TISSUE ENGINEERING CARDIOVASCULAR STRUCTURES

各种血管移植物常用于心血管组织的重建。然而，目前使用的假体或生物假体材料缺乏生长潜力，因此，随后需要在儿科患者成熟时进行替换。组织工程(TE)是一门新兴学科，它提供了从自体细胞和可生物降解的聚合物支架创建替代结构的可能性。因为TE结构包含活细胞，所以它们可能具有生长、自我修复和自我重塑的潜力。将4~6×10~(-6)的杂种犬股静脉混合细胞接种到由聚乙醇酸无纺布片材和L-丙交酯-己内酯共聚物(n=4)组成的管状可生物降解聚合物支架上，制成组织工程血管自体移植物。7天后。用TEVA代替同一只犬的下腔静脉(IVCs)。术后3、4、5、6个月行血管造影。狗是…更多的人牺牲了。对植入的TEVA进行大体和免疫组织学检查。植入的TEVA显示没有狭窄或扩张的迹象。未经任何抗凝治疗，TEVA内未发现血栓。没有在所有的标本中观察到聚合物支架的残留物，总体外观看起来与天然的静脉内皮细胞相似。免疫组织化学染色显示视网膜腔表面有因子阳性的有核细胞。此外，还观察到存在α-平滑肌肌动蛋白和结蛋白阳性细胞的病变。植入的TEVA含有足够数量的细胞外基质，既没有闭塞，也没有形成动脉瘤。此外，还发现内皮细胞排列在每个TEVA的管腔表面。这些结果有力地表明，可以制造出具有抗血栓形成能力的理想的静脉移植物。使用TE技术。用自体静脉细胞成功地重建了一例4岁女孩的外周肺动脉。用TE血管移植重建闭塞的肺动脉。无术后并发症发生。在后续的血管造影术中，移植的血管完全通畅。要证实这种方法的可行性，显然有必要进行长期随访。然而。鉴于我们的成功，我们现在计划继续在静脉或肺循环等低压血管中使用这项自体细胞TE技术。由于我们的实验室和临床经验都是令人鼓舞的，我们认为TE入路可能在儿童心血管外科领域作为移植和人工器官使用的一种替代方法发挥重要作用。较少

Various vascular grafts are commonly used in the reconstruction of cardiovascular tissues. However, currently used prosthetic or bioprosthetic materials lack growth potential and, therefore, subsequently require replacement in pediatric patients as they mature. Tissue engineering (TE) is a new discipline that offers the potential to create replacement structures from autologous cells and biodegradable polymer scaffolds. Because TE constructs contain living cells, they may have the potential to grow, self-repair, and self-remodel. Tissue Engineered Vascular Autografts (TEVAs) were made by seeding 4-6 x 10^6 of mixed cells obtained from femoral veins of mongrel dogs onto tube-shaped biodegradable polymer scaffolds composed of a polyglycolic acid (PGA) non-woven fabric sheet and a co-polymer of l-lactide and- caprolactone (N=4). After 7 days. the inferior vena cavas (IVCs) of the same dogs were replaced with TEVAs. After 3, 4, 5 and 6 months, angiographies were performed. and the dogs wer … More e sacrificed. The implanted TEVAs were examined both grossly and immunohistologically. The implanted TEVAs showed no evidence of stenosis or dilatation. No thrombus was found inside the TEVAs, even without any anticoagulation therapy. Remnants of the polymer scaffolds were not observed in all specimens, and the overall gross appearance appeared similar to that of native IVCs. Immunohistological staining revealed the presence of Factor VIII positive nucleated cells at the luminal surface of the TEVAs. In addition, lesions were observed where α-smooth muscle actin and desmin positive cells existed. Implanted TEVAs contained a sufficient amount of extracellular matrix, and showed neither occlusion nor aneurysmal formation. In addition, endothelial cells were found to line the luminal surface of each TEVA.These results strongly suggest that 'ideal' venous grafts with anti-thrombogenicity can be produced. Using the TE technique. a peripheral pulmonary artery was successfully reconstructed in a 4-year-old girl using autologous venous cells. The occluded pulmonary artery was reconstructed with the TE vessel graft. No postoperative complications occurred. On follow-up angiography, the transplanted vessels was noted to be completely patent. Long-term follow up is obviously necessary to confirm the feasibility of this approach. However. given our success, we now plan to continue to use this TE technique with autologous cells in only low pressure vessels, such as the venous or pulmonary circulation. Because both our laboratory and clinical experiences are quite encouraging, we suggest that the TE approach may play an important role as an alternative method to transplantation and to the use of artificial organs in the field of pediatric cardiovascular surgery. Less