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Injectable Glycyrrhizic Acid Hydrogel Microspheres With Synergistic Anti-Senescence and Osteogenic Effects for
Yunchen Hong1,2,3, Xiangyu Liu2,3, Wenwen Mao2,3
1Department of Spinal Surgery, Jiangdu People's Hospital Affiliated With Yangzhou University, Yangzhou University, Yangzhou, P. R. China.
Abstract:
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.
Insights
New hydrogel microspheres deliver glycyrrhizic acid to combat osteoporosis by reducing cellular senescence and inflammation, promoting bone growth in preclinical models.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Gerontology
Background:
- Osteoporosis is linked to senescent cells in bone marrow, a problem current therapies don't fully address.
- Cellular senescence and its inflammatory effects are key targets for osteoporosis treatment.
- Glycyrrhizic acid (GA) shows potential in alleviating cellular senescence.
Purpose of the Study:
- To develop injectable GA/gelatin methacrylate hydrogel microspheres (GA@GelMA) for sustained GA release.
- To evaluate the efficacy of GA@GelMA in treating osteoporosis by targeting senescence and promoting bone formation.
Main Methods:
- Microfluidic technology was used to create injectable GA@GelMA microspheres.
- In vitro studies assessed senescence suppression, macrophage polarization (M1-to-M2), and bone marrow stem cell (BMSC) osteogenic differentiation.
- In vivo studies utilized an ovariectomized (OVX) mouse model of osteoporosis.
Main Results:
- GA@GelMA microspheres effectively suppressed cellular senescence in vitro.
- Microspheres induced M1-to-M2 macrophage polarization and enhanced BMSC osteogenic differentiation.
- Local administration of GA@GelMA in OVX mice promoted bone formation and reduced the senescence-associated inflammatory microenvironment.
Conclusions:
- GA@GelMA microspheres offer a multifunctional approach for osteoporosis treatment.
- This strategy integrates osteogenesis promotion with senescence modulation.
- The developed microspheres show promise for mitigating osteoporosis progression.
