組織工程之血管移植替代物

Abstract

每年冠狀動脈繞道術(血管直徑＜4 mm)普遍被選用來治療心血管疾病病患，而臨床上大多以自體移植的隱靜脈、合成材料的血管移植替代物或去除細胞的組織(異體、異種移植的臍帶或血管)來做為血管移植替代物。然而，因上述的血管移植替代物有著來源、口徑的限制且容易再次引起血栓及血管再狹窄和嚴重的發炎免疫反應等缺點。為了改善上述這些缺點，本研究乃以組織工程的方式，將豬皮萃取之第一型膠原蛋白當作基材，形成具備適當機械性質特性及良好生物相容性的支架。另外，再接種內皮細胞、平滑肌細胞並以共同培養方式，進而促使血管細胞貼附、增生以及分化，出現類似血管之結構。動物實驗中，血管移植替代物(長約5 mm，內徑約3 mm)皆能成功穩合端部銜接端部(end-to-end anastomoses)接枝於下腔靜脈，不論支架是否有接種細胞，內皮細胞皆能完整鋪列生長於支架上，且皆沒有血栓的形成，但有接種細胞之血管移植替代物，除了形成接觸血液面之內皮細胞層外，並經免疫染色鑑定，於次表面已具有完整環狀之平滑肌細胞的表現，而無接種細胞之血管移植替代物則無平滑肌細胞的出現。相信未來能應用於冠狀動脈繞道移植之小口徑之血管替代物。

In recent decades, cardiovascular disease is becoming the leading cause of death in developed countries only inferior to cancer. Coronary artery bypass graft surgery (for small diameter < 4 mm graft) is performed annually in the world, making it one of the most commonly performed major operations. Autogenous saphenous veins, synthetic grafts, or acellular human umbilical veins are presently used as replacement arteries in surgical procedures. However, limited availability of the graft and the limited conduit diameter troubled clinical doctors. In addition, the recurrences of obstructed blood vessels, thrombosis, and eliciting serious immune response challenged researchers as well. In order to overcome these inconvenience, tissue engineering offers the hope of delivering the replacement function in a much more cost-effective and beneficial way. The objective of this study is to fabricate an adequate blood vessel replacement with suitable mechanical property and biocompatibility for clinical applications. In this study, we are going to prepare blood vessel based on type I collagen by tissue engineering technique. Endothelial cells and smooth muscle cells harvested from endocardium, bladder, and blood vessel will be seeded on a preformed scaffold for cell proliferation and differentiation, and finally developed into a physiologically functional blood vessel. In the animal study, we found that endothelial cells could survive and smoothly cover the whole surface area of the scaffold both in non cell-seeding group and cell-seeding group. However, smooth muscle cells only showed positive reaction by immunostain in the cell-seeding group, but negative reaction in non cell-seeding group. We expect that the tissue-engineering vessel would have the properties of good biocompatibility, anti-thrombosis, resistance to infection, low immunogenicity, and might prevent from platelet aggregation and minimal tissue infiltration.