Ceramic-based biomaterials: Combining regeneration with anti-senescence

The global aging crisis presents significant challenges in treating age-related skeletal disorders, characterized by impaired bone regeneration due to senescent microenvironment dysfunction. While anti-senescence drugs have shown promising therapeutic potential, their clinical use is hindered by severe side effects and limited regenerative efficacy. Biomaterials-based anti-senescence strategies offer a promising alternative. This study is the first to demonstrate that silicate bioceramics possess not only osteogenic properties but also intrinsic anti-senescence capabilities, laying the foundation for the concept of "Silicate Anti-Senescence (SAS)". Using hardystonite (Ca₂ZnSi₂O₇, ZnCS), one of the classic silicate-bioceramics, we reveal its biphasic biological function-delaying cellular senescence and promoting bone formation-through various formulations, including porous scaffolds, ionic extracts, and particle suspensions. In vitro, ZnCS effectively delays senescence of bone marrow mesenchymal stem cells (BMSCs) and enhances osteogenic differentiation. In vivo, ZnCS 3D scaffolds remodel the senescent microenvironment and accelerate osteoporotic bone regeneration, while oral administration of ZnCS particles exhibits significant anti-osteoporotic effects. Mechanistically, Zn²⁺ and SiO₃^2- ions released from ZnCS exert synergistic effects that converge on the PI3K-AKT-SIRT1 signaling axis, thereby attenuating senescence-associated programs and reinforcing osteogenic gene networks. Notably, compared to classic anti-senescence drugs (dasatinib and quercetin), ZnCS shows superior performance compared to the control groups in both anti-senescence and osteogenesis. The study provides new insights into developing anti-senescence strategies for age-related skeletal diseases with silicate-based bioceramics.