基于丝素蛋白材料构建骨组织修复支架的三维多孔结构体系的研究进展

Research progress on the construction of three-dimensional porous structure of bone tissue repair scaffolds based on silk fibroin materials

随医学技术和认知水平的提高,骨组织缺损的治疗理念逐渐从组织移植向组织再生模式转变。三维(3D)多孔支架在骨组织工程研究中起着关键性的作用,是种子细胞在形成组织之前赖以生存的生物学载体,能为组织再生提供空间场所。本文针对基于丝素蛋白(SF)生物材料构建3D多孔支架的研究进展进行了总结和讨论。首先,概述了自然骨组织的多层次多孔结构特征;其次,总结了SF材料的组成和结构特征,及其卓越的生物相容性、力学性能和生物可降解性能等特性;随后,着重讨论了SF基3D骨组织修复多孔支架典型的制备技术,包括冷冻干燥法、粒子沥滤法、生物3D打印法、复合制造技术对3D支架多孔结构的控制能力,以及多孔结构对细胞生长行为和骨组织再生的影响;最后,对SF构建的骨组织修复支架所面临的挑战和发展前景进行了展望,强调了合成生物技术为解决SF基多孔支架应用于骨组织工程领域所存在的问题提供了有力的工具。

Bone defects caused by trauma, tumors or congenital diseases seriously affect the physical and mental health of human beings. Autologous bone and allogeneic bone transplantation are the gold standard in clinical treatment, but they have certain limitations due to their limited sources, risks of immune response and infection. In recent years, with the improvement of medical technology and cognitive level, the treatment concept of bone tissue defect has gradually changed from tissue transplantation to tissue regeneration mode. Three-dimensional(3D) porous scaffolds play a key role in bone tissue engineering research, serving as biological carriers for seed cells to survive before forming tissues, providing a space for tissue regeneration. The ideal bone tissue scaffold should have good biocompatibility, a porous structure which is conducive to the growth and differentiation of bone cells, suitable mechanical properties, and matching degradation properties. Successful 3D scaffold material design requires understanding the composition and structure of natural bone tissue, selecting appropriate biomaterials, and controllably constructing 3D porous structures at multi-scales through certain fabrication techniques. Natural bone tissue is a composite material with a hierarchical porous structure, which is composed of dense cortical bone in the outer layer and porous cancellous bone in the inner layer. From the perspective of bionics, the regulation of porous scaffolds at multiple scales is an important link in mimicking the hierarchical structure of bone tissue. Silk fibroin(SF), as a natural protein material with good biocompatibility and biodegradability, excellent mechanical properties and easy processing,has become an excellent candidate for the construction of 3D porous scaffolds. This paper summarizes and discusses the research progress of the construction of 3D porous scaffolds based on SF biomaterials. First of all, the characteristics of the multi-layered porous structure of natural bone tissue are summarized;secondly, the composition and structural characteristics of SF materials, as well as their excellent biocompatibility, mechanical properties and biodegradability are described;subsequently, the typical fabrication techniques of SF-based 3D porous scaffolds for bone tissue repair are introduced, including freeze-drying, particle leaching, 3D bioprinting, and composite manufacturing technology, and their ability to control the porous structure of 3D scaffolds, the effects of porous structure on cell growth behavior and bone tissue regeneration are also discussed;finally, the design and fabrication challenges and development prospects of SF-constructed bone tissue repair scaffolds are prosposed, emphasizing that synthetic biology could provide a powerful tool for solving the problems existing in the application of SF-based porous scaffolds in the field of bone tissue engineering.