Gene-engineered hybrid prostheses for small vascular reconstruction

在小口径动脉重建中，人与人工材料之间的愈合过程困难是人工动脉假体移植失败的主要原因。本课题旨在克服这一问题，建立小口径假肢。为了解决这一难题，我们进行了以下研究：1)建立血管细胞的基因转移方法；2)开发小口径动脉移植物。1)建立血管壁细胞基因转移方法：采用压力法、hvj包膜载体法、超声法三种不同的方法向血管进行基因转移，并评价转移效率和血管壁结构损伤程度。本研究结果表明，hvj包膜法是将基因转移到血管壁细胞的最有效且侵入性较小的方法。2)小口径假体的发展：平滑肌细胞播种杂交人工假体。人类细胞在人工材料上的生长和细胞再生能力远不如其他物种，即使生长因子供应或肝脏生长因子基因转移。抗血栓特性也是小口径人工假体尚未解决的问题。因此，混合人工移植物在犬股动脉重建模型中均被闭塞。另一方面，生物材料如动脉同种异体移植物在抗血栓形成和细胞再生方面具有优越的特性。综上所述，由于人体对人工材料的抵抗力，小口径人工假体的建立仍存在一定的困难。然而，同种异体移植物等生物材料在抗血栓形成和细胞再生方面具有广阔的前景。因此，组织工程化同种异体移植物，如脱细胞同种异体移植物或基因转移同种异体移植物是小口径假肢的下一个目标。少

Difficulty of the healing process between human being and artificial materials is main cause of graft failure of artificial arterial prostheses in small caliber arterial reconstruction. This research project has been perform in order to overcome this problem and establish small caliber prostheses.To resolve this difficult situation, we perform the following research and try to 1)establish of gene transfer methods for vascular cells, 2)developement of small caliber arterial graft.1)Establish of gene transfer methods for vascular wall cells : We perform gene transfer to blood vessel by three different methods including pressure method, HVJ-Envelope vector method, and ultrasonic method, and evaluate the transfer efficiency and degree of structural damage of vessel wall. As the results of this research, the HVJ-Envelope method is most effective and less invasive for gene transfer to vessel wall cells.2)Development of small caliber prostheses : smooth muscle cell seeding hybrid artificial p … More rostheses was evaluated in vitro as well as in vivo. Human cell growth as well as cell repopulation on the artificial material is much inferior compared to other species, even if growth factors supply or hepatic growth factor gene transfer. Anti-thrombotic characteristics is also unsolved problem for small caliber artificial prostheses. Therefore, hybrid artificial grafts were all occluded in canine femoral arterial reconstruction model. On the other hands, biologic materials such as arterial allograft have superior characteristics regarding antithrombogenecity and cell repopulation.In conclusion, it is still difficult to establish small caliber artificial prostheses because of human system against artificial materials. However, the biological materials such as allograft have promising characteristics in terms of anti-thrombogenicity and cell repopulation. So, tissue engineered allograft such as decellularized allograft or gene transferred allograft are next target of small caliber prostheses. Less