Directed rescue strategy for enhanced implant osteointegration in aged rats

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.

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Publication Details

Journal
Nature Communications
Published
2025-11-24
DOI
https://doi.org/10.1038/s41467-025-65284-z
Primary Topic
Hydrogels: synthesis, properties, applications
Type
article
Field-Weighted Citation Impact
0.00

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article

Directed rescue strategy for enhanced implant osteointegration in aged rats

Xinxin Luo, Jing Wu, Bailong Tao, Kaiyong Cai et al.
Nature Communications
Hydrogels: synthesis, properties, applications
article

Directed rescue strategy for enhanced implant osteointegration in aged rats

Xinxin Luo, Jing Wu, Bailong Tao, Kaiyong Cai, Xiaohua Jiang, Kangkang Zha, Qian Huang, Xuan Li, Ye He, Hao Xiong, Peng Liu, Kai Li, Kun Xu
article en

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.

Nature CommunicationsVol. 16(1)
Guangxi Medical University (CN), Duke University (US), Ministry of Education (TH), Wuhan Union Hospital (CN), The Affiliated Yongchuan Hospital of Chongqing Medical University (CN), Union Hospital (CN), Chongqing Medical University (CN)
National Natural Science Foundation of China, Chongqing University, Natural Science Foundation of Chongqing
Openalex Percentile: Top 69%
Hydrogels: synthesis, properties, applications
DOIOpen Access PDFOpenAlex
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