Clinical Application of Tissue Engineered Vascular Autograft using Autologous Bone Marrow Cells and Biodegradable Scaffolds

本研究证明了组织工程血管自体移植物（TEVA）的内皮功能和机械性能的评价与自体单核骨髓细胞（MN-BMC）和可生物降解的支架使用犬下腔静脉（IVC）模型。MN-BMCs从狗获得并接种到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的管状支架上。在手术当天将该支架植入同一只狗的IVC中。植入后1、3、6和12个月观察，TEVA（直径8 mm，长2cm）内表面有内皮细胞覆盖，并进行生化、生物力学和组织学分析。组织学上，平滑肌细胞、胶原纤维和弹性纤维。其构成血管壁，在植入后随时间逐渐增加。植入一年后的标本显示成熟的血管样结构。TEVA的机械性能随时间增加，并且在植入后一年显示出与天然组织相似的强度，这表明组织在体内随时间再生以产生新的“工程血管”。此外，在植入后6个月，TEVA的壁厚与天然组织的壁厚相似，并且耐受静脉压良好，没有任何问题，如钙化。组织学上，TEVA中的炎性细胞如CD 4阳性或MCP-1阳性细胞随时间减少。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，而没有不希望的副作用。

This study demonstrates the evaluation of the endothelial function and mechanical properties 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(l-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 and observed for 1, 3, 6 and over 12 months.Inner surface of TEVAs (8 mm in diameter and 2 cm in length) were covered with endothelial cells. Histologically, smooth muscle cells, collagen fibers and elastic fibers. which constitute the vessel wall increased gradually with time after implantation. And the specimens after a year after implantation revealed matured vessel-like-structure. The mechanical properties of TEVAs increased with time and showed similar strength as native tissue at a year after implantation, suggesting that the tissue regenerate with time in vivo to create a new "engineered-vessel". Furthermore, wall thicknesses of TEVAs at 6 months after implantation were similar to that of native tissue, and tolerated venous pressure well without any problems such as calcification. Histologically, inflammatory cells such as CD4 positive or MCP-1 positive cells in TEVAs decreased with time. These results indicate that TEVAs are biocompatible material with functional endothelial cells and biomechanical properties without unwanted side-effects.