Acellularized Peripheral Nerve Allograft Repopulated with Isogenic Schwann Cells: A Non-Immunogenic Construct that Supports Axonal Growth Across Short Nerve Gaps

Introduction: Reconstructive options for peripheral nerve gaps are currently limited. Autogenous nerve grafts continue to be the gold standard, but are limited by the availability of graft material. All other methods of nerve grafting are either experimental or have limited clinical applicability. We propose developing a tissue engineered peripheral nerve allograft that is non-immunogenic but can support axonal regeneration across peripheral nerve gaps. Methods: The local and systemic immune response to cellular allografts, acellular allografts, and cellular isografts was measured by placing a graft in a subcutaneous tunnel on the dorsal surface of a mouse. Allografts were transplanted across a MHC barrier from Balb C to C57BL6 mice, while isografts were transplanted between C57BL6 mice. The nerve was harvested at either 7 or 21 days, embedded, stained, and the local inflammatory cell infiltrate was quantified. Systemic response was measured at 14 days by quantifying systemic INF, IL-2, IL-4, and IL-5. To evaluate the acellular graft’s ability to support axonal regeneration, and whether reintroducing isogenic Schwann cells (SCs) to the acellular graft improves axonal regeneration, two centimeter gaps in rat peroneal nerve were repaired using an autograft, acellular isograft, or acellular isograft repopulated with isogenic SCs. Force generating capabilities of the rat EDL muscle were evaluated with standard techniques. Results: At 7 and 21 days post transplant, cellular allografts demonstrated a substantial inflammatory cell infiltrate as compared with acellular allografts and isografts. (Table 1)