van der Bas J M Annemieke, Quax Paul H A, van den Berg Arjen C, Visser Michel J T, van der Linden Edwin, van Bockel J Hajo
Gaubius Laboratory TNO-PG, Leiden University Medical Center, The Netherlands.
J Vasc Surg. 2004 Apr;39(4):850-8. doi: 10.1016/j.jvs.2003.11.045.
Endovascular aneurysm repair is an alternative treatment of abdominal aortic aneurysm. The procedure is less invasive, and morbidity and most probably mortality are reduced. However, some problems, such as endoleakage, are yet to be resolved. Endoleakage can occur after graft migration, as a result of insufficient fixation of the stent graft. One cause is deficient healing between the aortic neck and the stent graft. We hypothesize that better healing, achieved by induction of vascular cell ingrowth into the graft material, results in better graft fixation. Previously we demonstrated ingrowth of neointima into the graft material if the stent graft is impregnated with a coat of basic fibroblast growth factor (bFGF), heparin, and collagen. In this study we evaluated healing with bFGF-heparin-collagen-coated stent grafts in vivo.
In 4 pigs, 32 endovascular stent grafts, manufactured from standard Dacron and Gianturco Z-stents, were placed in the aorta. The stent grafts were impregnated with either bFGF-heparin containing collagen (n=16) or control collagen (n=16). After 4 and 8 weeks animals were killed, and ingrowth and healing of the stent grafts were macroscopically and electron microscopically evaluated.
After 8 weeks all bFGF-impregnated stent grafts demonstrated ingrowth of tissue and healing between the graft and the aorta, whereas the control nonimpregnated stent grafts showed no ingrowth. Microscopic evaluation demonstrated alpha-smooth muscle actin-positive cells, most probably smooth muscle cells or myofibroblasts, growing from the vascular wall through the graft material.
A Dacron prosthesis impregnated with collagen, heparin, and bFGF induced graft healing in an in vivo pig model, in contrast to nonimpregnated stent grafts. This in vivo study confirms our previous findings in vitro. These results indicate that healing between Dacron and the aorta can be achieved, and suggest that type I endoleakage may be resolved by inducing healing between the aortic wall and the prosthesis with graft material containing growth factor.
血管内动脉瘤修复术是腹主动脉瘤的一种替代治疗方法。该手术侵入性较小，发病率以及很可能死亡率都有所降低。然而，一些问题，如内漏，仍有待解决。支架移植物固定不充分可能导致移植物移位后发生内漏。一个原因是主动脉颈部与支架移植物之间愈合不足。我们推测，通过诱导血管细胞向内生长到移植物材料中实现更好的愈合，会导致更好的移植物固定。此前我们证明，如果支架移植物用碱性成纤维细胞生长因子（bFGF）、肝素和胶原蛋白涂层浸渍，新生内膜会向内生长到移植物材料中。在本研究中，我们评估了bFGF - 肝素 - 胶原蛋白涂层支架移植物在体内的愈合情况。
在4头猪中，将32个由标准涤纶和朱安图科Z型支架制成的血管内支架移植物置于主动脉中。支架移植物用含胶原蛋白的bFGF - 肝素（n = 16）或对照胶原蛋白（n = 16）浸渍。4周和8周后处死动物，通过宏观和电子显微镜评估支架移植物的向内生长和愈合情况。
8周后，所有浸渍bFGF的支架移植物均显示组织向内生长以及移植物与主动脉之间的愈合，而对照未浸渍的支架移植物未显示向内生长。显微镜评估显示α - 平滑肌肌动蛋白阳性细胞，很可能是平滑肌细胞或肌成纤维细胞，从血管壁穿过移植物材料生长。
与未浸渍的支架移植物相比，浸渍有胶原蛋白、肝素和bFGF的涤纶假体在体内猪模型中诱导了移植物愈合。这项体内研究证实了我们之前的体外研究结果。这些结果表明涤纶与主动脉之间可以实现愈合，并表明通过用含生长因子的移植物材料诱导主动脉壁与假体之间的愈合，可能解决I型内漏问题。
