Development, Analyze and Clinical Use of Tissue Engineering Large Diameter Autografts

以犬下腔静脉为模型，对自体单核骨髓细胞(MN-BMC)和可生物降解支架构建的组织工程血管自体移植物(TEVA)进行了评价。MN-BMC取自犬下腔静脉，种植在由聚乙交酯纤维和聚(1-丙交酯-co-ε-己内酯)海绵组成的可生物降解管状支架上。手术当天，将该支架植入同一只狗的下腔静脉。植入后对TEVA进行生化、生物力学和组织学分析。当TEVA移植并在1个月时用乙酰胆碱刺激时，它们会产生剂量依赖性的硝酸盐和亚硝酸盐。N、G-硝基-L-精氨酸甲酯对上述反应有明显的抑制作用。在乙酰胆碱刺激下，第VIII因子阳性的Tevas细胞产生eNOS蛋白，而天然IVC、1月龄和3月龄Tevas的eNOS/S17mRNA比值相近。在植入后6个月，TEVA的生化特性和管壁厚度与天然IVC相似，对静脉压力的耐受性良好，无钙化等问题，说明TEVA是一种与功能内皮细胞和生物力学性能良好且无不良副作用的生物相容性材料。

This study demonstrates the evaluation of tissue-engineered vascular autografts (TEVAs) constructed with autologous mononuclear-bone marrow cells (MN-BMCs) and a biodegradable scaffold using a canine inferior vena cava (IVC) model.MN-BMCs were obtained from a dog and seeded onto a biodegradable tubular scaffold consisting of polyglycolide fiber and poly(1-lactide-co-ε-caprolactone) sponge. This scaffold was implanted in the IVC of the same dog on the day of surgery. TEVAs were analyzed biochemically, biomechanically and histologically after implantation. When TEVAs were explanted and stimulated with acetylcholine at 1 month, they dose dependently produced nitrates and nitrites. N^G-nitro-L-arginine methylester significantly inhibited these reactions. On the stimulation by acetylcholine, factor VIII-positive cells of TEVAs produced eNOS proteins, and the ratio of eNOS/s17 mRNA were similar among native IVC, 1-and 3-months TEVAs. TEVAs had similar biochemical properties and wall thickness as native IVC at 6 months after implantation, and tolerated venous pressure well without any problems such as calcification.These results indicate that TEVAs are biocompatible material with functional endothelial cells and biomechanical properties without unwanted side-effects.