丝素蛋白在骨组织工程中的应用
Application of Silk Fibroin in Bone Tissue Engineering
DOI: 10.12677/hjbm.2025.154083, PDF,    科研立项经费支持
作者: 龚砚硕, 付 钢*：口腔疾病研究重庆市重点实验室，重庆；重庆医科大学附属口腔医院修复科，重庆
关键词: 丝素蛋白；骨缺损；骨组织工程；Silk Fibroin； Bone Defect； Bone Tissue Engineering
摘要: 骨缺损的修复仍是临床实践中的一大挑战，许多因素限制了自体和同种异体骨的应用。骨组织工程利用支架、细胞和生物活性因子的特殊混合，形成三维模拟骨结构，修复骨缺损，再生骨组织。丝素蛋白作为一种天然生物材料，凭借良好的生物相容性、可控的生物降解性、低免疫原性，以及广泛的来源和易于加工等特征，被设计成膜、水凝胶和支架等结构，在骨组织工程领域发挥着重要作用，拥有广阔的应用前景。本文叙述了丝素蛋白的结构属性和丝素蛋白溶液的制备流程，并对丝素蛋白在骨组织工程中各种形式的应用和改进方法进行了叙述总结。此外，本文还展望了丝素蛋白现阶段在骨组织工程中存在的瓶颈以及接下来的改进方向，展望了更为广阔的前景。
Abstract: The repair of large bone defects remains a major challenge in clinical practice, and many factors limit the application of autologous and allogeneic bone. Bone tissue engineering uses a special mixture of scaffolds, cells and bioactive factors to form a three-dimensional simulated bone structure, repair bone defects, and regenerate bone tissue. Silk fibroin, as a natural biomaterial, has good biocompatibility, controlled biodegradability, low immunogenicity, wide sources and easy processing. Silk fibroin has been designed into membranes, hydrogels and scaffolds, and plays an important role in bone tissue engineering with broad application prospects. In this paper, the structural properties of silk fibroin and the preparation process of silk fibroin solution are described, and the application and improvement methods of silk fibroin in bone tissue engineering are summarized. In addition, we also prospected the bottleneck of silk fibroin in bone tissue engineering at the present stage and the future improvement direction, and looked forward to a broader prospect.
文章引用：龚砚硕, 付钢. 丝素蛋白在骨组织工程中的应用[J]. 生物医学, 2025, 15(4): 773-779. https://doi.org/10.12677/hjbm.2025.154083

参考文献

[1] Chen, J., Xing, X., Liu, D., Gao, L., Liu, Y., Wang, Y., et al. (2024) Copper Nanoparticles Incorporated Visible Light-Curing Chitosan-Based Hydrogel Membrane for Enhancement of Bone Repair. Journal of the Mechanical Behavior of Biomedical Materials, 158, Article ID: 106674. [Google Scholar] [CrossRef] [PubMed]
[2] Li, L., Zhou, G., Wang, Y., Yang, G., Ding, S. and Zhou, S. (2015) Controlled Dual Delivery of BMP-2 and Dexamethasone by Nanoparticle-Embedded Electrospun Nanofibers for the Efficient Repair of Critical-Sized Rat Calvarial Defect. Biomaterials, 37, 218-229. [Google Scholar] [CrossRef] [PubMed]
[3] Li, M., You, J., Qin, Q., Liu, M., Yang, Y., Jia, K., et al. (2023) A Comprehensive Review on Silk Fibroin as a Persuasive Biomaterial for Bone Tissue Engineering. International Journal of Molecular Sciences, 24, Article 2660. [Google Scholar] [CrossRef] [PubMed]
[4] Mao, Z., Bi, X., Yu, C., Chen, L., Shen, J., Huang, Y., et al. (2024) Mechanically Robust and Personalized Silk Fibroin-Magnesium Composite Scaffolds with Water-Responsive Shape-Memory for Irregular Bone Regeneration. Nature Communications, 15, Article No. 4160. [Google Scholar] [CrossRef] [PubMed]
[5] Sahoo, J.K., Hasturk, O., Falcucci, T. and Kaplan, D.L. (2023) Silk Chemistry and Biomedical Material Designs. Nature Reviews Chemistry, 7, 302-318. [Google Scholar] [CrossRef] [PubMed]
[6] Wu, H., Lin, K., Zhao, C. and Wang, X. (2022) Silk Fibroin Scaffolds: A Promising Candidate for Bone Regeneration. Frontiers in Bioengineering and Biotechnology, 10, Article 1054379. [Google Scholar] [CrossRef] [PubMed]
[7] Zhang, M., Matinlinna, J.P., Tsoi, J.K.H., Liu, W., Cui, X., Lu, W.W., et al. (2020) Recent Developments in Biomaterials for Long-Bone Segmental Defect Reconstruction: A Narrative Overview. Journal of Orthopaedic Translation, 22, 26-33. [Google Scholar] [CrossRef] [PubMed]
[8] Wang, H., Zhang, Y., Zhang, M. and Zhang, Y. (2024) Functional Modification of Silk Fibroin from Silkworms and Its Application to Medical Biomaterials: A Review. International Journal of Biological Macromolecules, 259, Article ID: 129099. [Google Scholar] [CrossRef] [PubMed]
[9] Zhou, C., Confalonieri, F., Jacquet, M., Perasso, R., Li, Z. and Janin, J. (2001) Silk Fibroin: Structural Implications of a Remarkable Amino Acid Sequence. Proteins: Structure, Function, and Bioinformatics, 44, 119-122. [Google Scholar] [CrossRef] [PubMed]
[10] Aramwit, P., Kanokpanont, S., De-Eknamkul, W. and Srichana, T. (2009) Monitoring of Inflammatory Mediators Induced by Silk Sericin. Journal of Bioscience and Bioengineering, 107, 556-561. [Google Scholar] [CrossRef] [PubMed]
[11] Deshpande, P.B., Kumar, G.A., Kumar, A.R., Shavi, G.V., Karthik, A., Reddy, M.S., et al. (2011) Supercritical Fluid Technology: Concepts and Pharmaceutical Applications. PDA Journal of Pharmaceutical Science and Technology, 65, 333-344. [Google Scholar] [CrossRef] [PubMed]
[12] Kim, H.J., Kim, M.K., Lee, K.H., Nho, S.K., Han, M.S. and Um, I.C. (2017) Effect of Degumming Methods on Structural Characteristics and Properties of Regenerated Silk. International Journal of Biological Macromolecules, 104, 294-302. [Google Scholar] [CrossRef] [PubMed]
[13] Nguyen, T.P., Nguyen, Q.V., Nguyen, V., Le, T., Huynh, V.Q.N., Vo, D.N., et al. (2019) Silk Fibroin-Based Biomaterials for Biomedical Applications: A Review. Polymers, 11, Article 1933. [Google Scholar] [CrossRef] [PubMed]
[14] Quan, S., Yang, J., Huang, S., Shao, J., Liu, Y. and Yang, H. (2025) Silk Fibroin as a Potential Candidate for Bone Tissue Engineering Applications. Biomaterials Science, 13, 364-378. [Google Scholar] [CrossRef] [PubMed]
[15] Rockwood, D.N., Preda, R.C., Yücel, T., Wang, X., Lovett, M.L. and Kaplan, D.L. (2011) Materials Fabrication from Bombyx Mori Silk Fibroin. Nature Protocols, 6, 1612-1631. [Google Scholar] [CrossRef] [PubMed]
[16] Sun, W., Gregory, D.A., Tomeh, M.A. and Zhao, X. (2021) Silk Fibroin as a Functional Biomaterial for Tissue Engineering. International Journal of Molecular Sciences, 22, Article 1499. [Google Scholar] [CrossRef] [PubMed]
[17] Wang, H., Zhang, Y. and Wei, Z. (2021) Dissolution and Processing of Silk Fibroin for Materials Science. Critical Reviews in Biotechnology, 41, 406-424. [Google Scholar] [CrossRef] [PubMed]
[18] Wang, S., Li, X., Xu, W., Yu, Q. and Fang, S. (2024) Advances of Regenerated and Functionalized Silk Biomaterials and Application in Skin Wound Healing. International Journal of Biological Macromolecules, 254, Article ID: 128024. [Google Scholar] [CrossRef] [PubMed]
[19] Wei, S., Wang, Y., Sun, Y., Gong, L., Dai, X., Meng, H., et al. (2023) Biodegradable Silk Fibroin Scaffold Doped with Mineralized Collagen Induces Bone Regeneration in Rat Cranial Defects. International Journal of Biological Macromolecules, 235, Article ID: 123861. [Google Scholar] [CrossRef] [PubMed]
[20] Wang, Y., Yang, Z., Chen, X., Jiang, X. and Fu, G. (2023) Silk Fibroin Hydrogel Membranes Prepared by a Sequential Cross-Linking Strategy for Guided Bone Regeneration. Journal of the Mechanical Behavior of Biomedical Materials, 147, Article ID: 106133. [Google Scholar] [CrossRef] [PubMed]
[21] Del Bianco, L., Spizzo, F., Yang, Y., Greco, G., Gatto, M.L., Barucca, G., et al. (2022) Silk Fibroin Films with Embedded Magnetic Nanoparticles: Evaluation of the Magneto-Mechanical Stimulation Effect on Osteogenic Differentiation of Stem Cells. Nanoscale, 14, 14558-14574. [Google Scholar] [CrossRef] [PubMed]
[22] Wang, C., Fang, H., Qi, X., Hang, C., Sun, Y., Peng, Z., et al. (2019) Silk Fibroin Film-Coated Mgznca Alloy with Enhanced in Vitro and in Vivo Performance Prepared Using Surface Activation. Acta Biomaterialia, 91, 99-111. [Google Scholar] [CrossRef] [PubMed]
[23] Xiao, M., Yao, J., Shao, Z. and Chen, X. (2024) Silk-Based 3D Porous Scaffolds for Tissue Engineering. ACS Biomaterials Science & Engineering, 10, 2827-2840. [Google Scholar] [CrossRef] [PubMed]
[24] Liu, F., Liu, C., Zheng, B., He, J., Liu, J., Chen, C., et al. (2020) Synergistic Effects on Incorporation of β-Tricalcium Phosphate and Graphene Oxide Nanoparticles to Silk Fibroin/Soy Protein Isolate Scaffolds for Bone Tissue Engineering. Polymers, 12, Article 69. [Google Scholar] [CrossRef] [PubMed]
[25] Panahifar, A., Chapman, L.D., Weber, L., Samadi, N. and Cooper, D.M.L. (2018) Biodistribution of Strontium and Barium in the Developing and Mature Skeleton of Rats. Journal of Bone and Mineral Metabolism, 37, 385-398. [Google Scholar] [CrossRef] [PubMed]
[26] Zhao, Q., Ni, Y., Wei, H., Duan, Y., Chen, J., Xiao, Q., et al. (2023) Ion Incorporation into Bone Grafting Materials. Periodontology 2000, 94, 213-230. [Google Scholar] [CrossRef] [PubMed]
[27] Zhang, J., Tang, L., Qi, H., Zhao, Q., Liu, Y. and Zhang, Y. (2019) Dual Function of Magnesium in Bone Biomineralization. Advanced Healthcare Materials, 8, e1901030. [Google Scholar] [CrossRef] [PubMed]
[28] Li, Z., Peng, S., Pan, H., Tang, B., Lam, R.W.M. and Lu, W.W. (2011) Microarchitecture and Nanomechanical Properties of Trabecular Bone after Strontium Administration in Osteoporotic Goats. Biological Trace Element Research, 145, 39-46. [Google Scholar] [CrossRef] [PubMed]
[29] Wu, Y., Adeeb, S.M., Duke, M.J., Munoz-Paniagua, D. and Doschak, M.R. (2013) Compositional and Material Properties of Rat Bone after Bisphosphonate And/or Strontium Ranelate Drug Treatment. Journal of Pharmacy & Pharmaceutical Sciences, 16, 52-64. [Google Scholar] [CrossRef] [PubMed]
[30] Wu, T., Liu, W., Huang, S., Chen, J., He, F., Wang, H., et al. (2021) Bioactive Strontium Ions/Ginsenoside Rg1-Incorporated Biodegradable Silk Fibroin-Gelatin Scaffold Promoted Challenging Osteoporotic Bone Regeneration. Materials Today Bio, 12, Article ID: 100141. [Google Scholar] [CrossRef] [PubMed]
[31] Shaygani, H., Shamloo, A., Akbarnataj, K. and Maleki, S. (2024) In Vitro and in Vivo Investigation of Chitosan/Silk Fibroin Injectable Interpenetrating Network Hydrogel with Microspheres for Cartilage Regeneration. International Journal of Biological Macromolecules, 270, Article ID: 132126. [Google Scholar] [CrossRef] [PubMed]
[32] Yu, M., Huang, R., Hua, J., Ru, M., You, R., Huang, Y., et al. (2024) High Biocompatible Bone Screw Enabled by a Rapid and Robust Chitosan/Silk Fibroin Composite Material. International Journal of Biological Macromolecules, 267, Article ID: 131519. [Google Scholar] [CrossRef] [PubMed]
[33] Liu, Y., Shi, C., Ming, P., Yuan, L., Jiang, X., Jiang, M., et al. (2024) Biomimetic Fabrication of SR-Silk Fibroin Co-Assembly Hydroxyapatite Based Microspheres with Angiogenic and Osteogenic Properties for Bone Tissue Engineering. Materials Today Bio, 25, Article ID: 101011. [Google Scholar] [CrossRef] [PubMed]
[34] Zhou, L., Chen, D., Wu, R., Li, L., Shi, T., Shangguang, Z., et al. (2024) An Injectable and Photocurable Methacrylate-Silk Fibroin/Nano-Hydroxyapatite Hydrogel for Bone Regeneration through Osteoimmunomodulation. International Journal of Biological Macromolecules, 263, Article ID: 129925. [Google Scholar] [CrossRef] [PubMed]
[35] Salazar, V.S., Gamer, L.W. and Rosen, V. (2016) BMP Signalling in Skeletal Development, Disease and Repair. Nature Reviews Endocrinology, 12, 203-221. [Google Scholar] [CrossRef] [PubMed]
[36] Mao, Y., Zhang, Y., Wang, Y., Zhou, T., Ma, B. and Zhou, P. (2023) A Multifunctional Nanocomposite Hydrogel with Controllable Release Behavior Enhances Bone Regeneration. Regenerative Biomaterials, 10, rbad046. [Google Scholar] [CrossRef] [PubMed]
[37] Lv, Z., Hu, T., Bian, Y., Wang, G., Wu, Z., Li, H., et al. (2022) A MgFe‐LDH Nanosheet‐incorporated Smart Thermo‐responsive Hydrogel with Controllable Growth Factor Releasing Capability for Bone Regeneration. Advanced Materials, 35, e2206545. [Google Scholar] [CrossRef] [PubMed]
[38] Li, M., Wu, H., Gao, K., Wang, Y., Hu, J., Guo, Z., et al. (2024) Smart Implantable Hydrogel for Large Segmental Bone Regeneration. Advanced Healthcare Materials, 13, e2402916. [Google Scholar] [CrossRef] [PubMed]
[39] Paladini, F. and Pollini, M. (2022) Novel Approaches and Biomaterials for Bone Tissue Engineering: A Focus on Silk Fibroin. Materials, 15, Article 6952. [Google Scholar] [CrossRef] [PubMed]
[40] Tuwalska, A., Grabska-Zielińska, S. and Sionkowska, A. (2022) Chitosan/silk Fibroin Materials for Biomedical Applications—A Review. Polymers, 14, Article 1343. [Google Scholar] [CrossRef] [PubMed]

为你推荐