Bioinspired Integrated MgH ₂ Hydrogel Synergistically Modulates the Osteo‐Immune Microenvironment for Enhanced Bone Repair

ABSTRACT

Magnesium‐based biomaterials show great potential in bone regeneration due to their inherent biocompatibility, osteogenic activity, and ability to modulate the immune microenvironment. However, their rapid degradation rate remains a critical barrier to clinical translation. To address these challenges, we developed a magnesium hydride‐gelatin methacryloyl (MgH ₂ ‐GelMA) composite with sustained release of hydrogen gas and magnesium ions, featuring a bone‐mimetic organic–inorganic hybrid network. First, magnesium hydride microcrystals were coated with an inorganic silica layer to mitigate degradation; subsequently, the coated particles were embedded within an organic GelMA hydrogel matrix. The composite achieves controlled co‐release of magnesium ions (Mg ²⁺ ) and hydrogen gas (H ₂ ). The released Mg ²⁺ directly stimulates the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts, accelerating osteogenesis. Concurrently, Mg ²⁺ and H ₂ synergistically induce polarization of bone marrow‐derived macrophages (BMDMs) toward an anti‐inflammatory phenotype. During the active inflammatory phase, this polarization modulates the immune microenvironment and establishes a pro‐regenerative local niche. This study not only elucidates a novel ion‐gas synergistic mechanism but also provides innovative insights and theoretical foundations for advancing artificial bone materials from passive biomimetic replacement to active regenerative modulation.