Repair Of Rat Sciatic Nerve Defect With Optimized Acellular Nerve

The autologous nerve grafting, which is still the standard method to repair a nerve gap clinically, will be performed after the injury of peripheral nerves if the suture without tensility cannot be achieved. For the reason that there is a lack of nerve autografts and more injuries and new sensory dysfunction are unavoidable when a autologous cutaneous nerve having been harvested, it is essential to develop a new effective nerve graft instead of autografts. The repair by transplantation of fresh nerve allografts and xenografts will be a failure because of the transplant rejection reaction, which can be avoided by removal of cellular materials in the grafts. There are many kinds of ways to obtain acellular nerve, of which the most common ones are thermal and chemical processes. Although thermal decellularization does kill the cells and render the graft generally nonimmunogenic, the process does not extract the cell remnants. Several chemical treatments have been designed to render nerve grafts nonimmunogenic while also removing much of the cellular debris. However, chemical treatments cause more damage to the ECM than thermal decellularization. Hudson, etc. developed a new chemical decellularization process to create optimized acellular (OA) nerve grafts with an extracellular environment similar to that of native nerve tissue, but without the cellular material that is believed to elicit cell-mediated rejection. But their research in vivo is superficial and the functional recovery was not evaluated. For the lack of nerve allografts clinically, the xenogenic nerve grafts are needed, which will not cause ethical problems also. If we find the capacity of xenogenic nerve grafts to repair peripheral nerve defects is similar to those of nerve autografts and allografts, it will be of great clinical importance. So we observed in this research the immune rejection, nerve regeneration and functional recovery of rat sciatic nerve defect bridged by optimized acellular nerve and autologous nerve and compared them to each other.Firstly, we obtained the optimized acellular nerve grafts and performed the transplant operation. The right sciatic nerve of adult Sprague-Dawley(SD) rats were exposed and 1.0cm long segment of the nerves were removed and repaired by optimized acellular rabbit and rat nerve. After 1 month and 3 months respectively, sciatic functional index(SFI), electrophysiological and histological studies were conducted to evaluate immune rejection, nerve regeneration and functional recovery and to compare those parameters in autograft group, allograft group, xenograft group and fresh nerve graft group.1 month after the operation, the results showed that the immune rejection assessed by the levels of CD8+ T cells and macrophages infiltration, nerve regeneration assessed by axon density, and functional recovery evaluated by SFI in the optimized acellular xenograft group was similar to those in the autograft group and allograft group, but significantly better than those in the fresh nerve graft group. 3 months after the operation, the SFI was significantly better, while the others were not. The possible reason for this may be that the new axons had grown completely across the grafts 1 month after the operation. And the new axons had grown to the distal nerve end 3 months after the operation.There are more advantages to repair peripheral nerve defect using natural nerve grafts instead of artificial grafts. And our research proves that the optimized acellular nerve xenografts and allografts are immunologically tolerated. They allow good nerve regeneration and functional recovery and can be potential substitutes for autografts in repairing peripheral nerve defect, especially in repairing extensive or multiple nerve defects or nerve plexus injuries.