Optogenetic activation of mechanical nociceptions to enhance implant osseointegration
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<sup>+</sup> 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<sup>+</sup> 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.
Authors
- Xuhui Yuan
- Ying Huang (ORCID: https://orcid.org/0000-0001-9951-6290)
- Canhong Zhang (ORCID: https://orcid.org/0000-0002-3278-1759)
- Wenming Zhang (ORCID: https://orcid.org/0000-0003-1567-7279)
- Q. Wang (ORCID: https://orcid.org/0000-0001-6978-653X)
- Yuanqing Cai (ORCID: https://orcid.org/0000-0001-5364-414X)
- Sun‐Kyoung Yu (ORCID: https://orcid.org/0000-0003-0801-1663)
- Haiqi Ding
- Jianhua Lv (ORCID: https://orcid.org/0009-0003-2706-5613)
- Lan Lin (ORCID: https://orcid.org/0000-0001-7387-2027)
- Xinyu Fang (ORCID: https://orcid.org/0000-0001-6337-8009)
- Yang Chen (ORCID: https://orcid.org/0000-0002-1863-5544)
- Cheng Chang (ORCID: https://orcid.org/0000-0002-0677-0677)
- Hong Zhang (ORCID: https://orcid.org/0000-0002-6191-0046)
- Hongyan Li (ORCID: https://orcid.org/0000-0003-3603-4045)
- Jiamin Lin
- Bin Yang (ORCID: https://orcid.org/0000-0002-5139-5888)
- Jianhua Lin (ORCID: https://orcid.org/0000-0003-0698-0292)
- Yuan Lin (ORCID: https://orcid.org/0000-0002-8275-9306)
- Jiexin Huang (ORCID: https://orcid.org/0009-0009-3356-6418)
- Wenbo Li (ORCID: https://orcid.org/0000-0001-6131-8766)
- Chaofan Zhang (ORCID: https://orcid.org/0000-0001-7397-2298)
- Jiagu Huang (ORCID: https://orcid.org/0009-0006-5487-3212)
Institutions
- Fujian Medical University (CN)
- Guangdong Academy of Sciences (CN)
- First Affiliated Hospital of Fujian Medical University (CN)
- Guangdong Institute of New Materials (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-03-31
- DOI
- https://doi.org/10.1038/s41467-025-58336-x
- Citations
- 15
- Primary Topic
- Photoreceptor and optogenetics research
- Type
- article
- Field-Weighted Citation Impact
- 13.64