Ozawa Tsukasa, Mickle Donald A G, Weisel Richard D, Koyama Nobuya, Wong Harvey, Ozawa Sumiko, Li Ren-Ke
Department of Surgery, Division of Cardiovascular Surgery, Toronto General Research Institute, Toronto General Hospital, and University of Toronto, Toronto, Ontario, Canada.
J Thorac Cardiovasc Surg. 2002 Dec;124(6):1157-64. doi: 10.1067/mtc.2002.127449.
Nonbiodegradable synthetic materials have been widely used to repair cardiac defects. Material-related failures, however, such as lack of growth, thrombosis, and infection, do occur. Because a biodegradable scaffold can be replaced by the patient's own cells and will be treated as a foreign body for a limited period, we compared four biodegradable materials (gelatin, polyglycolic acid (PGA), and copolymer made of epsilon-caprolactone and l-lactic acid reinforced with a poly-l-lactide knitted [KN-PCLA] or woven fabric [WV-PCLA]) with a nonbiodegradable polytetrafluoroethylene (PTFE) material. An animal heart model was tested that simulates the in vivo clinical condition to which a synthetic material would be used.
The five patches were used to repair transmural defects surgically created in the right ventricular outflow tracts of adult rat hearts (n = 5, each patch group). The PTFE patch group served as a control group. At 8 weeks after implantation, the biomaterials were excised. Patch size, patch thickness, infiltrated cell number, extracellular matrix composition, and patch degradation were evaluated.
The PTFE patch itself did not change in size except for increasing in thickness because of fibroblast and collagen coverage of both its surfaces. Host cells did not migrate into the PTFE biomaterial. In contrast, cells migrated into the biodegrading gelatin, PGA, and KN-PCLA and WV-PCLA scaffolds. Cellular ingrowth per unit patch area was highest in the KN-PCLA patch. The KN-PCLA patch increased modestly in size and thinness. The WV-PCNA patch did not change in size or thickness. Fibroblasts and collagen were the dominant cellular infiltrate and extracellular matrix formed in the biodegrading scaffolds. The in vivo rates of biomaterial degradation, thinning, and expansion were material specific. All the subendocardial patch surfaces were covered with endothelial cells. No thrombi were seen.
The unique, spongy matrix structure of the PCLA patch favored cell colonization relative to the other patches. The strong, durable outer poly-l-lactide fabric layers in these patches offered physical, biocompatible, and bioresorbable advantages relative to the other biodegradable materials studied. Host cells migrated into all the biomaterials. The cells secreted matrix and formed tissue, which was endothelialized on the endocardial surface. The biomaterial degradation rates and the tissue formation rates were material related. The PCLA grafts hold promise to become a suitable patch for surgical repair.
不可生物降解的合成材料已被广泛用于修复心脏缺损。然而,确实会出现与材料相关的失败情况,如生长不足、血栓形成和感染。由于可生物降解的支架可以被患者自身的细胞替代,并且在有限的时间内会被视为异物,我们将四种可生物降解材料(明胶、聚乙醇酸[PGA]以及由ε-己内酯和左旋乳酸制成并由聚左旋丙交酯针织[KN-PCLA]或机织[WV-PCLA]增强的共聚物)与一种不可生物降解的聚四氟乙烯(PTFE)材料进行了比较。测试了一种动物心脏模型,该模型模拟了合成材料将被应用的体内临床状况。
使用这五种补片对成年大鼠心脏右心室流出道手术造成的透壁缺损进行修复(每组补片n = 5)。PTFE补片组作为对照组。植入8周后,切除生物材料。评估补片大小、补片厚度、浸润细胞数量、细胞外基质组成和补片降解情况。
PTFE补片本身大小未变,只是由于其两面有成纤维细胞和胶原蛋白覆盖而厚度增加。宿主细胞未迁移到PTFE生物材料中。相比之下,细胞迁移到了可生物降解的明胶、PGA以及KN-PCLA和WV-PCLA支架中。单位补片面积的细胞向内生长在KN-PCLA补片中最高。KN-PCLA补片的大小和厚度适度增加。WV-PCNA补片的大小和厚度未变。成纤维细胞和胶原蛋白是在可生物降解支架中形成的主要细胞浸润和细胞外基质。生物材料在体内的降解、变薄和扩张速率因材料而异。所有心内膜下补片表面均覆盖有内皮细胞。未见血栓形成。
相对于其他补片,PCLA补片独特的海绵状基质结构有利于细胞定植。这些补片中坚固、耐用的外层聚左旋丙交酯织物层相对于其他研究的可生物降解材料具有物理、生物相容性和生物可吸收性优势。宿主细胞迁移到所有生物材料中。细胞分泌基质并形成组织,该组织在心内膜表面内皮化。生物材料的降解速率和组织形成速率与材料有关。PCLA移植物有望成为一种适合手术修复的补片。