van der Giessen W J, Lincoff A M, Schwartz R S, van Beusekom H M, Serruys P W, Holmes D R, Ellis S G, Topol E J
Department of Cardiology, Erasmus University Rotterdam, The Netherlands.
Circulation. 1996 Oct 1;94(7):1690-7. doi: 10.1161/01.cir.94.7.1690.
With the thrombogenic tendency and permanent implant nature of metallic stents, synthetic polymers have been proposed as candidate materials for stents and local drug delivery designs. We investigated the biocompatibility of several synthetic polymers after experimental placement in the coronary artery.
Five different biodegradable polymers (polyglycolic acid/polylactic acid [PGLA], polycaprolactone [PCL], polyhydroxybutyrate valerate [PHBV], polyorthoester [POE], and polyethyleneoxide/polybutylene terephthalate [PEO/ PBTP]) and three nonbiodegradable polymers (polyurethane [PUR], silicone [SIL], and polyethylene terephthalate [PETP]) were tested as strips deployed longitudinally across 90 degrees of the circumferential surface of coil wire stents. Appropriately sized polymer-loaded stents were implanted in porcine coronary arteries of 2.5- to 3.0-mm diameter. Four weeks after implantation, stent patency was assessed by angiography followed by microscopic examination of the coronary arteries. The biodegradable PCL, PHBV, and POE and the nonbiodegradable PUR and SIL evoked extensive inflammatory responses and fibrocellular proliferation (thickness of tissue response: 0.79 +/- 0.22, 1.12 +/- 0.01, 2.36 +/- 0.60, 1.24 +/- 0.36, and 1.43 +/- 0.15 mm, respectively). Less but still severe responses were observed for the biodegradable PGLA and PEO/PBTP (0.46 +/- 0.18 and 0.61 +/- 0.23 mm, respectively) and for the nonbiodegradable PETP (0.46 +/- 0.11 mm).
An array of both biodegradable and nonbiodegradable polymers has been demonstrated to induce a marked inflammatory reaction within the coronary artery with subsequent neointimal thickening, which was not expected on the basis of in vitro tests. The observed tissue response may be attributable to a combination of parent polymer compound, biodegradation products, and possibly implant geometry.
鉴于金属支架的血栓形成倾向和永久植入性质，合成聚合物已被提议作为支架及局部药物递送设计的候选材料。我们在冠状动脉中进行实验性植入后，研究了几种合成聚合物的生物相容性。
五种不同的可生物降解聚合物（聚乙醇酸/聚乳酸[PGLA]、聚己内酯[PCL]、聚羟基丁酸戊酸酯[PHBV]、聚原酸酯[POE]以及聚环氧乙烷/聚对苯二甲酸丁二醇酯[PEO/PBTP]）和三种不可生物降解聚合物（聚氨酯[PUR]、硅酮[SIL]以及聚对苯二甲酸乙二酯[PETP]）被制成条带进行测试，这些条带纵向横跨螺旋钢丝支架圆周表面的90度。将尺寸合适且加载了聚合物的支架植入直径为2.5至3.0毫米的猪冠状动脉中。植入四周后，通过血管造影评估支架通畅情况，随后对冠状动脉进行显微镜检查。可生物降解的PCL、PHBV和POE以及不可生物降解的PUR和SIL引发了广泛的炎症反应和纤维细胞增殖（组织反应厚度分别为：0.79±0.22、1.12±0.01、2.36±0.60、1.24±0.36和1.43±0.15毫米）。对于可生物降解的PGLA和PEO/PBTP（分别为0.46±0.18和0.61±0.23毫米）以及不可生物降解的PETP（0.46±0.11毫米），观察到的反应较轻但仍较为严重。
已证明一系列可生物降解和不可生物降解的聚合物在冠状动脉内会引发明显的炎症反应，并随后导致新生内膜增厚，而这在体外测试中并未预料到。观察到的组织反应可能归因于母体聚合物化合物、生物降解产物以及可能的植入物几何形状的综合作用。
