复合可降解高分子网络原位构建三维连通大孔磷酸钙骨水泥材料及其成骨性能研究

Calcium phosphate cement (CPC) as a bioactive material for bone repair has promising application prospect in clinic due to its characteristics of easiness to shape and self-setting ability. However, it shows too slow degradation rate and bone substitution because there are nointerconnected macroporesinside CPC, whichfor the ingrowth of new bone tissues and blood vessels. To overcome such shortage of CPC, this project aims to generate in situ interconnected macropores inside CPC by incorporating biodegradable polymer 3D-meshinto CPC, which is prepared by 3D printingwith thermoplastic polymer,by filling CPCslurry intothe 3D-mesh to obtain the polymer 3D-mesh/CPC composite material. When applied in clinic, the composite material can restore the shapability of the cement by heating itover the softening point (set value between 40 and 50C). After implantation，the polymer 3D-mesh will degrade gradually and generate in situ three-dimensionallyinterconnected macropores to provide space for the ingrowth of new bone tissues and blood vessels into the composite material. Meanwhile, the osteogenesis and vascularizationcan be promoted by doping the bioactive ionsinto CPC matrix or combining the bioactivecompounds into CPC and/or the polymer 3D-mesh. Through the synergy of the construction of the interconnected macropores and the incorporation of bioactive ingredients in the composite material,the bone substitution and the effect of bone repair will be greatly enhanced. In-depth study of the relationship between composition, structure and properties of materials will be performed and the influence of composition and structure on the material properties and theirmechanisms will be analyzed. This study will set up a new strategy to generate the 3D-interconnected macroporous structure in CPC to improve the performance of bone repair of CPC and promote its wider clinical application,which has important social and economic significance.

磷酸钙骨水泥（CPC）作为一种可塑形自固化的生物活性骨缺损修复材料，有着很好的临床应用前景。然而，CPC中无连通大孔，材料降解慢，新骨组织和血管难以长入材料内部，造成骨替代时间长，严重制约了其临床应用。本项目拟采用热塑性可降解高分子，用3D打印制备可降解高分子三维网络，通过灌注CPC浆体与高分子网络体复合。植入体内后高分子网络先期降解在CPC中原位形成三维连通大孔，为新骨长入材料内部和血管形成提供空间。同时，通过在CPC中引入活性离子和在高分子网络中载入活性物质，促进成骨和成血管能力。通过连通大孔的构建与活性成分促成骨、成血管协同配合，显著提高骨替代速度，改善骨修复效果。深入研究材料组成、结构与性能的关系，分析组成和结构因素对材料理化性能和生物学性能的影响及机制。本研究将开辟在CPC中构建三维连通大孔的新途径，对提高CPC的骨修复效果，推动其更广泛的临床应用，具有重要的社会经济价值。

磷酸钙骨水泥（CPC）具有优良的生物相容性和骨传导性以及可塑性、可注射性、原位等温固化特点，是一种性能独特的骨修复材料。然而，CPC力学性能不足，且因无连通大孔和骨诱导性导致降解速度慢、成骨能力差，严重制约了其临床应用。本项目针对CPC存在的缺点，开展了CPC复合可降解高分子三维网络并引入活性离子促成骨和成血管的研究，优选聚乳酸羟基乙酸共聚物（PLGA）作为3D打印的热塑性可降解高分子，通过优化打印条件打印出PLGA三维网络（PLGAnw）并对网络结构进行了优化，将CPC浆体灌注到PLGA网络中成功制备出PLGAnw/CPC复合材料。研究了PLGA网络结构与复合材料理化性能的关系。针对CPC抗溃散性较差的问题，进行了改善抗溃散性的研究，通过添加1%的聚丙烯酸钠和魔芋葡甘聚糖/瓜尔胶均可显著改善CPC的抗溃散性。研究了骨水泥液固比对灌注效果和复合材料结构与性能的影响，确定了适合灌注浆体的液固比。PLGAnw/CPC复合材料在50C下水浴加热1 min即可塑形，复合材料在PBS溶液中浸泡28天后PLGA网络完全降解，在CPC基体中原位形成三维连通大孔结构。为了提高磷酸钙骨水泥的成骨和成血管性能，通过CPC掺硅和复合活性离子硅酸盐化合物进行了引入活性离子促成骨和成血管的大量研究，结果表明，掺入适量的活性离子或活性离子化合物可显著促进CPC的成骨和成血管性能。创新性结合复合PLGA网络原位形成三维连通大孔及引入活性离子促成骨和成血管，制备了PLGAnw/硅酸钙/CPC复合材料和PLGAnw/硅酸钙/硅酸锌/CPC复合材料，通过动物实验验证了植入体内后PLGA网络降解原位形成三维连通大孔有利于骨组织和血管的长入，并促进成骨和成血管，显著改善了CPC的骨修复效果，为研发成骨能力优异的磷酸钙骨水泥材料打下了坚实的理论基础，有望拓展磷酸钙骨水泥的应用范围。