Injectable Glycyrrhizic Acid Hydrogel Microspheres With Synergistic Anti‐Senescence and Osteogenic Effects for Osteoporosis Therapy

Osteoporosis is an age-related bone disease closely associated with the accumulation of senescent cells in the bone marrow microenvironment, a pathological feature that is not fully addressed by current biomaterial-based therapies. Targeting cellular senescence and its associated inflammatory microenvironment presents a promising strategy for mitigating osteoporosis progression. Glycyrrhizic acid (GA), a naturally occurring triterpenoid, has been shown to alleviate cellular senescence in various age-related disorders. Herein, injectable GA/gelatin methacrylate hydrogel microspheres (GA@GelMA) were developed using microfluidic technology to enable sustained GA release. The microspheres demonstrated multiple functionalities in vitro, including suppression of cellular senescence, induction of M1-to-M2 macrophage polarization, and enhancement of osteogenic differentiation in bone marrow stem cells (BMSCs). In an ovariectomized (OVX) mouse model of osteoporosis, local administration of GA@GelMA microspheres significantly promoted bone formation and alleviated the senescence-associated inflammatory microenvironment. These GA@GelMA microspheres provide a multifunctional strategy integrating osteogenesis promotion and senescence modulation for the treatment of osteoporosis.