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.