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

本研究采用犬下腔静脉（IVC）模型，将自体骨髓单核细胞（MN-BMCs）接种于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，构建组织工程化自体血管（TEVA）。在手术当天将该支架植入同一只狗的IVC中。植入后对TEVA进行生物化学、生物力学和组织学分析。当TEVA在1个月时用乙酰胆碱刺激和刺激时，它们剂量依赖性地产生硝酸盐和亚硝酸盐。N^G-硝基-L-精氨酸甲酯显著抑制这些反应。在乙酰胆碱的刺激下，TEVA的因子VIII阳性细胞产生eNOS蛋白，并且eNOS/s17 mRNA的比率在天然IVC、1个月和3个月TEVA之间相似。TEVA植入后6个月的生物化学性质和壁厚与天然IVC相似，并且耐受静脉压力良好，没有任何问题，如钙化。这些结果表明TEVA是具有功能性内皮细胞和生物力学性质的生物相容性材料，没有不良副作用。

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.