Abstract
Clinically, a multitude of factors can contribute to the development of bone defects. In the process of bone healing, the nervous system plays a vital role in bone regeneration. Small molecules from the nervous system, such as neurotrophic factors and neuropeptides, have been found to stimulate osteoblast proliferation and differentiation by activating signaling pathways associated with bone calcification and angiogenesis. These small molecules play a crucial regulatory role at various stages of bone healing. The systematic release mechanism of small molecules within the nervous system through diverse bone tissue engineering materials holds significant clinical implications for the controlled regulation of the bone healing process. This review provides an overview of the involvement of various nervous system small molecules at different stages of bone healing and discusses their regulatory mechanisms, aiming to establish a theoretical foundation for programmed regulation in bone regeneration and design of replacement materials in bone tissue engineering.