Bioinspired Integrated MgH₂ 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 (MgH₂-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 (Mg²⁺) and hydrogen gas (H₂). The released Mg²⁺ directly stimulates the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts, accelerating osteogenesis. Concurrently, Mg²⁺ and H₂ 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.