Heparin loading and pre-endothelialization in enhancing the patency rate of electrospun small-diameter vascular grafts in a canine model

We herein proved that the two commonly used antithrombotic methods, heparin loading and pre-endothelialization could both greatly enhance the patency rate of a small-diameter graft in a canine model. Tubular grafts having an inner diameter of 4 mm were prepared by electrospinning poly(l-lactide-co-ε-caprolactone) (P(LLA-CL)) and heparin through a coaxial electrospinning technique. Seventy-two percent of heparin was found to be released sustainably from the graft within 14 days. To prepare the pre-endothelialized grafts, we seeded endothelial cells isolated from the femoral artery and cultured then dynamically on the lumen until a cell monolayer was formed. Digital subtraction angiography (DSA) and color Doppler flow imaging (CDFI) were used to monitor the patency without sacrificing the animals. Histological analyses revealed that following the direction of blood flow, a cell monolayer was formed at the proximal end of the heparin-loaded grafts, but such a monolayer could be found in the middle or distal region of the grafts. In contrast, the whole luminal surface of the pre-endothelialized graft was covered by a cell monolayer, suggesting the in vivo survival of the preseeded cells. This demonstrated that heparin was a comparatively simple method to achieve good patency, but the pre-endothelialization had better mechanical properties and cellular compatibility.