Back to Annual Meeting Program

Introduction: Currently there are 15 million diabetic patients in the USA with emerging problem of neuropathy. Many suffer from limb injuries due to sensory function impairment, often involving nerve lesions. Nerve autografting, a golden standard in post-traumatic nerve repair, seems to be an insufficient treatment method for diabetic patients, due to the lack of healthy donor sites and impaired healing of the restored nerve. Therefore there is a need for simple and effective repair method for neuropathic nerve injuries with long defects which are impossible to repair with tension-free simple coaptation.

Purpose: We introduced and investigated peripheral nerve repair using an immunologically inert epineural sheath conduit in diabetic conditions. To evaluate the technique in vivo we used sciatic nerve injury model in diabetic ZDF rats (20mm nerve defects). We used and evaluated isogenic bone marrow stromal cells in enhancement of the regeneration process.

Material and Methods: Fifty-eight Zucker Diabetic Fatty (ZDF) rats were used in the study with inclusion criteria for established diabetes: casual glycemia >200 mg/dl (twice) and post-fasting glycemia >110 mg/dl. A 20mm sciatic nerve defect was created and rats were divided into 4 different nerve repair techniques: Group 1- epineural sheath conduit filled with bone marrow stromal cells (BMSCs, 3-4 x 106 per injection) or saline (Group 2), nerve autograft (Group 3) (n=16 each) and 20mm nerve gap without repair (Group 4, n=10). Sciatic nerve epineural sheath conduit was created by fascicles removal using pull out technique. BMSCs were harvested from the femurs and tibias of the isogenic donors. Epineural sheath conduit or nerve autograft was implanted using microsurgical techniques. Assessments included motor and sensory recovery at 3 weeks intervals. At 6 and 12 weeks follow up somatosensory evoked potentials (SSEP) were recorded and nerve samples were taken for immunohistochemistry and histomorphometric analysis. Muscle denervation atrophy was assessed by Gastrocnemius Muscle Index (GMI) and micromorphometry.

Results: Clinical evaluation, SSEP analysis and nerve and muscle morphometry confirmed significantly better recovery in groups 1 and 2 and the outcomes were comparable to nerve autograft repair. The addition of BMSC contributed to the nerve regeneration in diabetic conditions.

Conclusions: This study confirmed feasibility of application of epineural sheath conduits in restoration of nerve function in diabetic rats. Results comparable with nerve autograft confirmed supportive role of BMSC in diabetic nerve regeneration.