The magnesium-gelatin composite microsphere scaffold combining hydrogen gas release, magnesium ions, and dimethyl fumarate effectively suppresses pyroptosis-driven inflammation and restores bone homeostasis in female mice with osteoporosis. This novel therapeutic approach demonstrates that combining hydrogen therapy with pyroptosis blockade represents a promising strategy for treating osteoporosis and bone defects by remodeling the inflammatory microenvironment and promoting bone tissue repair.
Plain-Language Summary
Researchers developed a special scaffold (a porous support structure) made of gelatin, magnesium, and other compounds that slowly releases hydrogen gas into bone defects in female mice with osteoporosis. The scaffold works by reducing a type of inflammatory cell death called pyroptosis and using hydrogen's antioxidant properties to calm inflammation, while magnesium helps repair bone tissue. In tests on mice, this combination approach successfully reduced inflammation and improved bone healing.
Abstract
The treatment of osteoporosis and related bone defects remains challenging. This study identifies pyroptosis-driven inflammation as a key disruptor of bone homeostasis. To address this, we develop a magnesium-gelatin composite microsphere scaffold (GelMa/Mg/DMF MS) that exploit pyroptosis blockade and hydrogen-mediated inflammation regulation for osteoporosis treatment. This porous microsphere scaffold is implanted into bone defects to achieve the sustained release of hydrogen gas, magnesium ions (Mg2+), and dimethyl fumarate (DMF). DMF act by activating the nuclear factor erythroid-related factor 2 to prevent osteoblast pyroptosis, and combine with the antioxidant effects of hydrogen, effectively remodel the inflammatory microenvironment and create favorable conditions for the restoration of bone homeostasis. Mg2+ further expedite bone tissue repair. These results demonstrate that the GelMa/Mg/DMF MS effectively reverse inflammatory microenvironments both in vivo and in vitro, resulting in significant tissue repair. These results suggest the combination of hydrogen therapy and pyroptosis blockade as a potential therapeutic strategy.
