Optogenetic activation of mechanical nociceptions to enhance implant osseointegration

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, Shaolin Yu, Canhong Zhang, Jianhua Lin, Wenbo Li, Cheng Chang, Bin Yang (), Wenming Zhang () and Xinyu Fang ()
Additional contact information
Qijin Wang: Fujian Medical University
Yang Chen: Fujian Medical University
Haiqi Ding: Fujian Medical University
Yuanqing Cai: Fujian Medical University
Xuhui Yuan: Fujian Medical University
Jianhua Lv: Fujian Medical University
Jiagu Huang: Fujian Medical University
Jiexin Huang: Fujian Medical University
Chaofan Zhang: Fujian Medical University
Zihao Hong: Fujian Medical University
Hongyan Li: Fujian Medical University
Ying Huang: Fujian Medical University
Jiamin Lin: Fujian Medical University
Lin Yuan: Fujian Medical University
Lan Lin: Fujian Medical University
Shaolin Yu: Fujian Medical University
Canhong Zhang: Fujian Medical University
Jianhua Lin: Fujian Medical University
Wenbo Li: Fujian Medical University
Cheng Chang: Guangzhou
Bin Yang: The First Affiliated Hospital of Fujian Medical University
Wenming Zhang: Fujian Medical University
Xinyu Fang: Fujian Medical University

Nature Communications, 2025, vol. 16, issue 1, 1-21

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-58336-x

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