Heparin Coating of Small‐Caliber Decellularized Xenografts Reduces Macrophage Infiltration and Intimal Hyperplasia

Abstract

Small-caliber decellularized xenografts with surface heparin coating are known to reduce in vivo thrombogenicity. This study was performed to examine whether heparin coating on the small-caliber decellularized xenografts would reduce macrophage infiltration and intimal hyperplasia. In a rabbit model of bilateral carotid implantation, each of the animals (n = 18) received a heparin-coated decellularized xenograft from a canine carotid artery on one side and a nonheparin-coated one on the other side. These experiments were terminated respectively at 1 week (n = 6), 3 weeks (n = 6), and 12 weeks (n = 6). Results showed that, compared with the nonheparin-coated grafts, the heparin-coated grafts had significantly less macrophage infiltration 1 week after implantation, identified by the mouse antirabbit macrophage antibody (RAM11)-positive cells on the vascular wall, covering all the proximal, middle, and distal parts of the grafts (P < 0.01). Moreover, the heparin-coated grafts also showed less deposition of proliferation cell nuclear antigen (PCNA)-positive cells on the vascular wall, indicating less cell proliferation, which was significant not only at 1 week (P < 0.01) but also at 12 weeks (P < 0.01). Intimal hyperplasia, measured by the intimal : media (I : M) ratio, was found similar in both groups at 1 and 3 weeks. However, the I : M ratio was significantly lower in the heparin-coated group than in the nonheparin-coated group at 12 weeks, especially in the proximal anastomosis area (0.76 +/- 0.12 vs. 0.345 +/- 0.06, P < 0.01). Heparin coating of small-caliber decellularized xenografts is associated with an early reduction of macrophage infiltration and intimal hyperplasia in a rabbit model of bilateral carotid artery implantation for 12 weeks. Thus, heparin coating appears to deliver not only the antithrombogeneity but also the antiproliferative property for small-caliber decellularized xenografts.