Three-dimensional chitosan-PCL biodegradable tissue scaffold and BDNF-enriched Wharton Gel investigation of the effectiveness of mesenchymal stem cell-derived secretome on nerve regeneration in rat sciatic nerve defects of different lengths: An experimental study

Introduction: Peripheral nerve injuries often lead to significant functional deficits, and autografts remain the gold standard for repairing critical-sized nerve defects. However, drawbacks such as donor site morbidity and limited tissue availability have driven the exploration of alternative strategies. Tissue-engineered nerve conduits enriched with biological agents have emerged as a promising approach to support nerve regeneration. Materials-Methods: In this experimental study, biodegradable three-dimensional (3D) nerve conduits composed of polycaprolactone (PCL) and chitosan (75:25 w/w) were fabricated and utilized to repair sciatic nerve defects of two different lengths—10 mm and 15 mm—in 64 Wistar Albino rats (32 rats per defect length). The conduits were applied alone or in combination with secretome derived from Wharton's Jelly mesenchymal stem cells (WJ-MSC), either in its native form or enriched with brain-derived neurotrophic factor (BDNF). Rats were randomly divided into eight groups based on the defect length and treatment: 10 mm groups: Group 1: Autograft Group 2: Conduit only Group 3: Conduit + WJ-MSC secretome Group 4: Conduit + BDNF-enriched secretome 15 mm groups: Group 5: Autograft Group 6: Conduit only Group 7: Conduit + WJ-MSC secretome Group 8: Conduit + BDNF-enriched secretome Functional recovery was evaluated using the Pin Prick Test, Toe Spread Test, Sciatic Functional Index (SFI), electromyography (EMG), and gastrocnemius muscle wet weight. In addition, morphological and histopathological analyses were performed. Results: Group 4 demonstrated statistically similar results to the autograft control groups (Groups 1 and 5) while showing significantly superior functional and electrophysiological outcomes compared to Groups 2, 3, 6, 7, and 8 (p<0.05). Histological analyses revealed enhanced axonal regeneration, reduced inflammation, and improved miyelination in Group 4. Scanning electron microscopy (SEM) confirmed the structural integrity and stability of the conduit throughout the 12-week evaluation period. Conclusion: The combination of BDNF-enriched WJ-MSC-derived secretome with a 3D biodegradable chitosan-PCL nerve conduit effectively supported peripheral nerve regeneration in 10 mm sciatic nerve defects in a rat model. This approach holds significant promise as a potential clinical alternative to autografts in the treatment of critical-sized peripheral nerve injuries.