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Optogenetic activation of mechanical nociceptions to enhance implant osseointegration

Author

Listed:
  • Qijin Wang

    (Fujian Medical University
    The First Affiliated Hospital of Fujian Medical University
    Fujian Medical University)

  • Yang Chen

    (Fujian Medical University
    The First Affiliated Hospital of Fujian Medical University
    Fujian Medical University)

  • Haiqi Ding

    (Fujian Medical University
    The First Affiliated Hospital of Fujian Medical University
    Fujian Medical University)

  • Yuanqing Cai

    (Fujian Medical University
    The First Affiliated Hospital of Fujian Medical University
    Fujian Medical University)

  • Xuhui Yuan

    (Fujian Medical University
    The First Affiliated Hospital of Fujian Medical University
    Fujian Medical University)

  • Jianhua Lv

    (Fujian Medical University
    The First Affiliated Hospital of Fujian Medical University
    Fujian Medical University)

  • Jiagu Huang

    (Fujian Medical University
    The First Affiliated Hospital of Fujian Medical University
    Fujian Medical University)

  • Jiexin Huang

    (Fujian Medical University
    The First Affiliated Hospital of Fujian Medical University
    Fujian Medical University)

  • Chaofan Zhang

    (Fujian Medical University
    The First Affiliated Hospital of Fujian Medical University
    Fujian Medical University)

  • Zihao Hong

    (Fujian Medical University
    The First Affiliated Hospital of Fujian Medical University
    Fujian Medical University)

  • Hongyan Li

    (Fujian Medical University
    The First Affiliated Hospital of Fujian Medical University
    Fujian Medical University)

  • Ying Huang

    (Fujian Medical University
    The First Affiliated Hospital of Fujian Medical University
    Fujian Medical University)

  • Jiamin Lin

    (Fujian Medical University
    The First Affiliated Hospital of Fujian Medical University
    Fujian Medical University)

  • Lin Yuan

    (Fujian Medical University
    The First Affiliated Hospital of Fujian Medical University
    Fujian Medical University)

  • Lan Lin

    (Fujian Medical University
    The First Affiliated Hospital of Fujian Medical University
    Fujian Medical University)

  • Shaolin Yu

    (Fujian Medical University
    The First Affiliated Hospital of Fujian Medical University
    Fujian Medical University)

  • Canhong Zhang

    (Fujian Medical University
    The First Affiliated Hospital of Fujian Medical University
    Fujian Medical University)

  • Jianhua Lin

    (Fujian Medical University
    The First Affiliated Hospital of Fujian Medical University
    Fujian Medical University)

  • Wenbo Li

    (Fujian Medical University
    The First Affiliated Hospital of Fujian Medical University
    Fujian Medical University)

  • Cheng Chang

    (Guangzhou)

  • Bin Yang

    (The First Affiliated Hospital of Fujian Medical University
    Fujian Medical University)

  • Wenming Zhang

    (Fujian Medical University
    The First Affiliated Hospital of Fujian Medical University
    Fujian Medical University)

  • Xinyu Fang

    (Fujian Medical University
    The First Affiliated Hospital of Fujian Medical University
    Fujian Medical University)

Abstract

Orthopedic implants with high elastic modulus often suffer from poor osseointegration due to stress shielding, a phenomenon that suppresses the expression of intracellular mechanotransduction molecules (IMM) such as focal adhesion kinase (FAK). We find that reduced FAK expression under stress shielding is also mediated by decreased calcitonin gene-related peptide (CGRP) released from Piezo2+ mechanosensitive nerves surrounding the implant. To activate these nerves minimally invasively, we develop a fully implantable, wirelessly rechargeable optogenetic device. In mice engineered to express light-sensitive channels in Piezo2+ neurons, targeted stimulation of the L2-3 dorsal root ganglia (DRG) enhances localized CGRP release near the implant. This CGRP elevation activates the Protein Kinase A (PKA)/FAK signaling pathway in bone marrow mesenchymal stem cells (BMSCs), thereby enhancing osteogenesis and improving osseointegration. Here we show that bioelectronic modulation of mechanosensitive nerves offers a strategy to address implant failure, bridging neuroregulation and bone bioengineering.

Suggested Citation

  • Qijin Wang & Yang Chen & Haiqi Ding & Yuanqing Cai & Xuhui Yuan & Jianhua Lv & Jiagu Huang & Jiexin Huang & Chaofan Zhang & Zihao Hong & Hongyan Li & Ying Huang & Jiamin Lin & Lin Yuan & Lan Lin & Sha, 2025. "Optogenetic activation of mechanical nociceptions to enhance implant osseointegration," Nature Communications, Nature, vol. 16(1), pages 1-21, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58336-x
    DOI: 10.1038/s41467-025-58336-x
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    References listed on IDEAS

    as
    1. Aaron D. Mickle & Sang Min Won & Kyung Nim Noh & Jangyeol Yoon & Kathleen W. Meacham & Yeguang Xue & Lisa A. McIlvried & Bryan A. Copits & Vijay K. Samineni & Kaitlyn E. Crawford & Do Hoon Kim & Paulo, 2019. "A wireless closed-loop system for optogenetic peripheral neuromodulation," Nature, Nature, vol. 565(7739), pages 361-365, January.
    2. Tadatoshi Sato & Shiv Verma & Christian D. Castro Andrade & Maureen Omeara & Nia Campbell & Jialiang S. Wang & Murat Cetinbas & Audrey Lang & Brandon J. Ausk & Daniel J. Brooks & Ruslan I. Sadreyev & , 2020. "A FAK/HDAC5 signaling axis controls osteocyte mechanotransduction," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    3. Alia M. Obeidat & Matthew J. Wood & Natalie S. Adamczyk & Shingo Ishihara & Jun Li & Lai Wang & Dongjun Ren & David A. Bennett & Richard J. Miller & Anne-Marie Malfait & Rachel E. Miller, 2023. "Piezo2 expressing nociceptors mediate mechanical sensitization in experimental osteoarthritis," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
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