Peripheral nerve regeneration: Sensory and motor neurons and tissue engineering repair strategies

The functional reconstruction bottleneck induced by peripheral nerve injury essentially arises from a spatiotemporal mismatch between the regenerative dynamics of injured neurons and tissue remodeling. Longsegment nerve defects represent the most intractable clinical scenario, where the approximately 1 mm daily axonal regeneration rate cannot counteract rapid, irreversible skeletal muscle denervation atrophy, frequently resulting in permanent motor deficits even after anatomical nerve reconnection. Autologous nerve transplantation, regarded as the clinical gold standard for longgap repair, is limited by donor tissue scarcity and donorsite morbidity, which further drives the development of alternative tissueengineering strategies. Although tissue-engineered nerve grafts have advanced from simple physical bridging in animal models to the reconstruction of biomimetic microenvironments, their clinical performance in motor function restoration remains suboptimal. This review systematically elaborates the distinct response patterns of sensory neurons and motor neurons throughout the entire process of nerve injury and regeneration, with in-depth analysis of their asymmetric regulatory characteristics within the central-peripheral neural network. Sensory neurons exhibit robust cellautonomous regenerative competence, whereas motor neuron regeneration strongly depends on retrograde trophic feedback from skeletal muscle and suffers progressive regenerative decay under prolonged denervation. Notably, considerable knowledge gaps still exist regarding subtypespecific transcriptional reprogramming of motor neurons, restricting precise motorfunction repair. Furthermore, we summarize state-of-the-art tissue-engineered nerve graft strategies, contrasting microenvironmental remodeling with subtype-targeted therapies. Finally, we propose an innovative framework for next-generation tissue-engineered nerve grafts: evolving from physical bridges into central-peripheral signal relay stations capable of remotely modulating somatic transcriptional programs to achieve synchronized sensory and motor functional recovery. Collectively, this work provides solid theoretical support and a biomimetic design paradigm for the synchronized and efficient reconstruction of both sensory and motor functions following peripheral nerve injury.