新型可注射骨组织工程仿生矿化复合支架材料的研究

Two great challenges for bone reconstruction by composite scaffold still existed in clinical application: one was that the anchoring strength between organic and inorganic materials was weak; another was difficult to form synostosis between implanted materials and autogenous bone after implantation. Based on our previous research about stimulating angiogenesis of strontium-doped calcium polyphosphate (SCPP) scaffold and universal adhesive and inducing biomineralization of dopamine, a new idea that using injectable bone tissue and biomimetic mineralized scaffolds was raised. In our system, SCPP was employed as inorganic constituent, meanwhile, the reverse temperature sensitive material-dopamine polymer derivatives prepared by L-lactide-polyethylene glycol-L-lactide（PLGA-PEO-PLGA）was selected as organic constituent. The feasibility of promoting interface bonding between organic and inorganic phase in composite process was explored. This scaffold was injected to bone defects and then hydrogel formed. Moreover, at earlier stage of implantation, biomimetic mineralization might form synostosis between scaffold and autogenous bone. In a word, the aim of this topic was to investigate the structure and performance of this novel scaffold and therefore supply a potential composite scaffold for clinical application. It also might supply a new thinking for design ideal bone tissue engineering scaffolds.

本项目针对临床医学中骨缺损修复材料出现的两个难题：有机/无机材料界面结合强度弱；植入后材料/自体骨之间难形成骨性结合。基于掺锶聚磷酸钙（SCPP）促血管化作用、儿茶酚类分子粘附效果理想以及可诱导生物矿化的前期研究，提出了采用可注射骨组织工程仿生矿化支架材料的解决办法。以SCPP为无机组分，反向温敏材料聚右旋乳酸-聚乙二醇-聚右旋乳酸（PLGA-PEO-PLGA）与多巴胺合成的儿茶酚类衍生物为有机组分制备一种新型可注射骨组织工程材料。深入探索此复合支架材料中两组分之间良好界面相容性的形成机理。制得的复合支架材料通过注射方式在缺损部位形成水凝胶，且有望在植入前期仿生矿化与自体骨之间形成较好的骨性结合。本课题将系统研究这类新型支架材料结构与性能之间的关系和科学问题，探索一种具有临床应用潜力的复合支架材料，并为骨组织工程支架材料的设计提供一种新思路和新手段。

由于意外事故引起的创伤、肿瘤切除或先天缺陷等原因导致的人体骨组织的缺失是长期以来一直是威胁人类健康及明显降低病人生活质量的一个重要原因。使用骨组织工程支架材料是提供骨再生能力的主要手段。本项目针对临床医学中骨缺损修复材料出现的难题，本项目以掺锶聚磷酸钙、黑磷和埃洛石等为无机组分，胶原蛋白、丝素蛋白和聚乳酸-聚乙二醇共聚物等作为有机相。深入探索几类复合支架材料中两组分之间良好界面相容性，在植入前期仿矿化与自体骨之间形成的骨性结合及其对骨缺损再生修复的效果。本课题首先研究了多巴胺改善掺锶聚磷酸钙与胶原蛋白/丝素蛋白之间的界面结合能力、促血管化能力及促进骨再生的效果。在此基础上研究了多巴胺改善聚乳酸-聚乙二醇共聚物与掺锶聚磷酸钙之间的界面结合能力、促血管化及促进骨再生效果。本课题系统研究这支架材料结构与性能之间的关系和科学问题，并探索几种功能性骨组织工程支架材料在改善界面、促进血管化之后对骨再生修复的影响，最后，研究并提出了几种对骨再生有促进效果的策略，各种策略都取得了不同程度的修复效果，为骨组织工程支架材料的设计提供一种新思路和新手段。