可降解高仿生纳米复合水凝胶构建及其成骨微环境的优化在治疗骨缺损中的应用和研究

Large segmental bone defects often lead to delayed bone nonunion and fracture healing. The current bone graft material donors are limited and most of them lack biological activity, and are far from meeting the increasing clinical needs. Biologically active bone grafting materials need to be developed. Inspired by the natural bone tissue micro / nano structure, this project intends to creatively blend two kinds of bone minerals, hydroxyapatite and whitlockite, in a gelatinized methacrylate gelatin, Mesenchymal stem cells (MSCs) are encapsulated to create biologically active, three-dimensional biomimetic hydrogel with similar natural bone composition and structure. And in 3D culture, HAP can adjust gel mechanical gel stiffness, WH provide biological activity, and composite hydrogel will have controllable physicochemical characteristics to further reproduce the physiological microenvironment similar to bone tissue. This project will analyze the biocompatibility of the composite hydrogel and establish a model to study the osteogenic activity and osteoinductive activity of the composite hydrogel in vitro and in vivo. The optimal ratios of HAP and WH in the microenvironment of the biomimetic composite hydrogel are analyzed As well as validating their synergies and eventually exploring their underlying mechanisms. The bioactive three-dimensional bionic composite hydrogel with similar natural bone composition and structure to be constructed in this project will provide a new reference for the future design and manufacture of bone graft materials.

大段骨缺损常导致骨不连和骨折愈合延迟，当前的骨移植材料供体受限且大多缺乏生物活性，远不能满足日益增加的临床需求，具有生物活性的骨移植填充材料亟待开发。基于前期基础，本课题拟创造性的在甲基丙烯酸化明胶水凝胶（gelatin methacrylate）中共混两种骨矿物—纳米羟基磷灰石(HAP)和纳米白磷钙石(WH)，封装间充质干细胞（MSCs），构建3D仿生可降解类骨组成和结构的纳米复合水凝胶骨移植材料，实现快速融入缺损部位促进骨融合。在利用复合水凝胶将精准重建仿生成骨微环境中，HAP能调整机械强度，WH提供成骨活性，本课题将分析体内外系统研究复合水凝胶的成骨活性和骨诱导活性，明确仿生复合水凝胶微环境内最优HAP和WH比例以及验证其协同作用和探索其潜在机制。本课题拟构建的类似天然骨微纳结构纳米复合水凝胶将为新骨移植材料设计提供参考。

大段骨缺损常导致骨不连和骨折愈合延迟。当前自体骨移植供体受限，且大多骨填充材料缺乏生物活性，远不能满足日益增加的临床需求，具有生物活性的骨移植填充材料亟待开发。基于可控光交联GelMA水凝胶的基础，本课题在GelMA水凝胶支架中共混两种骨矿物—纳米羟基磷灰石(HAP)和纳米白磷钙石(WH)，并封装间充质干细胞（MSCs）进行三维培养，构建了类骨结构成分的仿生可降解水凝胶，确定仿生微环境中HAP和WH 3：1的最优配比，最终实现快速融入缺损部位和促进骨融合；进一步构建了GelMA基复合水凝胶并负载成骨关键的生化及物理线索以促进干细胞成骨分化，探索仿生成骨微环境对干细胞修复骨缺损领域的实际应用，在成骨生物材料和骨再生修复领域中取得重要成果。此外，本课题还结合喷涂、敷料、涂层等多种形式设计构建功能化的复合水凝胶，拓展了复合水凝胶在生物材料及骨组织工程其他领域当中的实际应用。本课题资助的创新研究成果发表于共5篇SCI论文中，其中Chemical Engineering Journal 1篇，Acta Biomaterialia 2篇，International Journal of Nanomedicine 2篇。