镁合金支架材料表面新型仿生纳米功能涂层的研究

Magnesium (Mg) alloys, thanks to their biodegradability, biocompatibility and mechanical properties, show great promise as next-generation vascular stents for the invasive treatment for stenosis. However, the major limitations lie in the fast degradation of Mg matrix, as well as the high rate of in-stent restenosis post implantation. As the current approach of applying drug-eluting coatings to stents (DES) is likely to cause thrombosis and other serious issues, in this study, we propose a new strategy of engineering a novel nanoscale biomimetic surface modification to promote cell adhesion and proliferation of vascular endothelial cells while inhibiting those of smooth muscle cells, thus to promote re-endothelialization and to decrease the rate of restenosis post stent implantation. We first plan to prepare a polydopamine (PDA) layer onto Mg alloy substrates, followed by the design and synthesis of a series of graft polymers with specific short peptides for the secondary functionalization of the PDA layer, thus to achieve a novel nano-coating owning multi-functionality of corrosion protection for Mg matrix, and selective cell adhesion to endothelial cells rather than smooth muscle cells. Moreover, the performance of Mg alloys modified with this coating in terms of degradation, biocompatibility, re-endothelialization and other properties will be intensively studied and evaluated both in vitro and in vivo. This study will not only provide in-depth investigations of the biointerfacial interactions and the involving mechanism of this coating material, but also offer a theoretical and technical basis for the development of promising vascular stents with greater performance.

医用镁合金因其可完全降解、生物相容性好、适宜的力学性能等特性而有望成为新一代血管支架材料来治疗血管狭窄性病变。但基体降解速率较快以及支架植入术后再狭窄率较高是尚未得到有效解决的重要问题。本项目摒弃了目前存在不少副作用的加载药物洗脱涂层的方法，而拟通过支架材料表面的纳米仿生修饰的策略来促进血管内皮细胞的粘附和增殖、同时抑制平滑肌细胞的粘附和增殖，进而促进再内皮化、降低再狭窄率。拟在镁合金基底上制备具有优异生物相容性的聚多巴胺层，并设计和合成一系列接有特异性短肽的接枝聚合物进行聚多巴胺层的二次功能化，从而获得具有一定腐蚀保护性、并能选择性粘附血管内皮细胞的纳米仿生功能涂层。在耐腐蚀保护性、生物相容性、再内皮化等方面对修饰该涂层的镁合金材料进行体内外全方位研究和考察。本项目不仅会从分子层面深入研究和揭示该支架涂层材料的生物表界面行为和机理，而且将为研发性能更为优越的血管支架奠定理论和技术基础

医用镁合金因其可完全降解、生物相容性好、适宜的力学性能等特性而有望成为新一代血管支架材料来治疗血管狭窄性病变。但镁基体降解速率较快以及支架植入术后再狭窄率较高是尚未得到有效解决的重要问题。本项目摒弃了目前存在不少副作用的加载药物洗脱涂层的方法，而创新性的通过支架材料表面的纳米仿生修饰的策略来调控镁基体降解、同时促进血管内皮细胞的粘附和增殖而抑制平滑肌细胞的粘附和增殖，进而促进再内皮化、降低再狭窄率。项目首先探索了在镁合金基底上通过无水溶剂中多巴胺聚合反应首次制备出致密、完备的带负电的聚多巴胺纳米层，具有高结合强度、优异生物相容性，且能显著降低基体腐蚀速率，并研究了聚多巴胺层通过带负电网络结构阻滞氯离子进攻、抑制电荷转移的抗腐蚀机制。在抗腐蚀的基础上，课题进一步设计和合成了接有特异性短肽的水凝胶高分子层进行聚多巴胺层的二次功能化，从而获得了能选择性粘附血管内皮细胞、抑制平滑肌细胞的纳米仿生功能涂层，体外验证对两种细胞选择性效果理想,并从蛋白选择性吸附角度研究了其中的机理。我们还在耐腐蚀保护性、生物相容性、再内皮化等方面对修饰该涂层的镁合金材料进行了动物体内（兔子）全面研究和考察，验证了其生物功效优越性。本项目不仅从分子和细胞层面深入研究和揭示了该支架涂层材料的生物表界面行为和机理，而且为研发性能更为优越的血管支架奠定了理论和技术基础。