Peripheral Nerve Repair: Historical Perspectives, Current Advances, and Future Directions in Natural and Synthetic Neural Conduits

ABSTRACT Regenerative medicine aims to restore damaged tissues or organs using stem cells, biomaterials, and decellularized grafts. Peripheral nerve injuries (PNI), affecting 2.8% of patients, lead to severe functional impairments with global socioeconomic costs exceeding $7 billion annually. Despite advancements in surgical techniques, full functional recovery remains elusive, particularly in critical gap injuries (> 3 cm). Autografts remain the gold standard but are hindered by donor tissue scarcity and complications like neuroma formation. Allografts face challenges due to the lack of Schwann cells and neurotrophic support. Emerging approaches in tissue engineering leverage synthetic materials, such as polycaprolactone (PCL) and polylactic acid (PLA), and biological scaffolds like decellularized nerve grafts. These innovations provide structural support, promote axonal regeneration, and retain extracellular matrix components, enabling cell adhesion and migration while minimizing antigenicity. However, barriers such as mechanical instability, scar tissue formation, and inadequate cellularization persist. This review explores the anatomy and clinical significance of the sciatic nerve, historical perspectives on peripheral nerve repair, and current treatment strategies. It evaluates biological and synthetic nerve conduits, highlighting FDA‐approved products and their advantages in promoting nerve regeneration. Additionally, the paper discusses challenges in the field, including limited functional recovery and the need for more effective clinical solutions. By combining natural and synthetic materials with growth factor delivery and vascularization strategies, engineered scaffolds hold promise for improving outcomes in PNI repair. Further research is essential to optimize these technologies and bridge existing gaps in clinical practice.