biostudies-literatureUnknown14(9)Zhou H<b>Background:</b> The repair of osteoporotic bone defects remains challenging due to excessive reactive oxygen species (ROS), persistent inflammation, and an imbalance between osteogenesis and osteoclastogenesis. <b>Methods:</b> Here, an injectable H₂-releasing hydrogel (magnesium@polyethylene glycol-poly(lactic-co-glycolic acid), Mg@PEG-PLGA) was developed to remodel the challenging bone environment and accelerate the repair of osteoporotic bone defects. <b>Results:</b> This Mg@PEG-PLGA gel shows excellent injectability, shape adaptability, and phase-transition ability, can fill irregular bone defect areas via minimally invasive injection, and can transform into a porous scaffold <i>in situ</i> to provide mechanical support. With the appropriate release of H₂ and magnesium ions, the 2Mg@PEG-PLGA gel (loaded with 2 mg of Mg) displayed significant immunomodulatory effects through reducing intracellular ROS, guiding macrophage polarization toward the M2 phenotype, and inhibiting the IκB/NF-κB signaling pathway. Moreover, <i>in vitro</i> experiments showed that the 2Mg@PEG-PLGA gel inhibited osteoclastogenesis while promoting osteogenesis. Most notably, in animal experiments, the 2Mg@PEG-PLGA gel significantly promoted the repair of osteoporotic bone defects <i>in vivo</i> by scavenging ROS and inhibiting inflammation and osteoclastogenesis. <b>Conclusions:</b> Overall, our study provides critical insight into the design and development of H₂-releasing magnesium-based hydrogels as potential implants for repairing osteoporotic bone defects.Theranostics3739-3759https://www.ebi.ac.uk/biostudies/studies/S-EPMC11209720biostudies-literatureAn injectable magnesium-loaded hydrogel releases hydrogen to promote osteoporotic bone repair via ROS scavenging and immunomodulation.PMC11209720He ZCao YDeng ZZhou HChu LYu KLiang BfalseAn injectable magnesium-loaded hydrogel releases hydrogen to promote osteoporotic bone repair via ROS scavenging and immunomodulation.<b>Background:</b> The repair of osteoporotic bone defects remains challenging due to excessive reactive oxygen species (ROS), persistent inflammation, and an imbalance between osteogenesis and osteoclastogenesis. <b>Methods:</b> Here, an injectable H₂-releasing hydrogel (magnesium@polyethylene glycol-poly(lactic-co-glycolic acid), Mg@PEG-PLGA) was developed to remodel the challenging bone environment and accelerate the repair of osteoporotic bone defects. <b>Results:</b> This Mg@PEG-PLGA gel shows excellent injectability, shape adaptability, and phase-transition ability, can fill irregular bone defect areas via minimally invasive injection, and can transform into a porous scaffold <i>in situ</i> to provide mechanical support. With the appropriate release of H₂ and magnesium ions, the 2Mg@PEG-PLGA gel (loaded with 2 mg of Mg) displayed significant immunomodulatory effects through reducing intracellular ROS, guiding macrophage polarization toward the M2 phenotype, and inhibiting the IκB/NF-κB signaling pathway. Moreover, <i>in vitro</i> experiments showed that the 2Mg@PEG-PLGA gel inhibited osteoclastogenesis while promoting osteogenesis. Most notably, in animal experiments, the 2Mg@PEG-PLGA gel significantly promoted the repair of osteoporotic bone defects <i>in vivo</i> by scavenging ROS and inhibiting inflammation and osteoclastogenesis. <b>Conclusions:</b> Overall, our study provides critical insight into the design and development of H₂-releasing magnesium-based hydrogels as potential implants for repairing osteoporotic bone defects.2024-01-01T00:00:00Z20242026-03-16T14:54:25.982Z2025-08-15T03:07:05.897ZS-EPMC112097203894805410.7150/thno.97412