REDV-modified decellularized microvascular grafts for arterial and venous reconstruction

Abstract

Recently, a decellularized microvascular graft (inner diameter: 0.6 mm) modified with the integrin α4β1 ligand, REDV, was developed to provide an alternative to autologous-vein grafting in reconstructive microsurgery, showing good early-stage patency under arterial flow in rats. This consecutive study evaluated its potential utility not only as an arterial substitute, but also as a venous substitute, using a rat-tail replantation model. Graft remodeling depending on hemodynamic status was also investigated. ACI rat tail arteries were decellularized via ultra-high-hydrostatic pressure treatment and modified with REDV to induce antithrombogenic interfaces and promote endothelialization after implantation. Grafts were implanted into the tail artery and vein to re-establish blood circulation in amputated Lewis rat tails (n = 12). The primary endpoint was the survival of replants. Secondary endpoints were graft patency, remodeling, and regeneration for 6 months. In all but three cases with technical errors or postoperative self-mutilation, tails survived without any evidence of ischemia or congestion. Six-month Kaplan–Meier patency was 100% for tail-artery implanted grafts and 62% for tail-vein implanted grafts. At 6 months, the neo-tunica media (thickness: 95.0 μm in tail-artery implanted grafts, 9.3 μm in tail-vein implanted grafts) was regenerated inside the neo-intima. In conclusion, the microvascular grafts functioned well both as arterial and venous paths of replanted-rat tails, with different remodeling under arterial and venous conditions.