The skeleton is a highly innervated organ in which nerve fibers interact with various skeletal cells. Peripheral nerve endings release neurogenic factors and sense skeletal signals, which mediate bone metabolism and skeletal pain. In recent years, bone tissue engineering has increasingly focused on the effects of the nervous system on bone regeneration. Simultaneous regeneration of bone and nerves through the use of materials or by the enhancement of endogenous neurogenic repair signals has been proven to promote functional bone regeneration. Additionally, emerging information on the mechanisms of skeletal interoception and the central nervous system regulation of bone homeostasis provide an opportunity for advancing biomaterials. However, comprehensive reviews of this topic are lacking. Therefore, this review provides an overview of the relationship between nerves and bone regeneration, focusing on tissue engineering applications. We discuss novel regulatory mechanisms and explore innovative approaches based on nerve–bone interactions for bone regeneration. Finally, the challenges and future prospects of this field are briefly discussed.

骨骼是一个高度神经支配的器官，其中神经纤维与各种骨骼细胞相互作用。周围神经末梢释放神经源性因子并感知骨骼信号，从而介导骨代谢和骨骼疼痛。近年来，骨组织工程越来越关注神经系统对骨再生的影响。通过使用材料或通过增强内源性神经源性修复信号来同时再生骨骼和神经已被证明可以促进功能性骨骼再生。此外，有关骨骼内感受机制和中枢神经系统骨稳态调节的新信息为推进生物材料提供了机会。然而，缺乏对该主题的全面评论。因此，本综述概述了神经与骨再生之间的关系，重点关注组织工程应用。我们讨论新的调控机制，并探索基于神经-骨相互作用的骨再生创新方法。最后，简要讨论了该领域的挑战和未来前景。