软骨缺乏自修复能力,其损伤会累及软骨下骨。骨软骨一体化修复是亟待解决的世界性难题。临床使用的微骨折、自体和异体骨软骨移植等方法存在修复填充不完整、来源有限、排异反应、纤维软骨等问题。目前,利用组织工程技术是国际研究热点。理想植入物应能同时提供适宜软骨和软骨下骨的力学强度和微环境,与解剖部位形态吻合,可控降解且能实现软骨与骨界面一体化及并发性再生重建。由于具优异生物安全性、力学性能、可降解性及促成骨、软骨活性,以镁合金为基体构建仿生双相支架显示出可行性和潜在优越性。
项目的研究目标是基于我国在医用镁合金领域扎实的前期研究基础和国际上的比较优势,通过“材料与结构设计创新、制备工艺创新以及内源性促再生机理创新”,研发 3D 打印镁合金多孔支架复合水凝胶/陶瓷双相活性界面,构建用于骨软骨修复的“结构-功能”一体化仿生全降解支架,通过体内外实验研究验证其安全性、有效性和优越性,并阐明支架降解与组织重建的匹配关系以及内源性诱导组织再生的关键理化因素及机制。
围绕上述目标,项目主要设置三方面研究内容:1) 3D 打印镁合金多孔支架基体的设计制备; 2) 镁合金支架上复合仿生双相活性界面研究; 3) 镁合金复合双相支架体内外促骨软骨再生及机制研究。拟解决的关键技术问题:支架“力学性能和结构可控的镁合金支架基体的 3D打印制备支架的可控降解和生物相容性”、“仿生软骨和软骨下骨结构的双相界面生物学功能适配”。拟解决的重要科学问题:阐明支架孔结构、镁降解产物、双相仿生界面等关键理化因素诱导软骨和骨再生的细胞和分子学机制。
Articular cartilage lacks self-repair capabilities, and its injuries can affect the subchondral bone. The integrated repair of bone and cartilage is an urgent global challenge that needs to be addressed. Clinical methods such as microfracture, autologous and allogeneic osteochondral transplantation have issues including incomplete filling, limited sources, immune rejection, and the formation of fibrocartilage. Currently, the use of tissue engineering technology is a hot topic in international research. An ideal implant should provide both the mechanical strength and microenvironment suitable for cartilage and subchondral bone, match the anatomical site morphology, be controllable in degradation, and achieve integrated reconstruction of the cartilage-bone interface and concurrent regeneration. Due to its excellent biosecurity, mechanical properties, degradability, and the ability to promote osteogenic and chondrogenic activity, the construction of a biomimetic biphasic scaffold with a magnesium alloy as the matrix has shown feasibility and potential superiority.
The research objective of the project is to leverage China's solid preliminary research foundation in the field of biomedical magnesium alloys and its comparative advantages internationally. Through "innovation in material and structural design, preparation process, and endogenous regeneration mechanism," the project aims to develop a 3D printed magnesium alloy porous scaffold with a hydrogel/ceramic biphasic active interface. This will construct a "structure-function" integrated biomimetic fully degradable scaffold for osteochondral repair. The safety, effectiveness, and superiority will be verified through in vitro and in vivo experiments, and the matching relationship between scaffold degradation and tissue reconstruction, as well as the key physicochemical factors and mechanisms of endogenous induction of tissue regeneration, will be elucidated.
To achieve the above objectives, the project mainly sets three research contents: 1) The design and preparation of the 3D printed magnesium alloy porous scaffold matrix; 2) The study of the biomimetic biphasic active interface on the magnesium alloy scaffold; 3) The study of the promotion of osteochondral regeneration and mechanisms of the magnesium alloy composite biphasic scaffold in vitro and in vivo. The key technical issues to be solved include: "The 3D printing preparation of the scaffold with controllable mechanical properties and structure, the controllable degradation and biocompatibility of the magnesium alloy scaffold matrix," and "The biological function adaptation of the biphasic interface that mimics the structure of cartilage and subchondral bone." The important scientific issues to be addressed are: to elucidate the cellular and molecular mechanisms by which key physicochemical factors such as scaffold pore structure, magnesium degradation products, and biphasic biomimetic interface induce cartilage and bone regeneration.