Affiliation:
1. Department of Orthopedic Surgery The Second Affiliated Hospital Zhejiang University School of Medicine Orthopedics Research Institute of Zhejiang University Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province 88 Jiefang Road Hangzhou City Zhejiang Province 310003 P. R. China
2. Department of Orthopedic Taizhou First People's Hospital Wenzhou Medical University 218 Hengjie Road, Huangyan District Taizhou City Zhejiang Province 318020 P. R. China
Abstract
AbstractThe upstream role of sensory innervation during bone homeostasis is widely underestimated in bone repairing strategies. Herein, a neuromodulation approach is proposed to orchestrate bone defect healing by constructing engineered sensory nerves (eSN) in situ to leverage the adaptation feature of SN during tissue formation. NGF liberated from ECM‐constructed eSN effectively promotes sensory neuron differentiation and enhances CGRP secretion, which lead to improved RAOECs mobility and osteogenic differentiation of BMSC. In turn, such eSN effectively drives ossification in vivo via NGF‐TrkA signaling pathway, which substantially accelerates critical size bone defect healing. More importantly, eSN also adaptively suppresses excessive bone formation and promotes bone remodeling by activating osteoclasts via CGRP‐dependent mechanism when combined with BMP‐2 delivery, which ingeniously alleviates side effects of BMP‐2. In sum, this eSN approach offers a valuable avenue to harness the adaptive role of neural system to optimize bone homeostasis under various clinical scenario.
Funder
National Natural Science Foundation of China
Subject
General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)
Cited by
6 articles.
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