Directed rescue strategy for enhanced implant osteointegration in aged rats

Xuan Li, Xiao Jiang, Ye He, Hongwei Xiong, Qian Huang, Kun Xu, Xin-Xin Luo, Kai Li, Bailong Tao, Kangkang Zha, Jing Wu, Peng Liu and Kaiyong Cai ()
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Xuan Li: Chongqing University, Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering
Xiao Jiang: Chongqing University, Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering
Ye He: Duke University, Thomas Lord Department of Mechanical Engineering and Materials Science
Hongwei Xiong: Chongqing University, Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering
Qian Huang: Chongqing University, Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering
Kun Xu: Chongqing University, Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering
Xin-Xin Luo: Chongqing University, Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering
Kai Li: The First Affiliated Hospital of Chongqing Medical University, Laboratory Research Center
Bailong Tao: The First Affiliated Hospital of Chongqing Medical University, Laboratory Research Center
Kangkang Zha: Huazhong University of Science and Technology, Department of Orthopedics, Union Hospital, Tongji Medical College
Jing Wu: Chongqing University, Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering
Peng Liu: Chongqing University, Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering
Kaiyong Cai: Chongqing University, Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract The elimination of senescent cells can enhance the osteointegration of implants in elderly patients. However, achieving specific clearance of senescent cells without adversely affecting the function of normal cells remains challenging. Here we show an implant surface modification technique to achieve specific clearance of locally senescent cells by modulating their metabolism. Our method involve modifying implants with BPTES, a glutaminase 1 (GLS1) inhibitor, through π-π stacking with dopamine. This modification effectively induces intracellular acidosis in senescent mesenchymal stem cells (MSCs) through suppression of glutaminolysis. Simultaneously, poly(γ-glutamate) (PGA), modified by a layer-by-layer method, serve as a high-density carbon source coating, continuously supporting glutamine metabolism in MSCs without ammonia production. Our results show that modified implants significantly reduce the senescence level around implants and promote osteointegration in aged rats. These findings provide promising insights into the design and application of orthopedic implants for elderly patients.

Date: 2025
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DOI: 10.1038/s41467-025-65284-z

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