2. Academic Validation
  3. Optogenetic activation of mechanical nociceptions to enhance implant osseointegration

Optogenetic activation of mechanical nociceptions to enhance implant osseointegration

  • Nat Commun. 2025 Mar 31;16(1):3093. doi: 10.1038/s41467-025-58336-x.
Qijin Wang # 1 2 3,  Yang Chen # 1 2 3,  Haiqi Ding # 1 2 3,  Yuanqing Cai # 1 2 3,  Xuhui Yuan 1 2 3,  Jianhua Lv 1 2 3,  Jiagu Huang 1 2 3,  Jiexin Huang 1 2 3,  Chaofan Zhang 1 2 3,  Zihao Hong 1 2 3,  Hongyan Li 1 2 3,  Ying Huang 1 2 3,  Jiamin Lin 1 2 3,  Lin Yuan 1 2 3,  Lan Lin 1 2 3,  Shaolin Yu 1 2 3,  Canhong Zhang 1 2 3,  Jianhua Lin 1 2 3,  Wenbo Li 1 2 3,  Cheng Chang 4,  Bin Yang 5 6,  Wenming Zhang 7 8 9,  Xinyu Fang 10 11 12
Affiliations

Affiliations

  • 1 Department of Orthopaedic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
  • 2 Department of Orthopedic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
  • 3 Fujian Provincial Institute of Orthopedics, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
  • 4 Institute of New Materials, Guangdong Academy of Sciences, Guangdong-Hong Kong Joint Laboratory of Modern Surface Engineering Technology, Guangdong Provincial Key Laboratory of Modern Surface Engineering Technology, Guangzhou, Guangdong, PR China.
  • 5 Department of Laboratory Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China. yangbin2864@163.com.
  • 6 Department of Laboratory Medicine, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. yangbin2864@163.com.
  • 7 Department of Orthopaedic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. zhangwm0591@fjmu.edu.cn.
  • 8 Department of Orthopedic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China. zhangwm0591@fjmu.edu.cn.
  • 9 Fujian Provincial Institute of Orthopedics, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. zhangwm0591@fjmu.edu.cn.
  • 10 Department of Orthopaedic Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. fangxinyu0417@fjmu.edu.cn.
  • 11 Department of Orthopedic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China. fangxinyu0417@fjmu.edu.cn.
  • 12 Fujian Provincial Institute of Orthopedics, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. fangxinyu0417@fjmu.edu.cn.
  • # Contributed equally.
PMID: 40164597 DOI: 10.1038/s41467-025-58336-x
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.

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