Synergistic Effects of Secretome and Surgical Angiogenesis in Acellular Nerve Allograft-Mediated Peripheral Nerve Repair in a Rat Model.

BACKGROUND

Critical-sized peripheral nerve defects remain a major reconstructive challenge. Although autografts are considered the gold standard, their use is limited by donor-site morbidity and graft availability. Acellular nerve allografts (ANAs) offer a promising alternative but are often hampered by inadequate revascularization and limited functional outcomes in large defects. This study investigates whether combining mesenchymal stem cell-derived secretome therapy with surgical angiogenesis can enhance the regenerative capacity of ANAs.

METHODS

Forty male Wistar rats were randomly assigned to 5 groups (n=8): group 1 (reversed autograft), group 2 (ANA), group 3 (ANA+secretome), group 4 (ANA+surgical angiogenesis), and group 5 (ANA+secretome+surgical angiogenesis). A 10 mm sciatic nerve defect was created in all animals. Functional recovery was evaluated using the Sciatic Functional Index (SFI) at 6 and 9 weeks. Electrophysiological, histologic, immunohistochemical (CD34), and muscle weight/volume assessments were performed at 9 weeks.

RESULTS

Group 5 demonstrated the highest functional recovery among ANA-based interventions, achieving outcomes comparable to autografts. Groups 4 and 5 showed significantly improved axonal regeneration compared with ANA alone. CD34 immunostaining revealed enhanced vascularization in groups 4 and 5, with levels similar to the autograft group. No significant differences were observed in electrophysiological or muscle mass parameters.

CONCLUSIONS

The combination of secretome therapy and surgical angiogenesis synergistically enhances the regenerative performance of acellular nerve allografts. This strategy may provide a clinically translatable alternative to autografts, particularly in challenging repair scenarios involving avascular or scarred recipient beds.