Xuyan Wei,1,2 Mucong Li,1,2 Jiaqian You,1,2 Jiaxin Luo,1,2 Jingjie Zhai,1,2 Jiameng Zhang,1,2 Jian Feng,1,2 Hanchi Wang,1,2 Yanmin Zhou1,2 

1Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, 130021, People’s Republic of China; 2Department of Oral Implantology, Hospital of Stomatology, Jilin University, Changchun, 130021, People’s Republic of China

Correspondence: Hanchi Wang; Yanmin Zhou, Department of Oral Implantology, Hospital of Stomatology, Jilin University, Changchun, 130021, People’s Republic of China, Email whc23@jlu.edu.cn; zhouym@jlu.edu.cn

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.

Keywords: nervous system, neurotrophin, neuropeptide, bone healing, procedural controlled release