新型仿生自扩展可降解心血管医用植入材料的研究

Cardiovascular disease is the leading causes of death worldwide. Percutaneous transluminal coronary angioplasty (PTCA), which is based on a non-degradable metal stent implantation, has been an important procedure in the treatment of cardiovascular diseases. However, in-stent thrombosis and restenosis are still significant concerns in its clinical application. A new type of biodegradable stent with good antithromboticity and anti- restenosis are believed to provide better alternative for metal stent implantation..Nitric oxide (NO) is well known as a potent anti-platelet agent and an effect inhibitor of smooth muscle cell (SMC) proliferation. The project will explore the possibility of fabrication of core-shell nanofiber via coaxial electrospinning as a new strategy to in-situ generates NO for cardiovascular application. A biodegradable biselenide polymer, which mimics glutathione peroxides (GPx) catalytic center to catalytic generating NO from endogenous donors, will be synthesized as the shell materials. Then the core-shell nanofiber of PCL based polymer will be fabricated via coaxial electrospinning. The shell will provide the biselenide(—SeSe—) GSH-Px mimic catalytic center to in-situ generate enough NO from endogenous donors for anti-thrombgenic. The core, which is the exogenous NO donors doped polymer, can be explored as a reservoir of the exogenous NO donors. The local delivery of exogenous NO donors, which combining with the endogenous donors, can be regulated to a suitable NO for SMCs inhibition and anti-restenonsis..Furthermore, taking the advantage of an electrospinning technique, a self-expanding implantation of cardiovascular stent will be explored via asymmetric electrospinning. The inner side of the stent is hydrophilic while the outer side of the stent is superhydrophobic. The effect of asymmetric structure to amplify the shape memory will be investigated and further explore the possibility of developing automatically self-expand stent after implantation due to the humido-responsive properties.

心血管疾病已成为人类的“第一杀手”。现代介入医用材料和器械使用，极大地丰富了心血管疾病的治疗手段。为根本解决心血管支架植入后中远期血栓和再狭窄问题，发展具有内皮愈合功能的全降解心血管植入器件成为关键。本项目针对全降解心血管植入器件制备和临床实现的关键问题，结合研究团队特色性的仿生界面理论和技术，发展NO量化控释技术和基于电纺的多元微纳调控技术，深入研究多元仿生结构调控血管内皮复杂体系竞争性生长的基本规律，为制备具有内皮再生功能的全降解心血管植入材料和器件奠定基础；并进一步针对全降解支架加工和临床植入的难题，探索采用多层不对称电纺技术制备具有湿度－温度双重响应形状记忆功能的新型心血管植入器件，为实现全降解聚合物支架的自扩展植入提供全新的途径。

本项目针对具有内皮愈合功能的全降解心血管植入器件的关键问题，结合血管植介入材料“从简单机械力学支撑向个性化力学操作发展”，“从生物相容向组织诱导再生发展”的两大趋势，将形状记忆聚合物、界面仿生组装和修饰及材料自愈合设计原理有机整合，开展了新型心血管植介入材料和装置的研究，取得了以下成果：.1）深入研究了多元仿生结构调控血管细胞竞争性生长和内皮功能的基本规律，发现并证明了材料界面硬度微环境对内皮细胞功能的关键作用，丰富了特色性的血管内皮原位再生原理；并进一步建立了包括NO量化控释，多巴胺仿生界面修饰和表面介导基因等内皮原位再生功能涂层设计新方法；为制备具有内皮再生功能的全降解心血管植入材料和器件奠定了基础。.2）将静电纺丝技术和3D打印技术结合，成功制备了具有湿度－温度双重响应形状记忆功能的新型自扩展心血管植入支架，并进一步结合血管微创植介入装置个性化微操作要求，将光热转化技术和形状记忆材料结合，建立了一种“按需刻写”的新型形变调控方法，为设计具有形状调控功能的新型植介入材料提供了可能。.3）结合血管植入材料的临床应用性和市场准入的可行性，将具有湿度响应功能的聚电解质自愈合特性巧妙应用到聚电解质涂层制备中，发明了聚电解质复合物自愈合涂层技术，成功将特色性的层状仿生设计原理转化为可通过工业喷涂设备实现的生物活性大分子涂层技术；并进一步发明了具有动态自愈合特性的多孔海绵涂层技术，建立了一种“On-demand”多功能涂层设计新策略，成功制备了具有血管原位再生功能的新型全降解聚合物支架；.以上研究成果在Advanced Fuctional Materials, Materials Horizons, Biomaterials等杂志上发表论文43篇，申请国家发明专利9项，获国家发明专利8项，形成了针对具有组织再生功能的新型全降解血管支架的专利保护群。其中，表面介导基因涂层支架和基于自愈合多孔海绵涂层的新型内皮原位再生全解聚合物支架完成动物实验，进入临床前评估阶段。