基于胶原自组装/矿化协同策略制备掺锶矿化胶原支架修复骨缺损

The excellent mechanical and biological functions of mineralized collagen fibers are closely related to the intrafibrillar mineralization of collagen fibers. At present, in vitro intrafibrillar mineralization of collagen mainly rely on amorphous calcium phosphate(ACP) nanoparticles stabilized by non-collagenous proteins(NCPs) analogues, and enter the collagen fibers for intrafibrillar mineralization following collagen self-assembly(MFS). However, the MFS mineralization model fails to fully explain the mechanism of mineralization of collagen fibers in vivo and is not suitable for the incorporation of trace elements into collagen scaffolds. In this project, by summarizing the current mechanisms of intrafibrillar mineralization of collagen and self-assembly mechanism of collagen, it is proposed to use amphoteric polycarboxylate carboxymethyl chitosan (CMC) as a biomimetic analogue of NCPs to stabilize ACP(pH<isoelectric point) under acidic conditions to perform synchronous self-assembly/mineralization of collagen(SSM). In addition, strontium will be incorporated into the mineralized collagen scaffold with SSM mode, which makes it more capable of promoting osteogenesis and inhabiting osteoclastogenesis and regulating immune microenvironment. By studying the SSM model, we can further elucidate the rules of biomineralization in vivo and obtain a new biomimetic mineralization strategy that incorporates trace elements into mineralized collagen scaffolds, so as to solve bone defects or insufficiency of bone in the clinical practices of oral and maxillofacial surgery and implantology.

矿化胶原纤维优异的力学和生物学功能与胶原纤维内矿化密不可分。目前，体外胶原纤维内矿化主要靠非胶原蛋白(NCPs)类似物稳定的无定形磷酸钙(ACP)纳米颗粒在胶原完成自组装后进入胶原纤维内部实现纤维内矿化(MFS)。但是，MFS矿化模型未能完全解释体内胶原纤维内矿化的机制，也不适于将微量元素掺入胶原支架。本课题通过对现有胶原纤维内矿化和胶原自组装机制的梳理，提出使用两性聚电解质羧甲基壳聚糖(CMC)作为NCPs仿生类似物在酸性条件下稳定ACP(pH<等电点)，进行胶原自组装和ACP纳米颗粒进入胶原纤维内部协同完成的矿化模式(SSM)。同时将锶以SSM模式掺入矿化胶原支架，从而使其具有更强的促进成骨抑制破骨和调节免疫微环境能力。通过研究SSM模式，可以进一步阐明体内生物矿化的规律并获得将微量元素掺入矿化胶原支架的新仿生矿化策略，用于解决口腔颌面外科临床面对的骨缺损或种植骨量不足等问题。

矿化胶原纤维优异的力学和生物学功能与胶原纤维内矿化密不可分。目前，体外胶原纤维内矿化主要靠非胶原蛋白(NCPs)类似物稳定的无定形磷酸钙(ACP)纳米颗粒在胶原完成自组装后进入胶原纤维内部实现纤维内矿化(MFS)。但是，MFS矿化模型未能完全解释体内胶原纤维内矿化的机制，也不适于将微量元素掺入胶原支架。本课题通过对现有胶原纤维内矿化和胶原自组装机制的梳理，提出使用两性聚电解质羧甲基壳聚糖(CMC)作为NCPs仿生类似物在酸性条件下稳定ACP(pH<等电点)，进行胶原自组装和ACP纳米颗粒进入胶原纤维内部协同完成的矿化模式(SSM)。同时将锶以SSM模式掺入矿化胶原支架，从而使其具有更强的促进成骨抑制破骨和调节免疫微环境能力。通过研究SSM模式，可以进一步阐明体内生物矿化的规律并获得将微量元素掺入矿化胶原支架的新仿生矿化策略，用于解决口腔颌面外科临床面对的骨缺损或种植骨量不足等问题。