Sustained Release of Magnesium Ions Mediated by a Dynamic Mechanical Hydrogel to Enhance BMSC Proliferation and Differentiation

[Image: see text] Hydrogel scaffolds are promising and widely applicable platforms for various therapeutic agents to facilitate bone tissue regeneration due to their biocompatibility and low immunogenicity. Nevertheless, the improvement of local administration efficiency and on-demand release of drugs from a hydrogel system is still an obstacle. In this work, we reported that a novel injectable hydrogel system was fabricated based on coordination of multiarm thiolated polyethylene glycol (PEG-SH) and magnesium ions for bone marrow-derived mesenchymal stem cell (BMSC) proliferation and differentiation. The dynamic nature coordination bond of Mg–S and the dynamic disulfide bond of S–S provide hydrogels with good mechanical performance and typical rheological behavior and thus endow the hydrogels with a satisfactory swelling rate and degradation property. Mg(2+) was incorporated in the system not only to act as an effective cross-linker to enhance the hydrogel network structure but also to mediate the sustained release of Mg(2+). Due to the controlled release of Mg(2+), the PEG-SH/Mg(2+) hydrogel can effectively improve BMSC proliferation and osteoblastic activity via the PI3K/Akt/GSK3β/β-catenin signal pathway in vitro. These findings indicated that the novel hydrogel controlled release of a Mg(2+) ion is viewed as a promising and flexible platform for bone regeneration clinically.