Revascularization of tissue-engineered nerve grafts and invasion of macrophages

Nonneural derived nerve conduits fail to support regeneration over larger gaps due to lacking viable Schwann cells. Thus, tissue engineering of nerves is focusing on implantation of viable Schwann cells into suitable scaffolds. We established grafts made from acellular muscles and veins, respectively, seeded with cultured Schwann cells. As timing of revascularization is crucial to determine Schwann cell survival and depending axonal regeneration we studied establishment of vascular architecture in a rat sciatic nerve model (2-cm gap) after 3, 5, 7, and 10 days postoperatively, using albumin bound Evans blue. Additionally, macrophage recruitment was immunohistochemically assessed. Engineered grafts showed a delayed revascularization, starting between day 5 and 7 in comparison to normal autografts, that revascularized by day 3. Macrophage recruitment in autologous nerve grafts was evident by day 3. The engineered groups revealed no macrophage invasion until day 7. As Schwann cells survive up to 7 days in autologous grafts without blood supply, depending purely on diffusion, establishment of vascular structure between day 5 and 7 is rapid enough to support Schwann cell survival in engineered grafts. As these grafts are lacking Wallerian degeneration delayed macrophage invasion may not impair degeneration-dependent regeneration, but presence of macrophage derived or induced growth factors may be decreased.