Peripheral nerve reconstruction. Studies on cellular and acellular iso-, allo- and xenografts

Sammanfattning: The best results after a nerve injury with a defect are achieved by a nerve reconstruction procedure using autologous nerve grafts. However, limitations include insufficient amount of suitable donor material and donor site morbidity. The aim of the present thesis was to study alternative nerve grafts, i.e. allo- and xenografts, in rats and mice. Cellular grafts will evoke a rejection in the host aiming at destroying the graft. Thus, different strategies to suppress or avoid rejection were studied. Treatment with the immunosuppressant FK506 increased axonal outgrowth after a nerve crush lesion, but did not improve axonal outgrowth in autologous nerve grafts in rats. The new strategy of costimulation blockade that inhibits T-cell activation prohibited rejection of nerve allografts in mice in the short term. Rejection of grafts in placebo-treated mice impeded axonal out- growth. In the long-term, costimulation blockade inhibited rejection and resulted in an improved myelination of regenerated axons. A higher target muscle weight indicated less denervation atrophy and thus improved nerve regeneration after costimulation blockade. To avoid immunosuppression altogether acellular nerve allo- and xenografts were studied. The best axonal outgrowth was observed in allografts. The axonal outgrowth in xenografts was influenced by the combination of host/donor species. In conclusion, costimulation blockade inhibits rejection of nerve allografts and allows axonal outgrowth. However, for reconstruction of an isolated severe nerve injury with a defect, the use of acellular nerve allografts is a promising strategy. It addresses many of the limitations of autologous nerve grafts without necessitating immunosuppression.