具有生物降解可控性的组织修复聚氨酯支架材料的研究

The controlled degradation of scaffold materials for tissue repair is one of the most popular topics in the modern tissue engineering, and matching the degradation rate of scaffold materials with the repairing process of the tissue is one of the pressing puzzles in the tissue repair engineering. In my present, to meet the requirement of the controlled degradation of scaffold material in tissue repair, we will design and prepare a series of novel biodegradable polyurethanes, which have good designable ability of polymer molecules and their degradation properties can be quantitatively accommodated by accurately altering the molecular weight of soft segment, the ratio of soft segment/hard segment and the types of feedstock. Then, the three-dimensional (3D) scaffolds based on the biodegradable polyurethane, posse controlled porosity, will be prepared by selective laser sintering. The pore size of 3D scaffolds will be evaluated by scanning electron microscope and liquid replacement method and the mechanical properties of 3D scaffolds will be characterized by mechanical tensile testing. The cell morphology, cell attachment and spreading, cell proliferation, cell differentiation and mineralization ability were systemically detected to indicate the cytocompatibility of 3D scaffolds. Moreover, in order to collect the integrated and accurate data of the degradation properties, the biodegradation of 3D scaffolds will be investigated. The important factors, especially cell participating, will be clarified. Finally, based on the results of the degradation research of 3D scaffolds, we will carry out the experiment of repairing radius of the rabbit using the 3D scaffolds, which have the suitable degradation rate to match the radius repairing. These results will illuminate the mechanism of matching the degradation rate of scaffold materials with the repairing process of the tissue and confirm the controlled degradation rate of 3D scaffold is very important for tissue repairing.

组织修复支架材料的降解可控性研究是现代组织工程研究的热点领域之一，而支架材料的降解速率与组织愈合过程的相匹配问题是组织修复工程亟待解决的难题之一。本课题调节具有分子可设计性的可降解聚氨酯材料的原料类型及软硬段比例，精确地控制材料链段中具有不同降解性能的化学键型的含量，从而获得具有可控生物降解性能的聚氨酯修复支架材料。利用选择性激光烧结技术制造具有可控孔隙率的3D修复支架，评价其参数、力学性能和细胞相容性。通过用模拟组织环境（细胞参与）的实时降解试验，阐明影响3D支架材料降解的关键因素，提供支架材料准确的降解数据，为支架材料降解性能与组织修复相匹配的机制研究作铺垫。以3D支架材料具有可控的生物降解性能为基础，进行骨组织缺损修复研究，证明支架材料降解速率与组织愈合速率相匹配的重要性，对揭示支架材料的降解速率与组织愈合速率相匹配机制有重要意义，为组织修复工程临床化奠定重要的理论基础。

本课题基于组织修复过程中支架材料代谢与组织生长相匹配的关键基础科学问题，提出设计新型具有生物降解可控的聚氨酯生物材料，以匹配待修复组织生长过程所需，并结合先进三维打印技术制造三维修复支架，拟应用于组织修复工程应用中。.围绕该课题中心思路，首先展开了新型聚氨酯医用材料——哌嗪基聚氨酯生物材料（Piperazine-based polyurethane-ureas, P-PUUs）的降解性能研究，重点考察其生物降解可控性。检测P-PUUs材料在降解过程中的分子量及力学性能的变化，并归纳其降解过程中的降解速率。通过理论计算和实验分析相结合，将材料本体性质与其降解过程中的变化联系起来，获得P-PUUs材料可控降解的量化结果，使我们对该类材料的降解机制有了更深入的了解；其次，构建具有降解可控特性的三维组织修复支架。采用三维打印技术(3D printing)取代选择性激光烧结（SLS）技术对P-PUUs材料的三维支架进行设计与制造，并对支架性能进行了相关表征；最后，对修复支架材料进行体内动物实验，进一步评估其体内成骨及体内材料降解性能。.同时，在项目研究过程中，还关注到作为组织修复材料，在实际临床应用中遇到一些困难（如术后感染引起的炎症反应及微创植入等）。因此，基于本课题聚氨酯材料优势，且结合聚氨酯材料具有良好可设计性，通过设计其主链结构，从而赋予其多重功能，获得更多新型生物医用材料，进一步扩展项目实施意义。.总之来说，经过本项目3年实施期的执行，团队努力奋斗，保质保量完成了该项目进度，达到了本项目预期目标，如下：.1）成功建立定量控制聚氨酯生物材料组分的设计方案，实现了定量调控聚氨酯材料的理化性质；.2）基本阐明生物材料生物降解性能研究的关键影响因素，建立生物降解性能评估标准；.3）运用三维打印技术成功构建降解可控三维组织修复支架，并进一步体内探索其相匹配的机制；.4）在P-PUUs材料体系基础上，成功研发2种新型可降解性能优异材料，旨在进一步提高修复支架材料性能，推动其临床应用。.5）发表SCI收录论文4篇，另有3篇相关SCI论文在投；并申报国家发明专利3项，1项授权；联合培养学生2名，培养青年科技学者3名；应邀参加学术会议5次，并作相关学术展示。