Conklin B S, Richter E R, Kreutziger K L, Zhong D-S, Chen C
School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30322, USA.
Med Eng Phys. 2002 Apr;24(3):173-83. doi: 10.1016/s1350-4533(02)00010-3.
Although autogenous saphenous vein remains the standard for coronary and infrapopliteal bypass, many patients do not have a suitable vein. Attempts at developing a small-caliber vascular graft have failed largely due to occlusion, neointimal hyperplasia, or aneurismal degradation. We have designed and characterized a novel small-caliber vascular xenograft that may overcome these failure modes. To reduce immune reactions, porcine common carotid arteries were decellularized by enzymatic and detergent treatments. Histology and electron microscopic examination showed complete removal of cellular components while the extracellular matrix structure remained intact. To reduce thrombogeneity, decellularized vascular grafts were covalently linked with heparin. The efficiency of heparin linkage was demonstrated with toluidine blue staining and the antithrombogeneity of the heparin-treated grafts was demonstrated with a clot time test. Mechanical testing of the graft was performed. Decellularized-heparin-treated grafts were similar in compliance to fresh vessels and burst testing showed grafts to withstand pressures exceeding 10 times physiologic blood pressure. There was no difference in suture retention strength between fresh vessels and decellularized-heparin-treated grafts. Decellularized, heparinized grafts were implanted in dogs as carotid artery bypass grafts and showed smooth muscle cells densely populating the wall, and endothelial cells lining the lumen by two months. This study provides a new strategy to develop a small-caliber vascular graft with excellent mechanical properties, antithrombogeneity, and tissue compatibility.
尽管自体大隐静脉仍是冠状动脉旁路移植术和腘以下旁路移植术的金标准，但许多患者并无合适的静脉。开发小口径血管移植物的尝试大多因血管闭塞、新生内膜增生或动脉瘤样退变而失败。我们设计并表征了一种新型小口径血管异种移植物，它可能克服这些失败模式。为减少免疫反应，采用酶法和去污剂处理对猪颈总动脉进行脱细胞处理。组织学和电子显微镜检查显示细胞成分被完全清除，而细胞外基质结构保持完整。为降低血栓形成倾向，将脱细胞血管移植物与肝素共价连接。通过甲苯胺蓝染色证明了肝素连接的效率，并通过凝血时间试验证明了肝素处理移植物的抗血栓形成能力。对移植物进行了力学测试。脱细胞肝素处理的移植物在顺应性方面与新鲜血管相似，爆破试验表明移植物能够承受超过生理血压10倍的压力。新鲜血管与脱细胞肝素处理的移植物在缝线保留强度方面没有差异。将脱细胞、肝素化的移植物作为颈动脉旁路移植物植入犬体内，两个月后可见平滑肌细胞密集地分布在血管壁，内皮细胞覆盖管腔。本研究为开发具有优异力学性能、抗血栓形成能力和组织相容性的小口径血管移植物提供了一种新策略。
