载药锌合金在模拟血液流动微流控系统中的降解及药物释放研究

The traditional degradable metal materials, which are used for manufacturing intravascular stent, remain a significant problem: their life cycles hardly match the revascularization time of lesion vessels, which would extremely limit their clinical application in the interventional therapy for human artery atherosclerosis. Concerning this issue, we propose a new type of drugs loaded Zn-2Li alloy, which owns excellent mechanical properties and controllable degradation performance, as a base material for intravascular stent fabrication. This proposed project aims to study the preparation, the degradation behavior and the drug release of such drugs loaded Zn alloys. Plasma enhanced chemical vapor deposition (PECVD) and micro-emulsion methods are used to deposit multi-APTES coatings with upon drugs immobilized PEG-PLGA nanospheres. A model of internal blood circulation environment is established in a homemade microfluidic system. Consequently, the influence of environment factors (blood shear stress, blood pressure, pulsation cycle, degradation time, temperature, etc.) on the performance of drugs loaded Zn alloy will be investigated in the microsystem. Furthermore, the degradation and drugs release mechanism, the synergistic effect between substrate and coating, as well as the related kinetic models, will be respectively established. Also, the interactions between materials and blood, vascular tissues/cells will be clarified. This project would provide scientific basis for predicting and adjusting the lifetime and drug release behavior of the biodegradable implants in vitro, benefiting in the fundamental research of degradable biomaterials fabrication and performance assessment.

传统可降解金属血管支架材料（铁合金、镁合金）存在服役周期难以匹配血管恢复重建时间的问题，这极大地限制了它们在人体动脉粥样硬化介入治疗中的应用前景。针对这一问题，本项目拟开展新型的力学性能良好、可控降解的载药Zn-2Li合金支架材料制备及其降解行为、药物释放规律的研究。通过使用PECVD技术和化学合成方法，在Zn-2Li合金表面构建多层含有载药PEG-PLGA微球的APTES涂层；利用微流控技术构建模拟人体血管血液流动环境的微系统，研究血液流体剪切力、血管内压力、脉动周期、时间、温度等因素对材料降解、药物释放的影响，阐明降解、药物释放以及材料与涂层间的协同作用机理，建立相关的动力学模型；揭示材料在降解过程中与血液和血管组织/细胞的交互作用机制。本项目的研究为体外预测及调控材料的寿命周期和药物释放规律提供了理论基础和科学依据，对可降解生物材料制备及体外测试具有指导意义。

传统可降解锌合金植入体材料存在腐蚀速率与人体恢复重建速率不匹配、生物相容性不足等问题。本项目在锌合金表面构建了具有抗菌功能的高生物活性涂层以调控其腐蚀性能，最终满足人体对植入体材料的性能需求。本项目首先利用PECVD技术在锌合金表面制备了含有氨基官能团的APTES涂层，研究了等离子体沉积过程中工艺参数对涂层化学组成的影响，建立了APTES涂层在等离子体沉积过程中的生长机理，进而通过优化工艺参数获得了高密度氨基官能团。在此基础上，利用湿化学方法，将PLGA和抗菌物质负载其上，在实现抗菌性能的同时调控金属基体的腐蚀行为，同时，阐明了APTES-PLGA-抗菌物质涂层在降解过程中对细胞的影响机制。在保证良好生物相容性的同时，为提高材料的抗菌能力，设计了一系列在明、暗态下具有优异抗菌性能的g-C3N4微纳米结构涂层，并通过元素掺杂（Ag）等方法对g-C3N4电子能带结构进行优化，最终获得了可见光触发的抗菌涂层。本项目的研究成果为可生物降解材料制备以及抗菌性高生物相容性涂层的设计提供了新思路，具有一定的指导意义。在项目执行期间，项目团队在国内和国际专业期刊上发表学术论文25篇，相关成果授权国家发明专利3项，培养硕士研究生2名，目前在读硕士研究生6名，参加国内学术会议5余人次，圆满完成了项目所规定的任务。