Application of Silk Fibroin Hydrogel in Bone Tissue Engineering

Authors

  • Zijin Wang

DOI:

https://doi.org/10.61173/7j8hbc88

Keywords:

Silk fibroin hydrogel, Bone tissue engineer-ing, Composite materials

Abstract

Silk fibroin (SF) hydrogel has emerged as a promising biomaterial for bone tissue engineering (BTE) due to its excellent biocompatibility, controllable degradation, and versatile processing capabilities. This review summarizes recent advancements in the application of SF hydrogel and its composites in BTE, focusing on its properties, preparation methods, and innovative modifications to enhance mechanical strength and biofunctionality. The shape of hydrogel improves the biocompatibility of SF material, making it better used in bone tissue engineering. SF hydrogel has demonstrated significant potential in addressing bone defects, osteoarthritis, periodontal regeneration, antibiotic delivery, and stem cell therapy. Composite materials, such as collagen, chitosan, and alginate, further expand its applications by improving mechanical and biological performance. The introduction of more composite materials further enhanced the application of SF hydrogel in bone tissue engineering. Despite these advancements, challenges remain, including the need for improved mechanical properties, reduced immune responses, and more extensive clinical validation. Future research should prioritize large-animal studies and clinical trials to facilitate the translation of SF hydrogel-based therapies into clinical practice.

References

protein, as it is a non autologous biomaterial. In addi- Mater Sci: Mater Med, 2014, 25: 2445–2461. tion, the mechanical properties of SF scaffolds are still [2] Yao X, Zou S, Fan S, Niu Q, Zhang Y. Bioinspired silk poor compared to traditional scaffold materials, and their fibroin materials: From silk building blocks extraction and practicality needs further systematic research and clinical reconstruction to advanced biomedical applications[J]. Materials

application verification. Speaking of which, a lot of work Today Bio, 2022, 16: 100381. needs to be done to further clarify the long-term safety of [3] Dickerson MB, Fillery SP, Koerner H, et al. Dielectric SF scaffolds, as the degradation products of SF biomate- breakdown strength of regenerated silk fibroin films as a function

rials may trigger the immune system. Therefore, although of protein conformation[J]. Biomacromolecules, 2013, 14(10): the bone regeneration ability of SF materials has been 3509–3514. demonstrated in small animal models, there is still a lack [4] Wang T, Li Y, Liu J, et al. Intraarticularly injectable silk of validation in large animal models. In addition, further hydrogel microspheres with enhanced mechanical and structural

research is needed on the osteogenic signaling pathway stability to attenuate osteoarthritis[J]. Biomaterials, 2022, 286: of SF. At present, products designed based on SF have 121611. not been widely applied in clinical practice, which may [5] Lee YJ, Lee JS, Ajiteru O, et al. Biocompatible fluorescent be due to a lack of data on the safety and efficacy of SF. silk fibroin bioink for digital light processing 3D printing[J]. Int

At present, there are only 7 SF based design products suc- J Biol Macromol, 2022, 213: 317–327. cessfully approved for medical devices in China, which [6] Peng W, Li D, Dai K, et al. Recent progress of collagen, are mainly used for skin dressings (4 cases) and abdomi- chitosan, alginate and other hydrogels in skin repair and wound

nal, vaginal and dental bone fillers (1 case each), of which dressing applications[J]. Int J Biol Macromol, 2022, 208: 400– 3 cases are SF hydrogels. In addition, currently only 3 SF 408. based product clinical trials have been completed globally, [7] Patel DK, Dutta SD, Hexiu J, et al. 3D-printable chitosan/silk and 5 clinical trials are in an undeveloped or unfinished fibroin/cellulose nanoparticle scaffolds for bone regeneration via

state [27]. The vast majority of related basic research M2 macrophage polarization[J]. Carbohydr Polym, 2022, 281: focuses on in vivo or in vitro evaluation of small animal 119077. models of SF. Therefore, we urgently need data from large [8] Liu J, Yang B, Li M, et al. Enhanced dual network hydrogels animal in vivo evaluation and randomized controlled hu- consisting of thiolated chitosan and silk fibroin for cartilage

man trials to promote the practical application of SF based tissue engineering[J]. Carbohydr Polym, 2019, 227: 115335.

hydrogels. [9] Birmingham, E., Niebur, G. L., & McHugh, P. E. (2012). Osteogenic differentiation of mesenchymal stem cells is regulated by osteocyte and osteoblast cells in a simplified bone 6. Conclusion niche. Silk fibroin hydrogel represents a highly versatile and [10] Klotz BJ, Gawlitta D, Rosenberg AJ, et al. Gelatineffective material for bone tissue engineering, offering Methacryloyl hydrogels: towards Biofabrication-Based tissue

unique advantages such as biocompatibility, tunable deg- repair[J]. Trends Biotechnol, 2016, 34(5): 394–407. radation, and the ability to mimic the extracellular matrix. [11] Luetchford KA, Chaudhuri JB, De Bank PA. Silk fibroin/ Recent innovations in composite materials and preparation gelatin microcarriers as scaffolds for bone tissue engineering[J].

techniques have significantly enhanced their mechanical Mater Sci Eng C, 2019, 106: 110116. Dean&Francis ISSN 2959-409X [12] Liu Q, Chen L, Liu H, et al. Promotion of bone defect eggshell-derived hydroxyapatite-incorporated fibroin-alginate repairs using multiscale 3D printed silk porous hydrogel composite hydrogel for bone tissue engineering[J]. Int J Biol

scaffolds[J]. Acta Biomater, 2025. Macromol, 2021, 193: 799–808. [13] Meng L, Shao C, Cui C, et al. Autonomous Self-Healing [21] Du J, Liu Y, Wu X, et al. BRD9-mediated chromatin Silk fibroin injectable hydrogels formed via Surfactant-Free remodeling suppresses osteoclastogenesis through negative

Hydrophobic Association[J]. ACS Appl Mater Interfaces, 2019, feedback mechanism[J]. Nat Commun, 2023, 14(1). 12(1): 1628–1639. [22] Lyu J, Shen S, Hao Y, et al. The impact of Thiopeptide [14] Wu X, Zhou M, Jiang F, et al. Marginal sealing around antibiotics on inflammatory responses in periodontal integral bilayer scaffolds for repairing osteochondral defects tissues through the regulation of the MAPK pathway[J]. Int

based on photocurable silk hydrogels[J]. Bioactive Materials, Immunopharmacol, 2024, 133: 112094. 2021, 6(11): 3976-3986. [23] Zhang P, Sun Y, Yang H, et al. Vancomycin-loaded silk [15] Wu X, Zhou M, Jiang F, et al. Marginal sealing around fibroin microspheres in an injectable hydrogel for chronic

integral bilayer scaffolds for repairing osteochondral defects osteomyelitis therapy[J]. Front Bioeng Biotechnol, 2023, 11.

based on photocurable silk hydrogels[J]. Bioact Mater, 2021, [24] Zhou W, Bai T, Wang L, et al. Biomimetic AgNPs@ 6(11): 3976–3986. antimicrobial peptide/silk fibroin coating for infection-trigger [16] Cheng Y, Cheng G, Xie C, et al. Biomimetic silk fibroin antibacterial capability and enhanced osseointegration[J]. Bioact

hydrogels strengthened by silica nanoparticles distributed Mater, 2022, 20: 64–80.

nanofibers facilitate bone repair[J]. Adv Healthc Mater, 2021, [25] Ribeiro M, Ferraz MP, Monteiro FJ, et al. Antibacterial 10(9). silk fibroin/nanohydroxyapatite hydrogels with silver and gold [17] Wang T, Li Y, Liu J, et al. Intraarticularly injectable silk nanoparticles for bone regeneration[J]. Nanomedicine, 2016, hydrogel microspheres with enhanced mechanical and structural 13(1): 231–239.

stability to attenuate osteoarthritis[J]. Biomaterials, 2022, 286: [26] Ou L, Lan Y, Feng Z, et al. Functionalization of SF/HAP 121611. Scaffold with GO-PEI-miRNA inhibitor Complexes to Enhance [18] Rui K, Tang X, Shen Z, et al. Exosome inspired photo- Bone Regeneration through Activating Transcription Factor 4[J].

triggered gelation hydrogel composite on modulating Theranostics, 2019, 9(15): 4525–4541. immune pathogenesis for treating rheumatoid arthritis[J]. J [27] ClinicalTrials.gov. Clinical trial database[EB/OL]. [n.d.].

Nanobiotechnol, 2023, 21(1). Available: https://www.clinicaltrials.gov/search?term=silk%20 [19] Wu S, Zhou X, Ai Y. Pro-angiogenic photo-crosslinked silk fibroin&limit=50&page=1 fibroin hydrogel: a potential candidate for repairing alveolar

bone defects[J]. J Appl Oral Sci, 2023, 31. [20] Chuysinuan P, Nooeaid P, Thanyacharoen T, et al. Injectable

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Published

2025-08-26