骨组织工程支架用多孔镁合金的制备及其生物降解与骨响应机理

In order to solve the deficiency of strength, plasticity and forming ability for currently clinical used bone tissue engineering scaffolds made by bio-ceramic and polymer materials, the present project proposal proposes the research and development of Mg-based bone tissue engineering scaffold based on the merits of osteoinductivity and biodegradability of the magnesium alloy. Using titanium particles as pore media, the composite of Mg alloy/Ti particles will be produced by vacuum differential infiltration casting process. The detach problem of Ti particles filler and Mg alloy matrix will be solved according to the principle that pure titanium is corroded easily in hydrofluoric acid and magnesium alloy in hydrofluoric acid is very easy to form MgF2 compact protective film to protect the Mg matrix from corrosion. The infiltration casting process of magnesium alloy porous materials will be optimized by numerical simulation. The correlations between the pore structure characteristics of magnesium alloy scaffolds and mechanical properties, degradation behavior and cell adhesion and proliferation behavior will be studied systematically and established, and it will direct to prepare Mg-based bone tissue engineering scaffolds with the ideal configuration. The Mg-based porous scaffold will be performed the surface treatment by a chemical conversion coating method in order to further regulate the degradation behavior, and the regulation mechanism of degradation will be studied and clarified. The interaction between bone cells and Mg alloy scaffolds will be studied and the bone conduction and osteoinductivity (i.e. bone response) mechanism of Mg alloy tissue engineering scaffolds will be elucidated. The research output from the present project will lay a solid scientific theory and technical basis for further clinical applications research of Mg-based tissue engineering scaffolds.

针对临床应用的生物陶瓷和高分子材料制备的骨组织工程支架在强度、塑性和成形性等方面的不足，本申请提出利用镁合金表现出的成骨诱导和可降解特性，将镁合金制备成骨缺损修复用组织工程支架。以金属钛粒子为造孔介质，采用真空调压渗流铸造工艺制备镁合金/钛颗粒复合体，巧妙利用纯钛不耐氢氟酸腐蚀，而镁合金在氢氟酸中极易形成致密的MgF2保护膜而不被腐蚀的原理，解决填料粒子和镁合金基体的分离难题。采用数值模拟优化镁合金多孔材料渗流铸造制备工艺，研究镁合金组织工程支架的孔结构与其力学性能、降解行为及细胞黏附和增殖行为之间的关联规律，获得理想的骨组织工程支架构型。采用化学转化涂层法对镁合金组织工程支架进行表面处理，进一步调控组织工程支架的降解行为，阐明调控机理。研究细胞与组织工程支架的相互作用，揭示镁合金组织工程支架的骨传导和骨诱导(骨响应)机理。为镁合金骨组织工程支架的临床应用研究奠定坚实的科学理论和技术基础。

创伤、肿瘤切除、感染以及先天性骨病等常见病例都会涉及大段骨缺损的修复治疗，国内平均每年此类损伤功能丧失率可达19.8%，截肢率高达10.4%，严重威胁着患者的生命健康。骨组织工程支架可以从结构和功能上模拟待修复宿主组织，为组织再生重建提供三维再生空间。如何通过支架的孔隙特征（单元孔形结构，孔径分布和孔隙率等）设计来提高宿主细胞及组织长入速率、血管网络快速形成能力，进一步缩短再生修复周期，是目前节段性骨缺损修复支架研制的关键问题。本项目采用自主研发的专利制备技术，所研制的三维联通、孔隙特征可精确调控的可降解镁合金骨组织工程支架，可以免除负载骨细胞生长因子同样达到快速修复骨缺损的目的，这为实现快速高质量长入新骨、防止骨不连的发生提供了新的思路和更高效成骨的技术手段，具有光明的临床应用前景。