Fabrication Of Small Diameter Vascular Graft Using Stacked Collagen Films

Abstract

Collagen I have been widely used in the field of vascular tissue engineering. They are characterized better for their interaction at the cellular level but are often limited as vascular graft due to their weak mechanical strength and thrombic property. The crosslinking chemicals or polymers support are used to overcome weak mechanical property. Crosslinking agents tend to have cytotoxic effects while blend with synthetic polymers have mismatch or compliancy issues inside the body. Here in this set of study, we used stacked collagen films and embedded drug delivery system within the film to construct small tubular conduits to meet the mechanical demands of a successful vascular graft and overcome thrombic nature of collagen material. Later in the studies we also enforce elastin within the collagen film to shows its efficiency of our fabrication design to tune mechanical property to desirable needs. At the end of studies, fibronectin, heparin and aspirin drug have been blended with tubular construct to improve the hemocompatiblity features. Here we report burst pressure of 4259±733 mmHg and suture retention strength of 293±13 gf of 15 layers collagen tubular construct. We also report burst pressure of 3240±542 mmHg and suture retention strength of 368±40 gf of 10 layers collagen-elastin tubular construct. The burst pressure of both 15 layers collagen and 10 layers collagen-elastin tubular construct was higher than human saphenous veins (4259±733, 3240±542 vs. 1976±419 mmHg) and matched closely with human artery (4259±733, 3240±542 vs. 3128±1551 mmHg). The collagen film supported cell adhesion, differentiation and proliferation well. The collagen tubular construct was successfully coated with fibronectin showing more endothelial cell growth. The toluidine blue staining showed presence of heparin molecules throughout the layer of the tubular structure decreasing the chances of blood clot in vivo studies. Finally aspirin drug was embedded within the tubular structure for local release at the site of surgery to avoid platelet adhesion and reduced blood clot. The spectrophotometer analysis showed the behavior of drug release profile over the period of 5 days. The tunable mechanical property and fabrication method free of crosslinking agents makes this design very appealing for the future of vascular tissue engineering of small diameter vascular grafts.