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      Engineered Sensory Nerve Guides Self‐Adaptive Bone Healing via NGF‐TrkA Signaling Pathway

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          Abstract

          The 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.

          Abstract

          The adaptation feature of sensory nerve during tissue formation is leveraged to propose a neuromodulation approach to orchestrate bone defect healing by constructing engineered sensory nerves (eSN) in situ. eSN sustained‐release NGF to promote sensory nerve reinnervation, which regulates MSC osteogenic differentiation, vascular regeneration, and regulates osteoblast and osteoclasts to participate in bone remodeling and guides self‐adaptive bone healing.

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          Author and article information

          Contributors
          wuyanzju@zju.edu.cn
          yezhaoming@zju.edu.cn
          xiaohuayu@zju.edu.cn
          Journal
          Adv Sci (Weinh)
          Adv Sci (Weinh)
          10.1002/(ISSN)2198-3844
          ADVS
          Advanced Science
          John Wiley and Sons Inc. (Hoboken )
          2198-3844
          01 February 2023
          April 2023
          : 10
          : 10 ( doiID: 10.1002/advs.v10.10 )
          : 2206155
          Affiliations
          [ 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
          Author notes
          Author information
          https://orcid.org/0000-0002-0233-0121
          Article
          ADVS5141
          10.1002/advs.202206155
          10074090
          36725311
          cffe2498-ae28-4b24-be12-0b4bd7901a2c
          © 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH

          This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

          History
          : 10 January 2023
          : 21 October 2022
          Page count
          Figures: 10, Tables: 0, Pages: 15, Words: 8590
          Funding
          Funded by: National Key Research and Development Projects
          Award ID: 2018YFC1105400
          Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
          Award ID: 81872173
          Award ID: 82072959
          Award ID: 31870959
          Funded by: Natural Science Foundation of Zhejiang province
          Award ID: GF22H068757
          Funded by: Medical and Key R&D Project of Zhejiang Province
          Award ID: 2022C01076
          Funded by: Zhejiang Undergraduate Talent Project
          Award ID: 2020R401218
          Categories
          Research Article
          Research Articles
          Custom metadata
          2.0
          April 5, 2023
          Converter:WILEY_ML3GV2_TO_JATSPMC version:6.2.7 mode:remove_FC converted:05.04.2023

          bmp‐2,extracellular matrix,nerve growth factor,osteogenesis,sensory nerve

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