van der Bas J M Annemieke, Quax Paul H A, van den Berg Arjen C, van Hinsbergh Victor W M, van Bockel J Hajo
Gaubius Laboratory TNO-PG, Leiden University Medical Center, 2300 RA Leiden, The Netherlands.
J Vasc Surg. 2002 Dec;36(6):1237-47. doi: 10.1067/mva.2002.128932.
One of the most life-threatening vascular diseases is rupture of an abdominal aneurysm. The conventional treatment is based on surgical reconstruction. An alternative treatment is endovascular aneurysm repair (EVAR). Despite many advantages, one of the problems of EVAR is endoleakage from deficient healing between the aortic neck and the fabric of the endograft. We hypothesize that better healing, achieved with induction of vascular cell ingrowth into the graft material, would lead to better graft healing.
Both pig aorta and human normal and aneurysmal aortic wall were used for organ cultures. Various growth factors were evaluated for the potential to induce intimal hyperplasia (ie, platelet-derived growth factor, vascular endothelial growth factor, and basic fibroblast growth factor [bFGF]). After the most potent growth factor had been selected, a vascular prosthetic material (Dacron fabric) impregnated with collagen and heparin was incubated with this growth factor. Impregnated pieces of Dacron were fixated on top of the aortic organ cultures for study of ingrowth of the neointima formation into the graft material.
bFGF was the most potent growth factor to induce neointima in aortic organ cultures. The pieces of impregnated Dacron had a release of 5 ng/24 h of bFGF for a period of at least 28 days. With fixation on top of the aortic organ cultures, the impregnated Dacron was capable of inducing neointima formation and ingrowth of the neointima into the graft material after 28 days.
We showed that a Dacron prosthesis impregnated with collagen, heparin, and bFGF is capable of inducing graft healing in our in vitro model, the aortic organ cultures of pig and human aortas. These results suggest that the problem of endoleakage with EVAR may be solved with a perfect proximal healing between the aortic wall and the prosthesis.
腹主动脉瘤破裂是最危及生命的血管疾病之一。传统治疗方法是手术重建。另一种治疗方法是血管内动脉瘤修复术（EVAR）。尽管有许多优点，但EVAR的问题之一是主动脉颈部与血管内移植物织物之间愈合不良导致的内漏。我们假设，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，将导致更好的移植物愈合。
猪主动脉以及人类正常和动脉瘤性主动脉壁均用于器官培养。评估了各种生长因子诱导内膜增生的潜力（即血小板衍生生长因子、血管内皮生长因子和碱性成纤维细胞生长因子[bFGF]）。在选择了最有效的生长因子后，将浸渍有胶原蛋白和肝素的血管假体材料（涤纶织物）与该生长因子一起孵育。将浸渍的涤纶片固定在主动脉器官培养物上方，以研究新生内膜向内生长到移植物材料中的情况。
bFGF是在主动脉器官培养中诱导新生内膜最有效的生长因子。浸渍的涤纶片在至少28天的时间内bFGF释放量为5 ng/24 h。固定在主动脉器官培养物上方后，浸渍的涤纶在28天后能够诱导新生内膜形成并使新生内膜向内生长到移植物材料中。
我们表明，在我们的体外模型（猪和人类主动脉的主动脉器官培养）中，浸渍有胶原蛋白、肝素和bFGF的涤纶假体能够诱导移植物愈合。这些结果表明，EVAR的内漏问题可能通过主动脉壁与假体之间完美的近端愈合来解决。
