Senolytics-Integrated GBR Membrane Ameliorates Bone Regeneration by Reversing Cell Senescence
Objectives: In the realm of guided bone regeneration (GBR), elderly patients encounter tougher challenges in the speed and strength of bone regeneration. To bolster the efficacy of GBR in the elderly, the study aims to develop a novel Janus quercetin-loaded and strontium-doped HAp/PLGA (QSHP) GBR membrane to ameliorate aging bone regeneration. Methods: Sr-HAp were synthesized via hydrothermal reaction, followed by the development of QSHP barrier membranes. The morphology and mechanical properties were characterized. The effects on recruiting stem cells, reversing cell senescence, and restoring osteogenic differentiation was assessed through wound healing test, β-gal staining, and ALP staining. Meanwhile, mandibular bone defect models were established in naturally aged rats to evaluate the bone repair efficacy in vivo. Results: The QSHP membrane exhibited distinct characteristics on the two sides, with hydrophobic nature in the PLGA side and released quercetin and Sr2+ in the nanowires side. Moreover, the release of Sr2+ significantly promoted the migration and proliferation of bone marrow mesenchymal stem cells (BMSCs). Besides, the release of quercetin further mitigates cell senescence in BMSCs induced by H2O2, diminishing the secretion of senescent associated secretory phenotype (SASPs) and enhancing the osteogenic differentiation of BMSCs. In vivo experiments confirmed that the QSHP Janus GBR membrane effectively increased the volume of bone regeneration and improve the elastic modulus of the bone tissue at 3 months, greatly ameliorating the strength of aging bone regeneration. Conclusions: The QSHP membrane promotes the regeneration of aging bone by enhancing the recruitment of stem cells and reversing cell senescence caused by oxidative stress, which holds promise for precise therapy in GBR for the elderly population.