Acellular scaffolding for vascular tissue-engineering in a canine model

Abstract

Introduction: We are presently investigating acellular venous tissue as a bioscaffold to be recellularized with the recipient’s own cells prior to implantation. This study tests the biocompatibility and mechanical stability of this construct in terms of graft patency, acute dilatation and rupture, the ability to achieve and maintain hemostasis and resist infection in a canine model. Methods: Twenty-six carotid interposition grafts were constructed using 13 mongrel dogs. Graft material was obtained from the external jugular veins of the same 13 animals (14 autografts, 4 acellular autografts, 4 allografts, and 4 acellular allografts). Decellularization was performed using 0.075% SDS. At two weeks, each graft was evaluated for evidence of gross patency and dilatation, and perfusion fixed for detailed histological and immunohistochemical analyses (H&E, Factor VIII, smooth muscle actin, and inflammatory markers). Morphometric analysis of the cells present in 20 random high-powered fields (hpf) was conducted at the graft’s midpoint. Healing response was further characterized by evaluation of graft incorporation into surrounding tissues and recellularization at the anastamotic sites. Results: All animals survived without neurologic deficit with 100% patency, and no dilatation or rupture. There were no clinically significant infections. The quantified inflammatory reaction was significantly greater in fresh allografts compared to acellular allografts, acellular autografts and fresh autografts: 59 ± 24 vs 19 ± 15, 27 ± 18 or 19 ± 8 cells/hpf, respectively, P < 0.05. There was no significant difference between fresh autografts and acellular allografts, P > 0.05. Fresh autografts also retained endothelial and smooth muscle cells, which were absent in decellularized grafts at implantation and at two weeks. Conclusions: We have previously shown sufficient strength, the ability to support endothelial cells, preserved extracellular collagen and elastin, and reduced allosensitization. Acellular venous scaffolding also appears to avoid acute dilatation or rupture, maintain hemostasis and remain free of infectious complications. It is our hope that this may improve the overall utility and functionality of autologous cell seeding and continue to remodel as the recipient’s new blood vessel in vivo.