in accordance with sciatic function index and histological studies.

Enhanced osteogenesis using poly (l-lactide-co-d, l-lactide)/poly (acrylic acid) nanofibrous scaffolds in presence of dexamethasone-loaded molecularly imprinted polymer nanoparticles.

The aim of this work is to prepare nanofibrous scaffolds based on poly (l-lactide-d, l-lactide)/poly (acrylic acid) [PLDLLA/PAAc] blends in the presence of Dexamethasone [Dexa]-loaded poly (2-hydroxyethyl methacrylate) [HEMA] as molecular imprinted polymer [MIP] nanoparticles [NPs] for enhancing osteogenesis. By adding 10 wt% of PAAc to the PLDLLA and employing response surface methodology, the average diameter of the electrospun nanofibers is approximately 237 nm. To increase the osteogenesis performance of the optimized nanofibrous scaffolds, the MIP nanoparticles are synthesized using HEMA monomer and Dexa template with a molar ratio of 10 to 1. Accordingly, these crosslinked drug nanocarriers exhibit an average diameter of around 122 nm and imprinting factor of approximately 1.8, enabling to adsorb Dexa molecules around 57%. Afterward, the Dexa-loaded MIP NPs have capability of a controlled drug release with ultimate value of 60% during 72 h. The simultaneous use of PLDLLA/PAAc-10 nanofibrous scaffold and Dexa-loaded MIP NPs within the cultivation media of fibroblast and mesenchymal stem cells is carried out by thiazolyl blue assay and acridine/ethidium bromide staining as well as alkaline phosphate/calcium content test, and alizarin red staining. The results reveal the remarkable efficiency of the blend nanofibers besides the MIP containing Dexa, thereby using for bone tissue engineering applications, potentially.

Antibacterial nanofibers based on poly(l-lactide-co-d, l-lactide) and poly(vinyl alcohol) used in wound dressings potentially: a comparison between hybrid and blend properties.

Morphology, hydrophilicity, degradation, mechanical properties, drug release, bacterial resistance, and cell viability are indispensable parameters for a bioactive wound dressing. In this work, the aforementioned terms between hybrid and blend nanofibrous samples based on poly (L-lactide-co-D, L-lactide) (PLDLLA) and poly (vinyl alcohol) (PVA) containing triclosan (Tri) as an antibacterial drug were investigated. The FE-SEM images showed that the presence of Tri in the hybrid and blend samples led to bimodal, and unimodal diameter size distributions. The FTIR spectra revealed that the addition of PVA caused to shift the carbonyl bond of PLDLLA in the blend sample, and DSC thermograms exhibited the immiscibility of PVA and PLDLLA polymers in the blend. Moreover, the hybrid sample showed higher hydrophilicity with water contact angle (WCA) of 53[Formula: see text] than the blend ones with WCA of 73[Formula: see text] which proved by water up-take test. In the following, the antibacterial evaluation showed better results for hybrid-Tri with the maximum growth inhibitory zones of 35 mm and 48 mm for E. coli and S. aureus, respectively. On the other hand, the hybrid nanofibrous sample showed remarkable mechanical properties (tensile stress ∼19 MPa, and Young's modulus ∼532 MPa). Finally, the SNL 76/7 fibroblast cell line culture confirmed that the hybrid-Tri nanofibrous sample had better proliferation performance than the blend-Tri sample because of the minimal cytotoxicity and maximal cell viability by MTT and acridine orange/ethidium bromide staining.

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.

Performance evaluation of poly (l-lactide-co-D, l-lactide)/poly (acrylic acid) blends and their nanofibers for tissue engineering applications.

Poly (l-lactide-co-D, l-lactide) (PLDLLA) is a biodegradable polymer predominantly used in biomedical applications. Despite unprecedented characteristics of PLDLLA, its wettability, mechanical properties, degradation, and cell attachment are main issues to improve. In this work, different blend films based on PLDLLA/poly (acrylic acid) (PAAc) are prepared to evaluate their miscibility, hydrophilicity, hydrolytic degradation and mechanical properties. For this purpose, a series of experiments such as DSC alongside SEM, water contact angle (WCA)/water up-take, weight measurements in phosphate buffer saline (PBS) and NaOH as well as tensile test are carried out. The DSC and SEM results show a miscibility for the blends, and hence by increasing PAAc, the WCA values and degradation rates are decreased and increased, respectively. Moreover, the degradation mechanisms of the blend samples follow surface/bulk erosion and bulk process in the alkaline and PBS environments, respectively. Subsequently, PLDLLA and its blends are electrospun to prepare nanofibrous samples, thereby assessing their cytotoxicity and cell viability by the use of thiazolyl blue assay and acridine orange/ethidium bromide staining, respectively. The in vitro SNL 76/7 fibroblast cells cultivation onto the surface of the blend with 10% wt. of PAAc revealed that this sample is a promising candidate for tissue engineering applications.