Favorable Effect Of Chitosan Sustained-release FK506 Incorporated Conduits On Axonal Regeneration In Rat Sciatic Nerve

Background: Peripheral nerve injury is common and serious in clinically. According to the nerve regeneration theory of nerve tropism, neural regeneration room became hot spot for treating nerve injury.Then keep distance between the proximal and distal severed stumps with different conduits and others substance which can promote nerve regeneration ,the room can provid a favourable environment for nerve regeneration. a series of empirical study indicated immunosuppressant FK506 can promote nerve regeneration, chitosan is polysaccharose natural biomaterial , Chitosan is prepared by the N-deacetylation of chitin. chitosan possesses many useful biological properties such as biocompatibility, biodegradation, porosity and mechanical strength, delayed release conduit with favourable nerve Affinity and mechanical function can be made by Chitosan.Objective: To investigate the efficacy of 3 mm gap bridging repairing neurotmesis with chitosan sustained-release FK506 incorporated conduit. We can look forward to searching for a new way in treatment of peripheral nerve injury.Methods: Forty-five adult female wister rats were divided randomly into 3 groups. The rats were received a neurotomy to bilateral sciatic nerve and subsequently reconnected with regeneration chambers. The bridging conduits of group A, B and C were made of silicon tube, chitosan and chitosan sustained-release FK506 incorporated respectively. Conduits absorption and surrounding tissue cicatrization were observed at 1,2,4 weeks after neurotomy. And the nerve regeneration and functional recovery were evaluated by electrophysiology, histological changes, morphometric analysis, and weighing of gastrocnemius muscles at 6, 8 weeks afterneurotomy.Results: All the lower limbs of rats were paralyzed after operation , there were different dermal ulcer at the ankles of the rats. The dermal ulcer of the rats were serious in group B and A more than in group C. The lower limbs of rats revived some autonomic activities in group C at 6 weeks; The lower limbs of rats revived more autonomic activities in group C at 8 weeks; but some rats had the dermal ulcer at the ankles in group B and A at 8 weeks, The lower limbs of rats revived lightly autonomic activities. The silicon tubes of group A adhered severely with surrounding tissue. Bridging grafts of group B and C adhered relatively slightly and could be stripped easily from surrounding tissue .The continuity of sciatic nerve was not established at 1 week. The continuity of sciatic nerve was established at 2 weeks. The diameter of the regeneration nerve were more bigger than 2 weeks at 4 weeks .The regeneration chambers still existed fully at 6 weeks and began to be degradated at 8 weeks after neurotomy. The continuity of sciatic nerve was established without obvious adhesion with surrounding tissue at 8 weeks. The statistical evaluation for nerve regeneration demonstrated that rats of group C showed the best results(P<0.05). Although rats of group B and A were found to be the second and the third respectively, there is no significant difference between them(P>0.05).Conclusion :(1)We have made the chitosan Sustained-release FK506 incorporated conduits.which stabilize for more than 2 months before degradation in vivo .(2)Remaining 3 mm gap bridging repairing rat sciatic nerve with chitosan Sustained-release FK506 incorporated conduits can significantly promote nerve regeneration and facilitate function recovery .