Self-promoted electroactive biomimetic mineralized scaffolds for bacteria-infected bone regeneration

Zixin Li, Danqing He, Bowen Guo, Zekun Wang, Huajie Yu, Yu Wang, Shanshan Jin, Min Yu, Lisha Zhu, Liyuan Chen, Chengye Ding, Xiaolan Wu, Tianhao Wu, Shiqiang Gong, Jing Mao, Yanheng Zhou, Dan Luo () and Yan Liu ()
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Zixin Li: Peking University School and Hospital of Stomatology
Danqing He: Peking University School and Hospital of Stomatology
Bowen Guo: Chinese Academy of Sciences
Zekun Wang: Chinese Academy of Sciences
Huajie Yu: Peking University School and Hospital of Stomatology
Yu Wang: Peking University School and Hospital of Stomatology
Shanshan Jin: Peking University School and Hospital of Stomatology
Min Yu: Peking University School and Hospital of Stomatology
Lisha Zhu: Peking University School and Hospital of Stomatology
Liyuan Chen: Peking University School and Hospital of Stomatology
Chengye Ding: Peking University School and Hospital of Stomatology
Xiaolan Wu: Peking University School and Hospital of Stomatology
Tianhao Wu: Peking University School and Hospital of Stomatology
Shiqiang Gong: Huazhong University of Science and Technology
Jing Mao: Huazhong University of Science and Technology
Yanheng Zhou: Peking University School and Hospital of Stomatology
Dan Luo: Chinese Academy of Sciences
Yan Liu: Peking University School and Hospital of Stomatology

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Infected bone defects are a major challenge in orthopedic treatment. Native bone tissue possesses an endogenous electroactive interface that induces stem cell differentiation and inhibits bacterial adhesion and activity. However, traditional bone substitutes have difficulty in reconstructing the electrical environment of bone. In this study, we develop a self-promoted electroactive mineralized scaffold (sp-EMS) that generates weak currents via spontaneous electrochemical reactions to activate voltage-gated Ca2+ channels, enhance adenosine triphosphate-induced actin remodeling, and ultimately achieve osteogenic differentiation of mesenchymal stem cells by activating the BMP2/Smad5 pathway. Furthermore, we show that the electroactive interface provided by the sp-EMS inhibits bacterial adhesion and activity via electrochemical products and concomitantly generated reactive oxygen species. We find that the osteogenic and antibacterial dual functions of the sp-EMS depend on its self-promoting electrical stimulation. We demonstrate that in vivo, the sp-EMS achieves complete or nearly complete in situ infected bone healing, from a rat calvarial defect model with single bacterial infection, to a rabbit open alveolar bone defect model and a beagle dog vertical bone defect model with the complex oral bacterial microenvironment. This translational study demonstrates that the electroactive bone graft presents a promising therapeutic platform for complex defect repair.

Date: 2023
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DOI: 10.1038/s41467-023-42598-4

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