Search Results (421)

Recombinant protein hydrogels have emerged as transformative biomaterials that overcome the bioinertness and unpredictable degradation of traditional synthetic systems by leveraging genetically engineered backbones, such as elastin-like polypeptides, SF, and resilin-like polypeptides, to replicate extracellular matrix (ECM) dynamics and enable programmable functionality. Constructed through a hierarchical crosslinking strategy, these hydrogels integrate reversible physical interactions with covalent crosslinking approaches, collectively endowing the system with mechanical strength, environmental responsiveness, and controlled degradation behavior. Critically, molecular engineering strategies serve as the cornerstone for functional precision: domain-directed self-assembly exploits coiled-coil or β-sheet motifs to orchestrate hierarchical organization, while modular fusion of bioactive motifs through genetic encoding or site-specific conjugation enables dynamic control over cellular interactions and therapeutic release. Such engineered designs underpin advanced applications, including immunomodulatory scaffolds for diabetic wound regeneration, tumor-microenvironment-responsive drug depots, and shear-thinning bioinks for vascularized bioprinting, by synergizing material properties with biological cues. By uniting synthetic biology with materials science, recombinant hydrogels deliver unprecedented flexibility in tuning physical and biological properties. This review synthesizes emerging crosslinking paradigms and molecular strategies, offering a framework for engineering next-generation, adaptive biomaterials poised to address complex challenges in regenerative medicine and beyond. Full article

Marine biomass represents a valuable yet underexploited resource for the development of high-value biomaterials. Recent advances have highlighted the significant potential of marine-derived polysaccharides, proteins, and peptides in biomedical applications, most notably in drug delivery and wound healing. This review provides a comprehensive synthesis of current research on the extraction, processing and pharmaceutical valorization of these biopolymers, with a focus on their structural and functional properties that allow these materials to be engineered into nanocarriers, hydrogels, scaffolds, and smart composites. Key fabrication strategies such as ionic gelation, desolvation, and 3D bioprinting are critically examined for their role in drug encapsulation, release modulation, and scaffold design for regenerative therapies. The review also covers preclinical validation, scale-up challenges, and relevant regulatory frameworks, offering a practical roadmap from sustainable sourcing to clinical application. Special attention is given to emerging technologies, including stimuli-responsive biomaterials and biosensor-integrated wound dressings, as well as to the ethical and environmental implications of marine biopolymer sourcing. By integrating materials science, pharmaceutical technology and regulatory insight, this review aims to provide a multidisciplinary perspective for researchers and industrial stakeholders seeking sustainable and multifunctional pharmaceutical platforms for precision medicine and regenerative therapeutics. Full article

Background/Objectives: Gallic acid, a natural phenolic compound, was used as a crosslinking agent to achieve protein–polyphenol conjugation under alkaline conditions, presenting an innovative approach to stabilize gelatin. Methods: The formulated inks were evaluated for their rheological properties and 3D printing performance. Once the scaffolds were printed, physicochemical properties were assessed by color changes and FTIR. Additionally, three different post-processing methods were studied to avoid toxicity: incubation in PBS, incubation in NaOH followed by PBS neutralization, and incubation in HCl followed by PBS neutralization. Results: The inks exhibited shear-thinning behavior with self-supporting capacity after extrusion, indicating their suitability for use as inks in 3D printing. After printing, changes in color and in the amide I band/amide II band ratio were observed due to alkaline oxidation, confirming the gelatin crosslinking. Among the tested treatments, incubation in PBS or NaOH followed by neutralizing with PBS proved to be the most suitable for obtaining cytocompatible scaffolds. The mechanical properties demonstrated the suitability of the proposed crosslinking systems for creating scaffolds. Conclusions: This strategy confirms that gallic acid-mediated crosslinking under alkaline conditions enables the fabrication of cytocompatible and mechanically stable gelatin-based scaffolds, making them suitable for tissue engineering. Full article

Extracellular vesicles (EVs) have emerged as promising acellular tools for modulating immune responses for tissue engineering applications. This study explores the potential of human fibroblast-derived EVs delivered within a three-dimensional (3D) injectable scaffold composed of polycaprolactone (PCL) nanofibers and collagen (PNCOL) to reprogram macrophage behavior and support scaffold integrity under inflammatory conditions. EVs were successfully isolated from human fibroblasts using ultracentrifugation and characterized for purity, size distribution and surface markers (CD63 and CD9). Macrophage-laden PNCOL scaffolds were prepared under three conditions: macrophage-only (MP), fibroblast co-encapsulated (F-MP), and EV-encapsulated (EV-MP) groups. Structural integrity was assessed via scanning electron microscopy and Masson’s trichrome staining, while immunomodulatory effects were evaluated through metabolic assays, gene expression profiling, and immunohistochemistry for macrophage polarization markers (CD80, CD206). When co-encapsulated with pro-inflammatory (M1) macrophages in PNCOL scaffolds, fibroblast-derived EVs preserved scaffold structure and significantly enhanced macrophage metabolic activity compared to the control (MP) and other experimental group (F-MP). The gene expression and immunohistochemistry data demonstrated substantial upregulation of anti-inflammatory markers (TGF-β, CD163, and CCL18) and surface protein CD206, indicating a phenotypic shift toward M2-like macrophages for EV-encapsulated scaffolds relative to the other groups. The findings of this study demonstrate that fibroblast-derived EVs integrated into injectable PCL–collagen scaffolds offer a viable, cell-free approach to modulate inflammation, preserve scaffold structure, and support regenerative healing. This strategy holds significant promise for advancing immuno-instructive platforms in regenerative medicine, particularly in settings where conventional cell therapies face limitations in survival, cost, or safety. Full article

Type I collagen is a major protein in animals, and its hydrolyzed products, collagen peptides, have wide-ranging applications. This article reviews collagen peptides’ preparation methods, biological activities, and application progress in the fields of food, cosmetics, and medicine. By employing various extraction and hydrolysis methods, collagen peptides with different molecular weights can be obtained, and their biological activities are closely related to their molecular weight and amino acid sequence. Studies have revealed that collagen peptides possess a variety of biological activities, including antioxidant, hematopoietic promotion, osteogenic differentiation promotion, antihypertensive, and anti-diabetic effects. In the food industry, their antioxidant and hypoglycemic properties have opened new avenues for the development of healthy foods; in the cosmetics field, the moisturizing, anti-aging, and repair functions of collagen peptides are favored by consumers; in the medical field, collagen peptides are used in wound dressings, drug carriers, and tissue engineering scaffolds. Looking to the future, the development of green and efficient preparation technologies for collagen peptides and in-depth research into the relationship between their structure and function will be important research directions. The multifunctional properties of collagen peptides provide a broad prospect for their further application in the health industry. Full article

Since the mid-19th century, researchers have explored the potential of bio-based polymeric materials for diverse applications, with particular promise in medicine. This review provides a focused and detailed examination of natural and synthetic biopolymers relevant to tissue engineering and biomedical applications. It emphasizes the structural diversity, functional characteristics, and processing strategies of major classes of biopolymers, including polysaccharides (e.g., hyaluronic acid, alginate, chitosan, bacterial cellulose) and proteins (e.g., collagen, silk fibroin, albumin), as well as synthetic biodegradable polymers such as polycaprolactone, polylactic acid, and polyhydroxybutyrate. The central aim of this manuscript is to elucidate how intrinsic properties—such as molecular weight, crystallinity, water retention, and bioactivity—affect the performance of biopolymers in biomedical contexts, particularly in drug delivery, wound healing, and scaffold-based tissue regeneration. This review also highlights recent advancements in polymer functionalization, composite formation, and fabrication techniques (e.g., electrospinning, bioprinting), which have expanded the application potential of these materials. By offering a comparative analysis of structure–property–function relationships across a diverse range of biopolymers, this review provides a comprehensive reference for selecting and engineering materials tailored to specific biomedical challenges. It also identifies key limitations, such as production scalability and mechanical performance, and suggests future directions for developing clinically viable and environmentally sustainable biomaterial platforms. Full article

Hydrogels have emerged as multifunctional biomaterials in cardiac surgery, offering promising solutions for myocardial regeneration, adhesion prevention, valve engineering, and localized drug and gene delivery. Their high water content, biocompatibility, and mechanical tunability enable close emulation of the cardiac extracellular matrix, supporting cellular viability and integration under dynamic physiological conditions. In myocardial repair, injectable and patch-forming hydrogels have been shown to be effective in reducing infarct size, promoting angiogenesis, and preserving contractile function. Hydrogel coatings and films have been designed as adhesion barriers to minimize pericardial adhesions after cardiotomy and improve reoperative safety. In heart valve and patch engineering, hydrogels contribute to scaffold design by providing bio-instructive, mechanically resilient, and printable matrices that are compatible with 3D fabrication. Furthermore, hydrogels serve as localized delivery platforms for small molecules, proteins, and nucleic acids, enabling sustained or stimuli-responsive release while minimizing systemic toxicity. Despite these advances, challenges such as mechanical durability, immune compatibility, and translational scalability persist. Ongoing innovations in smart polymer chemistry, hybrid composite design, and patient-specific manufacturing are addressing these limitations. This review aims to provide an integrated perspective on the application of hydrogels in cardiac surgery. The relevant literature was identified through a narrative search of PubMed, Scopus, Web of Science, Embase, and Google Scholar. Taken together, hydrogels offer a uniquely versatile and clinically translatable platform for addressing the multifaceted challenges of cardiac surgery. Hydrogels are poised to redefine clinical strategies in cardiac surgery by enabling tailored, bioresponsive, and functionally integrated therapies. Full article

Innovative changes to our current food system are needed, and one solution is cultivated meat, which uses modern engineering, materials science, and biotechnology to produce animal protein. This article highlights the advantages of incorporating whey protein isolate (WPI) and β-lactoglobulin (β-LG) into hydrogel networks to aid cell growth on cultivated meat scaffolds. The protein and polysaccharide (i.e., alginate) components of the scaffolds are food-grade and generally regarded as safe ingredients, enabling the transition to more food-safe, edible, and nutritious scaffolds. The impact of WPI and varying properties on cell performance was evaluated; alginate concentration and the addition of proteins into the hydrogels significantly altered their stiffness and strength. The results of this study demonstrate the innocuous nature of novel scaffolds and reveal enhanced cell proliferation on WPI and β-LG-modified groups compared to standard biomaterial controls. This work serves as a stepping stone for more comprehensive analyses of WPI, β-LG, and alginate scaffolds for use in cultivated meat research and production. Full article

The cryopreservation of three-dimensional (3D) biofabricated constructs is a key enabler for their clinical application in regenerative medicine. Unlike two-dimensional (2D) cultures, 3D systems such as encapsulated cell spheroids, molded hydrogels, and bioprinted tissues present specific challenges related to cryoprotectant (CPA) diffusion, thermal gradients, and ice formation during freezing and thawing. This review examines the current strategies for preserving 3D constructs, focusing on the role of biomaterials as cryoprotective matrices. Natural polymers (e.g., hyaluronic acid, alginate, chitosan), protein-based scaffolds (e.g., silk fibroin, sericin), and synthetic polymers (e.g., polyethylene glycol (PEG), polyvinyl alcohol (PVA)) are evaluated for their ability to support cell viability, structural integrity, and CPA transport. Special attention is given to cryoprotectant systems that are free of dimethyl sulfoxide (DMSO), and to the influence of hydrogel architecture on freezing outcomes. We have compared the efficacy and limitations of slow freezing and vitrification protocols and review innovative approaches such as temperature-controlled cryoprinting, nano-warming, and hybrid scaffolds with improved cryocompatibility. Additionally, we address the regulatory and manufacturing challenges associated with developing Good Manufacturing Practice (GMP)-compliant cryopreservation workflows. Overall, this review provides an integrated perspective on material-based strategies for 3D cryopreservation and identifies future directions to enable the long-term storage and clinical translation of engineered tissues. Full article

Keratin, a fibrous structural protein, has been employed as a biomaterial for hemostasis and tissue repair due to its structural stability, mechanical strength, biocompatibility, and biodegradability. While extensive research has focused on developing scaffolds using keratin extracted from various sources, no studies to date have explored the use of keratin derived from human nail clippings. In this study, keratin was extracted from human nail clippings using the Shindai method and used to fabricate and compare two types of scaffolds for bone tissue engineering via the freeze-drying method. The first scaffold consisted of keratin combined with gelatin (KG), while the second combined keratin, gelatin, and hydroxyapatite (HAp) (KGH), the latter synthesized from blood cockle clam shells using the wet precipitation method. Physicochemical characterization and surface morphology analysis of keratin and both scaffolds showed promising results. Tensile strength testing revealed a significant difference in Young’s modulus. The KG scaffold exhibited higher porosity, water uptake, and water retention capacity compared to the KGH scaffold. In vitro biocompatibility studies revealed that the KGH scaffold supported higher cell proliferation compared to the KG scaffold. This study demonstrates the potential of using human nail-derived keratin in composite scaffold fabrication and serves as a foundation for future research on this novel biomaterial source. Full article

Bone repair and regeneration following an injury still present challenges worldwide. Three-dimensional (3D) scaffolds made from various materials are used for bone tissue engineering (BTE) applications. Polymers, minerals and nanotechnology are now being used in combination to achieve specific goals for BTE, including the delivery of antimicrobials through the scaffolds to prevent post-surgical infection. While several materials are utilised for BTE, natural polymers present a unique set of materials that can be manipulated to formulate scaffolds for BTE applications. They have been found to demonstrate higher biocompatibility, biodegradability and lower toxicity. Some even naturally mimic the bone microarchitecture, providing inherent structural support for BTE. Natural polymers may be simply classified as those from plant and animal sources. From both sources, there are different types of proteins, polysaccharides and other specialised materials that are already in use for research in BTE. Interestingly, these have the potential to revolutionise the field of BTE with a sustainable approach. In this review, we first discuss the different natural polymers used in BTE from plant sources, followed by animal sources. We then explore novel materials that are aimed at sustainable approaches, focusing on innovation from the last decade. In these sections, we outline studies of these materials with different types of bone cells, including bone marrow mesenchymal stromal cells (MSCs), which are the progenitors of bone. We finally outline the limitations, conclusions and future directions from our perspective in this dynamic field of polymers in BTE. With this review, we hope to bring together the updated existing knowledge and the potential future of innovation and sustainability in natural polymers for biomimetic BTE applications for fellow scientists, researchers and surgeons in the field. Full article

Materials formed with a base of silk fibroin (SF) are successfully used in tissue engineering since their properties are similar to those of natural extracellular matrixes. Mixing SF with different polymers, for example, polyethylene oxide (PEO) and polyvinylpyrrolidone (PVP), allows the production of fibers, hydrogels, and films and their morphology to be controlled. The impact of PEO and PVP on formation and structure of SF adsorption layers was studied at different was studied at different polymer concentrations (from 0.002 to 0.5 mg/mL) and surface lifetimes. The protein concentration was fixed at 0.02 and 0.2 mg/mL. These concentrations are characterized by different types of spontaneously formed structures at the air–water interface. Since both synthetic polymers possess surface activity, they can penetrate the fibroin adsorption layer, leading to a decrease in the dynamic surface elasticity at almost constant surface tension and a decrease in ellipsometric angle Δ and adsorption layer thickness. As shown by AFM, the presence of polymers increases the porosity of the adsorption layer, due to the possible arrangement of protein and polymer molecules into separate domains, and can result in various morphology types such as fibers or tree-like ribbons. Therefore, polymers like PEO and PVP can be used to regulate the SF self-assembly at the interface, which in turn can affect the properties of the materials with high surface areas like electrospun matts and scaffolds. Full article

Large segmental bone defects present significant challenges due to the insufficient vascularization of implanted grafts, necessitating advances in vascularized bone tissue engineering. Recent innovations focus primarily on enhancing graft vascularization through advanced biomaterial scaffolds, precise three-dimensional (3D) bioprinting technologies, biochemical interventions, and co-culture techniques. Biomaterial scaffolds featuring microchannels and high-surface-area architectures facilitate endothelial cell infiltration and subsequent vessel formation. Concurrently, sophisticated 3D-bioprinting methods, including inkjet, extrusion, and laser-assisted approaches, enable the precise placement of endothelial and osteogenic cells, promoting anatomically accurate vascular networks. Biochemical strategies that utilize the simultaneous delivery of angiogenic factors (e.g., vascular endothelial growth factor) and osteogenic factors (e.g., bone morphogenetic protein-2) effectively couple angiogenesis and osteogenesis. Additionally, co-culturing mesenchymal stem cells and endothelial progenitors accelerates the development of functional capillary networks. Preclinical studies consistently demonstrate superior outcomes for prevascularized grafts, as evidenced by enhanced vascular inosculation, increased bone formation, and improved mechanical stability compared to non-vascularized controls. These technological advancements collectively represent significant progress toward the clinical translation of engineered vascularized bone grafts capable of addressing complex and previously intractable bone defects. Full article

Chronic wounds represent a major clinical challenge due to their prolonged healing process and susceptibility to bacterial colonization, particularly by biofilm-forming bacteria. To address these issues, in this work, silver-treated silk fibroin scaffolds were developed and tested as multifunctional wound dressings, combining antimicrobial and regenerative properties. Silk fibroin, a natural protein derived from Bombyx mori cocoons, is widely recognized for its biocompatibility and suitability for tissue engineering. In this study, porous silk fibroin scaffolds were functionalized with silver nanoparticles through a photo-reduction process and were comprehensively tested for their cytocompatibility and wound healing potential. The excellent antibacterial activity of the silver-treated scaffolds was demonstrated against Escherichia coli and antibiotic-resistant Pseudomonas aeruginosa, as was extensively reported in a previous work. Biological assays were performed using 3T3 fibroblasts cultured on both untreated and silver-treated silk fibroin scaffolds. Biocompatibility assays, such as MTT, Live/Dead, and cytoskeleton analyses, demonstrated biocompatibility in both scaffold types, comparable to the control. Wound healing potential was assessed using in vitro scratch assays, revealing full wound closure (100%) after 24 h in cells cultured with untreated and silver-treated silk fibroin scaffolds, in contrast to 78.5% closure in the control. Notably, silver-treated scaffolds exhibited enhanced fibroblast repopulation within the wound gap, suggesting a synergistic effect of silver and fibroin in promoting tissue regeneration. These findings demonstrate that silver-treated silk fibroin scaffolds possess both anti-microbial and regenerative properties, making them promising candidates for chronic wound management applications. Full article

This study evaluated the biological performance in vitro of two 3D-printed hydroxyapatite (HA) and polylactic acid (PLA) composite scaffolds with two different infill densities (50% [HA-PLA50] and 70% [HA-PLA70]). Comparative analysis using MG-63 cell cultures evaluated the following: (1) integrity after exposure to various sterilization methods; (2) cell viability; (3) morphological characteristics; (4) cell proliferation; (5) cytotoxicity; (6) gene expression; and (7) protein synthesis. Ultraviolet radiation was the preferred sterilization method. Both scaffolds maintained adequate cell viability and proliferation over 7 days without significant differences in cytotoxicity. Notably, HA-PLA50 scaffolds demonstrated superior osteogenic potential, showing a significantly higher expression of collagen type I (COL1A1) and an increased synthesis of interleukins 6 and 8 (IL-6, IL-8) compared to HA-PLA70 scaffolds. While both scaffold types supported robust cell growth, the HA-PLA50 formulation exhibited enhanced bioactivity, suggesting a potential advantage for bone tissue engineering applications. These findings provide important insights for optimizing 3D-printed bone graft substitutes. Full article