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Keywords = silk fibroin composite scaffolds

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14 pages, 274 KB  
Systematic Review
Biomechanical Properties of Silk-Derived 3D Bioprinted Scaffolds for Cartilage Regeneration: A Comprehensive Review
by Sanjana Challa, Alynah J. Adams, Laken Anderson, Bria Fiebiger, Rikin Soni, Athena Ye, Jocelyn Hunt, Charlotte Thomas, Dorien I. Schonebaum, Jose A. Foppiani, Umar Choudry and Samuel J. Lin
Biomimetics 2026, 11(8), 575; https://doi.org/10.3390/biomimetics11080575 - 12 Aug 2026
Viewed by 300
Abstract
Cartilage regeneration remains a major clinical challenge because cartilage has limited healing capacity and must withstand substantial mechanical loading. Silk fibroin, a cocoon-derived biomaterial with tunable mechanical properties, has emerged as a promising scaffold material for cartilage tissue engineering. This systematic review evaluates [...] Read more.
Cartilage regeneration remains a major clinical challenge because cartilage has limited healing capacity and must withstand substantial mechanical loading. Silk fibroin, a cocoon-derived biomaterial with tunable mechanical properties, has emerged as a promising scaffold material for cartilage tissue engineering. This systematic review evaluates the biomechanical performance, fabrication approaches, and regenerative potential of silk fibroin bioprinted scaffolds for cartilage repair. A systematic review was conducted according to PRISMA guidelines. Primary outcomes included scaffold mechanical properties relevant to cartilage function. Secondary outcomes included scaffold composition, fabrication methods, biological performance, clinical applications, and reported limitations. Of 918 identified records, 24 studies published between 2014 and 2025 met the inclusion criteria. Most were preclinical studies using silk fibroin-based hydrogels, often combined with hyaluronic acid, gelatin, collagen, or synthetic polymers. Mechanical properties varied according to scaffold composition and crosslinking methods. Reinforced scaffolds generally demonstrated improved stiffness, structural support, and load distribution. Silk fibroin scaffolds consistently supported chondrogenesis and cartilage-like tissue formation. However, challenges remain, including mechanical mismatch with native cartilage, construct instability, cell loss, and suboptimal degradation profiles. Overall, silk fibroin bioprinted scaffolds demonstrated support for chondrogenesis and cartilage-like tissue formation in preclinical studies for cartilage regeneration. Future research should focus on standardized biomechanical testing, long-term in vivo evaluation, and clinically relevant scaffold designs to facilitate translation toward functional cartilage repair. Full article
(This article belongs to the Special Issue Silk-Based Bioinspired Materials: Design and Application 2026)
29 pages, 6237 KB  
Article
Comparison of EDC/NHS and Pentasodium Triphosphate (TPP) as Cross-Linking Agents for Nanohydroxyapatite, Silk Fibroin, and Chitosan 3D Scaffolds
by Anna Tuwalska, Alina Sionkowska, Grzegorz Tylko, Maciej Przybyłek, Anna Maria Osyczka, Iwona Białas and Michele Laus
Polymers 2026, 18(13), 1610; https://doi.org/10.3390/polym18131610 - 28 Jun 2026
Viewed by 950
Abstract
The present study compares two scaffold cross-linking strategies, EDC/NHS and pentasodium triphosphate (TPP), applied to nanohydroxyapatite/silk fibroin/chitosan (nHA/SF/CTS) scaffolds. The effects of the cross-linking strategy on scaffold morphology, ATR-FTIR profile, swelling, in vitro degradation, and compressive properties were evaluated. In addition, the biological [...] Read more.
The present study compares two scaffold cross-linking strategies, EDC/NHS and pentasodium triphosphate (TPP), applied to nanohydroxyapatite/silk fibroin/chitosan (nHA/SF/CTS) scaffolds. The effects of the cross-linking strategy on scaffold morphology, ATR-FTIR profile, swelling, in vitro degradation, and compressive properties were evaluated. In addition, the biological response of selected 20:40:40 and 15:70:15 (w/w) scaffold variants was assessed using SaOS-2 cells. The IR spectra of TPP- and EDC/NHS-cross-linked materials were qualitatively similar, and no distinct bands attributable to residual EDC or NHS were observed after washing. SEM observations indicated that the TPP-cross-linked scaffolds tended to have smaller and more spherical pores, whereas the EDC/NHS-cross-linked materials showed a more elongated pore morphology. These qualitative morphological differences were accompanied by differences in swelling, degradation, and low-strain mechanical response. The 20:40:40 formulation cross-linked with EDC/NHS showed the most favorable low-strain response, whereas PBS swelling markedly reduced the early compressive response of all scaffolds. Biological assessment showed that the 20:40:40 scaffolds supported viable SaOS-2 populations and maintained osteogenic activity, although cell colonization remained lower than on the control surfaces. The 15:70:15 variant performed less favorably, particularly after TPP cross-linking. These findings indicate that both cross-linking strategies can be used to obtain nHA/SF/CTS scaffolds, but their effects depend strongly on scaffold composition and on the property being considered. Full article
(This article belongs to the Special Issue Advanced Polymer Processing for Tissue Engineering)
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27 pages, 2808 KB  
Review
3D Printing of Biopolymer-Based Scaffolds for Bone Tissue Engineering: Materials, Fabrication, and Translational Strategies
by Yeajin Song, Hongyoon Kim and Seunghun S. Lee
Molecules 2026, 31(13), 2206; https://doi.org/10.3390/molecules31132206 - 23 Jun 2026
Cited by 1 | Viewed by 620
Abstract
Bone defects from trauma, tumour resection, infection, and degenerative disease remain a major clinical burden, and autografts face limitations of supply and donor-site morbidity. Three-dimensional (3D) printing offers a route to patient-specific, architecturally defined bone scaffolds, while biopolymers from natural sources provide biodegradability, [...] Read more.
Bone defects from trauma, tumour resection, infection, and degenerative disease remain a major clinical burden, and autografts face limitations of supply and donor-site morbidity. Three-dimensional (3D) printing offers a route to patient-specific, architecturally defined bone scaffolds, while biopolymers from natural sources provide biodegradability, biocompatibility, and extracellular matrix-mimicking cues consistent with sustainable, green biomaterials science. This review synthesises recent progress in 3D printing of biopolymer-based scaffolds for bone tissue engineering. We first examine the principal feedstocks—alginate, gelatin and gelatin methacryloyl, collagen, chitosan, silk fibroin, cellulose, and microbial polyesters—and their preparation, crosslinking chemistry, and printability. We then compare extrusion, light-based, and indirect printing technologies and the process–property relationships governing resolution, mechanical competence, and cell viability. Composite and functionalisation strategies, including biopolymer–bioceramic hybrids and controlled delivery of growth factors and antimicrobial agents, are analysed as routes to osteoinduction, vascularisation, and infection control. Finally, we evaluate translational performance in preclinical models and outline central challenges of vascularisation, mechanical–degradation matching, scalability, and regulatory standardisation. Biopolymer 3D printing is positioned as a ve rsatile, sustainable platform whose clinical maturation depends on integrated material, structural, and biological design. Full article
(This article belongs to the Special Issue Biopolymer-Based Materials: Preparation, Properties and Applications)
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21 pages, 4581 KB  
Article
Chitosan–Silk Fibroin Hydrogel Scaffold Incorporating Bioactive Aloe vera and Mimosa Complex for Cartilage-Supportive Applications
by Witwisitpong Maneechan, Areeya Tuanchai, Sukunya Ross, Gareth M. Ross, Chatnarong Putthong, Jatuporn Ngoenkam, Yuriko Higuchi, Pensri Charoensit and Jarupa Viyoch
Polymers 2026, 18(11), 1406; https://doi.org/10.3390/polym18111406 - 5 Jun 2026
Viewed by 700
Abstract
A composite hydrogel scaffold comprising chitosan, silk fibroin, Aloe vera extract, and Mimosa complex was fabricated and thoroughly characterized. Upon freeze-drying, the scaffolds displayed a uniform cylindrical geometry with a highly porous, interconnected polymeric network. Quantitative image analysis revealed a mean pore diameter [...] Read more.
A composite hydrogel scaffold comprising chitosan, silk fibroin, Aloe vera extract, and Mimosa complex was fabricated and thoroughly characterized. Upon freeze-drying, the scaffolds displayed a uniform cylindrical geometry with a highly porous, interconnected polymeric network. Quantitative image analysis revealed a mean pore diameter of 43.09 ± 2.27 µm alongside an overall porosity of 61.4 ± 6.2%. ATR-FTIR and XRD analyses confirmed successful inclusion of the complex formation and the incorporation of all constituents into the final formulation. The scaffold exhibited a compressive modulus of 46.63 ± 22.71 kPa (dry) and 5.40 ± 3.73 kPa (hydrated), with a swelling ratio of 756.62 ± 114.08%, supporting its suitability for physiological applications. TGF-β3 loading via adsorption yielded an entrapment efficiency of approximately 79.18%, reflecting effective physical immobilization throughout the polymer matrix. Cytocompatibility was subsequently assessed using an indirect contact model combined with an MTT assay, both of which confirmed that TGF-β3-loaded scaffolds exerted no cytotoxic effects on chondrocytes. After 28 days in culture, scanning electron microscopy revealed pronounced cell adhesion, preservation of rounded cell morphology, and ECM deposition along pore walls and throughout interconnected channels. Immunofluorescence analysis further demonstrated a time-dependent accumulation of aggrecan and collagen type II within the three-dimensional scaffold architecture. Collectively, these findings suggest that the developed composite hydrogel scaffold is well-suited for cartilage-related in vitro culture applications. Full article
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33 pages, 9605 KB  
Review
Silk-Derived 3D-Bioprinted Scaffolds for Neural Repair and Nerve Regeneration: A Comprehensive Review
by Alynah J. Adams, Sanjana Challa, Cynthia Yan, Isabella Beltz, Alexa Kambol, Kaavian Shariati, Jocelyn Hunt, Charlotte Thomas, Dorien I. Schonebaum, Jose A. Foppiani, Umar Choudry and Samuel J. Lin
Life 2026, 16(6), 892; https://doi.org/10.3390/life16060892 - 26 May 2026
Viewed by 577
Abstract
Traumatic injuries often result in nerve tissue damage and functional deficits due to limited regeneration. Silk fibroin, a biopolymer with inherent biocompatibility and tunable properties, is a promising material for 3D-bioprinted neural tissue scaffolds. This review highlights recent advancements in silk-derived composite scaffolds, [...] Read more.
Traumatic injuries often result in nerve tissue damage and functional deficits due to limited regeneration. Silk fibroin, a biopolymer with inherent biocompatibility and tunable properties, is a promising material for 3D-bioprinted neural tissue scaffolds. This review highlights recent advancements in silk-derived composite scaffolds, often incorporating additional materials like collagen or conductive polymers to enhance their performance. This review examines how material composition, scaffold architecture, and fabrication strategy influence biological response and functional recovery. This comprehensive review follows PRISMA guidelines and uses comprehensive searches of PubMed, MEDLINE, Embase, Web of Science, Cochrane Central, and ClinicalTrials.gov for studies published through 2025. Studies were screened for eligibility based on substance type, mechanical properties, production methods, and outcomes. Findings were synthesized qualitatively. Twelve studies were included, comprising rat (50%), canine (8.3%), and in vitro (41.7%) models. Analysis reveals that silk fibroin acts as a highly adaptable mechanical backbone. It can consistently integrate with bioactive additives (collagen, dECM) or conductive polymers (Polypyrrole, MXene) to meet specific therapeutic demands. For spinal cord injuries, composites reached a compressive modulus capable of resisting physiological pressures and preventing scaffold collapse. In soft tissue applications, silk–hydrogel blends provided localized release of exosomes and small molecules during the acute injury phase, reducing neuroinflammatory markers. Additionally, adding conductive materials allowed the scaffolds to bridge electrical gaps and promote Schwann cell proliferation and neuronal differentiation. Furthermore, 3D bioprinting enabled the creation of defined microchannels that replicate native fascicular architecture. In vivo outcomes consistently showed superior axonal regeneration, myelination, and synaptic reconnection compared to controls, correlating with significant improvements in electrophysiological and motor function. This review highlights the clinical potential of silk fibroin-based 3D-printed biomaterials for nerve regeneration, including neural repair and neural tissue engineering. More recent studies place greater emphasis on integrating mechanical, architectural, and biological considerations into scaffold design, resulting in increasingly multifunctional scaffold systems. Despite promising efficacy, the heterogeneity of fabrication methods and the predominance of rodent models highlight the need for standardized protocols and evaluations in relevant models to facilitate clinical translation. Full article
(This article belongs to the Section Medical Research)
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22 pages, 15964 KB  
Article
Cryogenic Foaming of Silk Fibroin Composite for Scaffolds in Bone and Periodontal Regeneration
by Giuseppe De Giorgio, Barbara Medagli, Biagio Matera, Katia Rupel, Giuseppe Tarabella, Gianluca Turco, Maddalena Manfredi, Benedetta Ghezzi and Pasquale D’Angelo
J. Funct. Biomater. 2026, 17(5), 230; https://doi.org/10.3390/jfb17050230 - 6 May 2026
Viewed by 1993
Abstract
Bone tissue has a remarkable regenerative capacity; however, advanced strategies are needed to support the repair process for critical-sized defects. While autografts and allografts remain the gold standard, their limitations have stimulated alternative approaches in bone tissue engineering, in search of scaffolds capable [...] Read more.
Bone tissue has a remarkable regenerative capacity; however, advanced strategies are needed to support the repair process for critical-sized defects. While autografts and allografts remain the gold standard, their limitations have stimulated alternative approaches in bone tissue engineering, in search of scaffolds capable of mimicking native bone properties to promote effective regeneration. In this study, silk fibroin (SF)-based composite scaffolds incorporating β-tricalcium phosphate (β-TCP) and poly-ε-caprolactone (PCL) were synthesized using a simple and innovative cryogenic foaming method. The proposed fabrication technique overcomes many limitations of current synthesis methods, such as long processing times, the use of solvents, and reliance on complex, energy-intensive equipment. The composites were characterized using infrared spectroscopy to confirm the incorporation of all three components and their chemical bond arrangements. µ-CT, SEM, and ESEM analyses revealed that SF/β-TCP/PCL scaffolds exhibited great porosity and dynamic interaction with water while preserving pore morphology in wet environments. Swelling behavior, indirect cytotoxicity, and cell proliferation tests recognized the greater performance of SF/β-TCP/PCL scaffolds in promoting long-term cell proliferation, maintaining superior mechanical properties. These findings indicate that the proposed original, simple, and relatively low-cost manufacturing approach enabled the fabrication of scaffolds with excellent mechanical performances, controlled and stable porosity under both dry and physiological-like conditions, and high biocompatibility. The resulting constructs demonstrated promising results for cell proliferation and osteoconductive behavior, supporting their potential suitability as artificial bone substitutes. Full article
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38 pages, 1659 KB  
Review
Natural Polymers in Tissue Engineering and Regeneration: Material–Cell Mechanotransduction, Biofabrication Strategies, and Clinical Translation
by Gabriela Calin, Mihnea Costescu, Marcela Nour, Camer Salim, Nicu Ovidiu Lungu, Alina Stefanache, Roman Rusnac, Elena Costescu, Mihai Cozmin, Petruta Iuliana Moraru, Alina Mitocaru, Tatiana Iov and Letiția Doina Duceac
Biomedicines 2026, 14(4), 843; https://doi.org/10.3390/biomedicines14040843 - 8 Apr 2026
Cited by 6 | Viewed by 1714
Abstract
Fractures are becoming a bigger and bigger global health problem, with an estimated 178 million new cases each year and 455 million people living with disabilities caused by fractures. Donor site morbidity, the risk of immune rejection, and limited functional integration all make [...] Read more.
Fractures are becoming a bigger and bigger global health problem, with an estimated 178 million new cases each year and 455 million people living with disabilities caused by fractures. Donor site morbidity, the risk of immune rejection, and limited functional integration all make current grafting techniques less effective. Biomaterials that come from nature, like collagen, gelatin, chitosan, alginate, hyaluronic acid (HA), and silk fibroin, have become promising scaffolds because they are bioactive, mimic the extracellular matrix (ECM), and can be broken down by enzymes. Crosslinking and composite reinforcement can greatly change how well they work. For example, collagen scaffolds that are highly crosslinked with glutaraldehyde keep up to 51.9% of their tensile strength after being exposed to enzymes, while non-crosslinked scaffolds only keep 12% of their strength. Chitosan–hydroxyapatite matrices, on the other hand, can reach compressive strengths of 2–12 MPa, which is close to the strength of cancellous bone. Additive manufacturing and 4D printing allow for precise control of structures and the ability to change their shape over time, which helps with vascularization and mechanical adaptation. Injectable and in situ-forming hydrogels show clinically important results, such as filling 85% of osteochondral defects in rabbits, improving left ventricular ejection fraction by up to 9% in large-animal cardiac models, and speeding up healing by 25–40% in chronic wounds. Even with these improvements, it is still hard to get batch consistency, a standardized way to test mechanical properties, and production that meets GMP (Good Manufacturing Practices) standards and can be scaled up. Full article
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17 pages, 2420 KB  
Article
Bovine Cartilage-Derived Type II Collagen Composite Scaffolds: Collagen Characterization, Physicochemical Properties, and In Vitro Chondrocyte Responses
by Zihan Zhu, Ming Ju, Min Li and Wangang Zhang
J. Funct. Biomater. 2026, 17(3), 116; https://doi.org/10.3390/jfb17030116 - 28 Feb 2026
Cited by 1 | Viewed by 1630
Abstract
Type II collagen (CII), the major structural protein in the cartilage extracellular matrix, is a promising biomaterial for scaffold design in cartilage tissue engineering. In this study, high-purity CII was successfully extracted from bovine cartilage, an abundant by-product of cattle slaughter, and its [...] Read more.
Type II collagen (CII), the major structural protein in the cartilage extracellular matrix, is a promising biomaterial for scaffold design in cartilage tissue engineering. In this study, high-purity CII was successfully extracted from bovine cartilage, an abundant by-product of cattle slaughter, and its amino acid composition, triple-helical conformation, and thermal stability were verified. CII was subsequently combined with silk fibroin (SF) and chitosan (CS) to fabricate three-dimensional (3D) porous scaffolds via freeze-drying. The pore structure, porosity, swelling behavior, mechanical properties and in vitro degradation characteristics were systematically evaluated. Scaffolds with favorable structural integrity, mechanical performance, and degradation rates were further evaluated biologically using human primary chondrocytes. All CII-based composite scaffolds supported chondrocyte growth and promoted early extracellular matrix deposition. Notably, the scaffold with a CII:SF:CS ratio of 7:3:1 showed the highest GAG/DNA content, accompanied by upregulated gene expression related to the cartilage phenotype (COL2A1, ACAN, and SOX9) and reduced expression of the dedifferentiation marker COL1A1, indicating improved phenotype maintenance. Overall, within the tested range, CII70 (CII:SF:CS = 7:3:1) represents a practical compromise between scaffold stability and in vitro chondrocyte-related outcomes, providing a basis for selecting CII/SF/CS formulations for cartilage tissue engineering. Full article
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38 pages, 4278 KB  
Review
Fibrous Biomaterial Scaffold for Tympanic Membrane Repair: Microarchitectural Engineering and Structure Function Performance
by Lea Jiang, Chokri Cherif and Michael Wöltje
J. Funct. Biomater. 2026, 17(1), 53; https://doi.org/10.3390/jfb17010053 - 21 Jan 2026
Cited by 2 | Viewed by 1982
Abstract
Tympanic membrane (TM) perforations, arising from infections, injuries, or chronic otitis media, remain a frequent clinical finding and can lead to hearing problems when the tissue does not regenerate adequately. Although autologous grafts are still the standard option for repairing persistent defects, they [...] Read more.
Tympanic membrane (TM) perforations, arising from infections, injuries, or chronic otitis media, remain a frequent clinical finding and can lead to hearing problems when the tissue does not regenerate adequately. Although autologous grafts are still the standard option for repairing persistent defects, they come with well-known limitations. Beyond the need for additional harvesting procedures, these grafts rarely reproduce the intricate, fibrous layering of the native TM, which can compromise sound transmission after healing. In search of alternatives, fibre-based scaffolds have attracted considerable interest. The primary advantage of this material is the level of structural control it affords. The fibre orientation, porosity, and overall microarchitecture can be adjusted to replicate the organisation and mechanical behaviour of the natural membrane. A range of biocompatible polymers—among them silk fibroin, poly(ε-caprolactone), poly(lactic acid), and poly(vinyl alcohol) and their composites—provide options for tuning stiffness, degradation rates, and interactions with cells, making them suitable building blocks for TM repair constructs. This review provides a comprehensive overview of contemporary fabrication methodologies, namely electrospinning, additive manufacturing, melt electrowriting, and hybrid strategies. In addition, it offers a detailed discussion of the evaluation procedures employed for these scaffolds and discusses how scaffold structure affects later performance. Mechanical testing, microstructural imaging, and in vitro biocompatibility assays help to determine how closely a construct can approach the performance of the native tissue. Bringing these elements together may support the gradual translation of fibre-based TM scaffolds into clinical practice. Full article
(This article belongs to the Section Biomaterials and Devices for Healthcare Applications)
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12 pages, 2937 KB  
Article
Preparation, Characterization and Biocompatibility of a Silk Fibroin/Bamboo Nanofibrillated Cellulose Composite Hydrogel
by Pan Wu, Chengli Wang, Di Wang, Jiahua Li and Wanfu Yue
Gels 2026, 12(1), 38; https://doi.org/10.3390/gels12010038 - 31 Dec 2025
Viewed by 741
Abstract
To address the limitations of pure silk fibroin (SF) hydrogels, such as poor mechanical strength and rapid degradation, a fully “green” composite hydrogel was developed by integrating bamboo nanofibrillated cellulose (BNC) with SF and crosslinked using the natural agent genipin. The composite formed [...] Read more.
To address the limitations of pure silk fibroin (SF) hydrogels, such as poor mechanical strength and rapid degradation, a fully “green” composite hydrogel was developed by integrating bamboo nanofibrillated cellulose (BNC) with SF and crosslinked using the natural agent genipin. The composite formed a stable interpenetrating network, as confirmed by means of SEM and FTIR. This structure led to significantly enhanced mechanical properties (increased storage modulus and pronounced shear-thinning behavior), moderate swelling, and a controllable degradation rate. In vitro biocompatibility assays demonstrated that the BNC-SF hydrogel was non-cytotoxic and excellently supported the adhesion, spreading, and proliferation of L929 fibroblasts. Notably, it exhibited a strong pro-migratory effect in a scratch assay. This work presents a high-performance, injectable scaffold material derived entirely from natural sources, showing great potential for tissue engineering and regenerative medicine applications. Full article
(This article belongs to the Section Gel Analysis and Characterization)
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49 pages, 5540 KB  
Review
Recent Advances in Silk Fibroin Derived from Bombyx mori for Regenerative Medicine
by Yuhao Zhang and Iman Roohani
J. Funct. Biomater. 2026, 17(1), 12; https://doi.org/10.3390/jfb17010012 - 24 Dec 2025
Cited by 8 | Viewed by 3806
Abstract
Bombyx mori silk fibroin (BMSF) has developed from a textile fibre into a mature biomaterial with broad utility in regenerative medicine, owing to its unique hierarchical molecular structure. Its excellent biocompatibility, tuneable mechanical properties, optical property, and controllable biodegradability arise from its protein [...] Read more.
Bombyx mori silk fibroin (BMSF) has developed from a textile fibre into a mature biomaterial with broad utility in regenerative medicine, owing to its unique hierarchical molecular structure. Its excellent biocompatibility, tuneable mechanical properties, optical property, and controllable biodegradability arise from its protein conformation, which can be precisely regulated through processing and fabrication strategies. Recent advances in bioengineering have further expanded the capabilities of BMSF, enabling the development of biomaterials with engineered architectures, tailored microtopographies, and enhanced bioactivity. These technological developments have facilitated the design of scaffolds that more effectively guide tissue regeneration and enhance functional outcomes. Such constructs have demonstrated promising outcomes in the regeneration of bone, cartilage, vascular, neural, corneal, and skin tissues. This review summarises current progress while emphasising emerging trends that couple BMSF’s unique molecular features with immune-responsive design, instructive microarchitectures that guide cell behaviour, composite scaffold design, and functionalisation with bioactive molecules. BMSF has been positioned as a structurally adaptable and biologically instructive platform whose continued progression will depend on integrating advanced fabrication, mechanistic understanding, and translational standardisation. Full article
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36 pages, 1058 KB  
Systematic Review
Functionalization Strategies of Chitosan-Based Scaffolds with Growth Factors for Bone Regeneration: A Systematic Review
by Jan Kiryk, Mateusz Michalak, Zuzanna Majchrzak, Marzena Laszczyńska, Sylwia Kiryk, Sylwia Szotek, Hanna Gerber, Izabela Nawrot-Hadzik, Jacek Matys and Maciej Dobrzyński
Mar. Drugs 2025, 23(10), 396; https://doi.org/10.3390/md23100396 - 9 Oct 2025
Cited by 8 | Viewed by 2759
Abstract
Bioactive agents can stimulate osteogenesis, angiogenesis, and cell proliferation; therefore, their application in bone regeneration offers significant therapeutic potential. The aim of this systematic review was to evaluate strategies for applying chitosan-based scaffolds with growth factors in bone regeneration. A structured literature search [...] Read more.
Bioactive agents can stimulate osteogenesis, angiogenesis, and cell proliferation; therefore, their application in bone regeneration offers significant therapeutic potential. The aim of this systematic review was to evaluate strategies for applying chitosan-based scaffolds with growth factors in bone regeneration. A structured literature search was conducted in July 2025 across the PubMed, Scopus, and Web of Science databases. Search terms included combinations of (chitosan scaffold) AND (growth factor OR BMP-2 OR VEGF OR FGF OR TGF-beta OR periostin OR PDGF OR IGF-1 OR EGF OR ANG-1 OR ANG-2 OR GDF-5 OR SDF-1 OR osteopontin). The study selection process followed PRISMA 2020 guidelines and the PICO framework. Out of 367 records, 226 were screened, and 17 studies met the eligibility criteria for qualitative analysis. BMP-2 was the most frequently investigated growth factor, studied in both in vitro and in vivo models, with rats and rabbits as the most common animal models. Scaffold compositions varied, incorporating hydroxyapatite, heparin, polyethylene glycol diacrylate, octacalcium phosphate-mineralized graphene, silk fibroin, and aloe vera. Growth factors were introduced using diverse methods, including microspheres, chemical grafting, covalent coupling, protein carriers, and nanohydroxyapatite mesopores. Most studies reported enhanced bone regeneration, although differences in models, scaffold composition, and delivery methods preclude definitive conclusions. The addition of growth factors generally improved osteoblast proliferation, angiogenesis, bone density, and expression of osteogenic markers (RunX2, COL1, OPN, OCN). Combining two bioactive agents further amplified osteoinduction and vascularization. Sustained-release systems, particularly those using heparin or hydroxyapatite, prolonged biological activity and improved regenerative outcomes. In conclusion, functionalization of chitosan-based scaffolds with growth factors shows promising potential for bone regeneration. Controlled-release systems and combinations of different bioactive molecules may offer synergistic effects on osteogenesis and angiogenesis. Further research should focus on optimizing scaffold compositions and delivery methods to tailor bioactive agent release for specific clinical applications. Full article
(This article belongs to the Section Biomaterials of Marine Origin)
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30 pages, 2013 KB  
Review
Biopolymers in Biotechnology and Tissue Engineering: A Comprehensive Review
by Maciej Grabowski, Dominika Gmyrek, Maria Żurawska and Anna Trusek
Macromol 2025, 5(3), 34; https://doi.org/10.3390/macromol5030034 - 21 Jul 2025
Cited by 12 | Viewed by 5655
Abstract
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 [...] Read more.
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
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20 pages, 2965 KB  
Article
Bioactive Hydrogel Scaffolds Integrating Chitosan, Silk Fibroin, and Aloe vera Extract for Enhanced Cartilage Tissue Regeneration
by Witwisitpong Maneechan, Phassorn Khumfu, Pensri Charoensit, Areeya Tuanchai, Sukunya Ross, Gareth M. Ross, Jatuporn Ngoenkam and Jarupa Viyoch
Polymers 2025, 17(10), 1409; https://doi.org/10.3390/polym17101409 - 20 May 2025
Cited by 13 | Viewed by 3395
Abstract
This study developed composite hydrogel scaffolds from chitosan (CS), silk fibroin (SF), and Aloe vera (AV) gel extract for cartilage tissue engineering. SF extracted from Nang-Laai silkworm cocoons showed high protein content (86.8%), while AV extract contained characteristic polysaccharides. Scaffolds with varying CS/SF/AV [...] Read more.
This study developed composite hydrogel scaffolds from chitosan (CS), silk fibroin (SF), and Aloe vera (AV) gel extract for cartilage tissue engineering. SF extracted from Nang-Laai silkworm cocoons showed high protein content (86.8%), while AV extract contained characteristic polysaccharides. Scaffolds with varying CS/SF/AV ratios were fabricated and evaluated for physicochemical and biological properties. Among all formulations, CS40/SF/AV (3.00%wt CS, 2.70%wt SF, 0.075%wt AV) exhibited superior porosity (72.23 ± 4.85%), pore size (79.57 ± 3.68 μm), and compressive strength, both in dry (6.67 ± 1.44 MPa) and wet states. It also showed controlled swelling (270%) and a stable degradation profile (55–57% over 21 days). FTIR and XRD confirmed successful component integration and semi-crystalline structure. In vitro, CS40/SF/AV supported chondrocyte adhesion, proliferation, and morphology retention over 28 days. Fluorescence imaging showed uniform cell distribution across the scaffold. These results highlight the CS40/SF/AV scaffold as a promising, biocompatible platform with optimal mechanical and structural properties for cartilage regeneration, offering potential for further in vivo applications. Full article
(This article belongs to the Special Issue Biomedical Applications of Intelligent Hydrogel 2nd Edition)
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13 pages, 484 KB  
Review
Recent Advances in Silk Fibroin-Based Composites for Bone Repair Applications: A Review
by Siyu Zhu, Qian Zhang, Xiang Xu, Zulan Liu, Guotao Cheng, Dingpei Long, Lan Cheng and Fangyin Dai
Polymers 2025, 17(6), 772; https://doi.org/10.3390/polym17060772 - 14 Mar 2025
Cited by 30 | Viewed by 5824
Abstract
Silk fibroin (SF), a natural high-molecular-weight fiber protein extracted from silk, has demonstrated immense potential in bone tissue repair and regeneration due to its exceptional physicochemical properties. Silk fibroin can be processed into various scaffold forms using diverse fabrication techniques, combined with other [...] Read more.
Silk fibroin (SF), a natural high-molecular-weight fiber protein extracted from silk, has demonstrated immense potential in bone tissue repair and regeneration due to its exceptional physicochemical properties. Silk fibroin can be processed into various scaffold forms using diverse fabrication techniques, combined with other biomaterials to create composite structures, or chemically modified to address a wide range of bone defect conditions. This review provides a comprehensive examination of the role of silk fibroin and its composites in bone tissue engineering, with particular emphasis on preclinical studies investigating various silk fibroin-based composite scaffolds in osteogenesis. Additionally, it discusses the current status and challenges in preparing silk fibroin scaffolds tailored to bone tissue defects and explores innovative approaches such as silk fibroin membranes, hydrogels, and 3D-printed constructs. The review begins with an introduction to bone biology, including its composition, structure, healing mechanisms, and the development of bone repair materials. It then delves into the unique properties of silk fibroin, including its composition, structure, and physicochemical attributes, which make it an ideal candidate for bone tissue engineering. This review provides valuable insights into their design, fabrication, and application by critically analyzing recent advancements in silk fibroin-based scaffolds and their functional modifications. Finally, it offers a forward-looking perspective on the future development and translational potential of silk fibroin and its composites in the field of bone repair materials. Full article
(This article belongs to the Special Issue Biomaterials Modification, Characterization and Applications)
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