The objective of our study is to identify new strategies to improve the patency rate of small diameter =< 4mm prosthetic vascular grafts (SDPVG) used in arterial reconstruction. Actually, the use of autologous saphenous vein or internal mammary artery gives a better performance than prosthetic grafts in infrainguinal or coronary position: anyway, these autogenous conduits are diseased or unavailable in about 30% of patients.
Several factors contribute to the determine SDPVGs failure, mainly with a mechanism of thrombotic occlusion or intimal hyperplasia.
No clear benefit has been shown by endothelial cells (EC) seeding of vascular grafts in preventing early graft thrombosis or late graft failure due to intimal hyperplasia.
The concept of our study is to improve SDPVGs patency by seeding the external surface of the graft with genetically modified fibroblasts (to produce the therapeutic agent of choice) or by coating both the luminal and the abluminal surfaces of the graft with biologically active peptides (BAP). More specifically, we use new ex-vivo gene therapy strategies with replication deficient adenovirus vectors and/or graft coating with BAPs to reduce graft failure rate by achieving the following effects a) reduction of SDPVGs surface thrombogenicity; b) inhibition of smooth muscle cell (SMC) proliferation on the luminal surface of the graft; c) inhibition of SMCs and fibroblasts migration from the surrounding tissues into the mesh of the graft.
Moreover, we developed a method for a collagen coating of Dacron grafts. In order to achieve a better surface for cells attachment and also to decrease graft porosity and to improve graft biocompatibility, equine collagen is used to coat the outer surface of the graft.
Grafts treated in one the ways above mentioned are usually tested both in in-vitro flow circuits (with peristaltic pump) and in in-vivo animal models. Animal studies are generally performed in pigs or sheep: grafts are implanted in carotid, aortic or ilio-femoral position and in-vivo assessment of graft behavior is performed using digital subtraction angiography (DSA) and intravascular ultrasound (IVUS).
It is expected that the results of our study will be relevant to better understand the mechanics of graft healing and failure. Moreover, data from experiments will be exploited by graft manufactures for new vascular grafts development and the coating technology will be helpful for those industries dealing with body implants or drug delivery systems to improve the effectiveness of their products.