生物可降解材料聚乳酸/聚羟基乙酸复合壳聚糖在人工冠状动脉血管支架制备中的应用

第一代金属裸支架和第二代涂层支架介入治疗冠状动脉粥样硬化性心脏病(冠心病)已得到广泛应用。由于长期存在金属支架异物刺激及其携带的药物扰乱血管壁各层细胞生长,引起支架内再狭窄和血管栓塞,远期仍有较多的主要心血管不良事件发生和需要再血管化治疗。因此,由聚酯、聚碳酸酐及聚磷酸酯等高分子材料制备的完全可生物降解吸收支架及药物洗脱支架应运而生,其中聚乳酸(poly-lactic acid,PLA)、聚羟基乙酸(poly-glycolicacid,PGA)、壳聚糖、聚己内酯(poly-caprolactone,PCL)及一些共聚物如聚乳酸/聚羟基乙酸共聚物(poly-lactic-co-glycolic acid,PLGA)材料制备的心血管植入支架的安全性、组织及血液相容性已得到证实,然而这些支架具有各自的缺点,如PLA降解较慢质硬易断裂柔韧性不足,PGA降解较快质软支撑力不足,支架降解太快或者太慢,均难以达到有效支撑,支架植入后容易出现血管损伤、弹性回缩,导致血管再狭窄及血栓形成,远期效果不佳。通过优化组合不同摩尔比的PLA和PGA及壳聚糖涂层,可以获得具有更好的生物相容性、适度的降解速率(约3～6个月完全降解)、足够的机械强度、较低的炎症反应和伸展度良好的复合材料,从而为制备完全生物可降解冠状动脉支架奠定实验基础。

Artificial Coronary Vascular Stents Fabrication Using Biodegradable Material Compounds of PLA/PGA-co-Chitosan

The first generation scaffolds of bare metal stents(BMS) and the second generation of drug eluting stents(DES) have been widely used in the treatment of coronary heart diseases.However,long term incidences of major adverse cardiovascular events and revascularization treatments are still high because of in-stent re-stenosis and thrombosis.These may be caused by chronic inflammations and vascular wall damages due to persistent metal stents stimulation.What’s more,the eluting drugs within metal stents could also disturb normal growth of vascular endothelial cell,intima,tunica media,smooth muscle and epimysium.Therefore,in order to meet these demands several fully biodegradable scaffolds and drug carried stents have been manufactured using polymers polyester,polycarbonate and polyphosphate,etc.Among them,the security and histo-and hemo-compatibilities of coronary scaffolds made from poly-lactic acid(PLA),poly-glycolic acid(PGA),chitosan as coating,poly-caprolactone(PCL) and other copolymer like poly-lactic-co-glycolic acid(PLGA) have been testified to be sound.Nevertheless,there exist several different shortages for these stents such as tensile strength deficiency and slow degradation.PLA is hard and brittle with slow degradation,while PGA is soft with insufficient support force and fast degradation.Whether stents degrade too fast or too slow,they could not supply sufficient strength and effective support after implantation,and also they may cause target vascular injuries and elastic shrink inducing restenosis and thrombosis in long terms.Using optimized molar ratio component of PLA and PGA with chitosan coating,we can get sound composite materials with better biocompatibility,moderate degradation(approximately 3-6 months of complete degradation),adequate mechanical strength,lower inflammatory response and good range of extension,and establish an experiment ground for fully biodegradable vascular scaffolds fabrication.