*Purpose: Vascularized composite allotransplantation (VCA) is a valid therapeutic option for patients with non-salvageable injuries such as severe burns or limb amputation. The immune response that occurs in VCA is not fully understood and is expected to be complex due to a number of opposing immune conditions inherent in the allograft. Furthermore, poor nerve regeneration poses an important challenge in post-operation functional restoration. Rodent models of limb transplantation are critical to study immunological elements of VCA and its subsequent functional rehabilitation. The aim of this study is to determine the functional characteristics of hind-limb transplants in a rat hind limb transplantation model.

*Methods: Orthotopic Hind-limb grafts from either Lewis rats (syngeneic) or ACI rats (allogeneic) were transplanted onto Lewis rats. The recipients were monitored longitudinally for survival and functional recovery. The sensory function of the transplanted limb graft was determined by Hargreaves test, while the locomotor function of the graft was assessed by the DigiGait Imaging System. To test the impact of clinically relevant immunosuppression on the graft function, a group of recipients was treated with Tacrolimus (TAC, 3mg/kg, SC), daily for two weeks.

*Results: All syngeneic grafts survived more than 180 days (the endpoint) with both sensory and locomotor function recovery as early as 30 days post-transplant. Sensory function was totally recovered at 90 days post-transplant, while locomotor function only recovered at most 85% (ensemble paw area measured via DigiGait Imaging System). Allografts developed severe rejection within ten days manifested by skin discoloration followed by necrosis and no functional recovery. TAC significantly prolonged limb graft survival to more than 30 days (31-57 days, n=7) and partially regained their sensory and locomotor functions.

*Conclusions: Using Hargreaves test (sensory) and DigiGait Imaging System (locomotor), functional recovery can hindlimb for both syngeneic and allograft limb transplants. The findings from this study are of value for potential therapeutic approaches to prolong VCA survival and promote nerve regeneration and functional recovery of hind-limb transplants.

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