完全生物可降解PTMC-LLA-GA三元共聚物的设计及其3D打印制作血管支架结构与性能的研究

A series of poly(trimethylene carbonate) (PTMC) will be synthesized by ring opening polymerization (ROP) as a macroinitiator. The reactivity of PTMC will then be enhanced by functionalization of the ending groups. These functionalized PTMC prepolymer could act as efficient initiators in the ring opening polymerization of various molar ratios of L-lactide (LLA) and glycolide (GA) to prepare PTMC-LLA-GA terpolymers with specially segments configuration at relative low temperatures. Compared with poly(L-lactic acid)(PLLA), the novel PTMC-LLA-GA material will have a high strength, good toughness and optimized degradation rate among its other advantages. The molecular weight of PLLA-TMC-GA terpolymers and its segment configuration will be optimized by careful design of the ROP procedures. The thermodynamic parameters and kinetics of the crystallization process and the morphology of the crystalline will be obtained, which will allow us to better understand the mechanisms of crystallization of PTMC-LLA-GA terpolymers. Further, the relationship between the chain microstructure and the material properties including the mechanical behavior, enzymic degradation and biocompatibility will be studied systematically to prepare materials with high number average molecular weight and optimized thermal, mechanical and degradability properties. In the cardiovascular stent of totally biodegradable polymers materials, the innovative results will be achieved. On the basis of our previous work, cardiovascular stents of totally biodegradable PTMC-LLA-GA terpolymers will be prepared by rapid three-dimensional (3D) printing processes. Effects of the chemical composition, condensed status and microstructure of PTMC-LLA-GA terpolymer, and the printed stent construction on the performances of PTMC-LLA-GA stents, including mechanical properties, enzymatic and hydrolytic degradation behaviorsand the biocompatibility, will be investigated by various techniques. The materials composition and chain microstructure, the stent structures and the 3D printing process will be optimized to obtain the most favorable fabrication conditions for an innovative stent. Furthermore, the project will provide a mechanistic understanding on the effects of material composition and the stent hierarchical structure from the bulk to micro-scale on the final stent performance, establishing a theoretical foundation and experimental basis for high performances biodegradable polymer stents. In the research field of totally biodegradable polymers as cardiovascular stent, this project will establish a new approach in developing novel and cost-effective synthesis and manufacture techniques with our own complete intellectual properties.

本项目拟开环聚合聚三亚甲基碳酸酯预聚物，采用链端基活化法，提高其反应活性，在较低的温度下再与左旋乳酸、乙交酯开环无规共聚，制备强度高、韧性好和降解速度可控的链段构型独特的三元共聚物。重点研究合成条件对共聚物的分子量、序列结构的影响；研究材料的结晶热力学、动力学及形态，揭示其结晶机理；阐明其微观结构对材料力学、降解及生物性能的影响，在高分子量、序列结构可控和性能优的完全可生物降解聚合物材料研究中有所突破。在此基础上，对材料采用3D打印制备血管支架的结构与性能进行研究。主要研究材料的化学结构、凝聚态及结构对其力学、降解和生物性能等的影响，阐明材料微观结构对支架性能影响的机理，为综合性能优的3D打印完全可降解聚合物血管支架研究奠定理论基础和实验依据；通过对材料化学组成、微结构和支架构造及其成型最优化研究，筛选出支架最佳制备条件和工艺。为拥有自主知识产权的完全生物可降解聚合物支架开发有所贡献。

基于分子链构型设计的理念，开环聚合制备了三个系列结构的PTMC-LLA-GA三元共聚物，即无规共聚物、聚三亚甲基碳酸酯-(聚丙交酯/乙交酯无规)嵌段共聚物(P(TMC-b-(LLA-r-GA)))和聚(三亚甲基碳酸酯/乙交酯)-(聚丙交酯/乙交酯无规)双嵌段共聚物(P((TMC-r-GA)-b-(LLA-r-GA)))完全可降解的PTMC-LLA-GA新材料。对PTMC-LLA-GA三元共聚物分子量和结构控制的合成技术进行了优化。通过对材料微结构与性能详实研究，阐明了非晶的柔性链段对材料的增韧机制，从韧性和强度上增强了血管支架材料的机械性能。揭示了GA组分对共聚物链段序列结构及对材料降解速率的调控机制，开发出数均分子量高、强度高、韧性好、结构和降解速度可调控的的PTMC-LLA-GA完全生物可降聚合物材料。为拥有知识产权的新一代完全可降解高性能血管支架或组织工程器械的开发奠定了基础。.项目采用3D打印技术制备了PTMC-LLA-GA完全生物可降聚合物的血管支架，并对支架材料结构与其性能进行研究。通过对3D打印加工不同组成和分子量调控的链段序列结构演变及性能评估，揭示了PTMC-LLA-GA三元共聚物化学组成、凝聚态对其力学、降解和生物性能等的影响机制，阐明了材料微观结构对支架性能影响的机理，为高性能可降解聚合物血管支架开发提供了理论与实验依据。.此外，项目等离子表面处理原位聚合方法，分别用明胶或聚N-异丙基丙烯酰胺(PNIPAAm)对PTMC-LLA-GA三元共聚物材料表面进行涂层修饰，增强材料的生物相容性和细胞再生性，为具有表面载药并缓释的药物洗脱功能血管支架的提供一条新的技术路线。项目还采用固相拉伸技术，利用其微结构与仿生表面特性，开发了具有优异力学和生物性能的完全可降解长链枝化PLLA材料，能够满足血管支架和组织工程植入器械材料的要求，具有很强的应用前景。.项目取得的研究成果，可为综合性能优的可生物降解的聚合物设计、合成及其结构与性能机理和实验技术的发展提供新思路，为新型完全可降解高分子血管支架开发奠定了理论基础和实验依据。