A biocompatible visible-light-crosslinkable dimethylglycine grafted gelatin hydrogel promotes BMSCs osteogenesis by suppressing ROS-induced M1 macrophage polarization.

Photocrosslinkable hydrogels are widely used as scaffolds for bone repair and regeneration. However, insufficient biological safety and limited osteogenic ability have limited their clinical application prospects. Herein, a visible-light-crosslinkable GMD hydrogel was developed by grafting natural N, N-dimethylglycine (DMG) onto methacrylated gelatin (GelMA) to enhance the osteogenic potential of bone marrow mesenchymal stem cells (BMSCs). The hydrogel achieves rapid gelation within ∼15 s under visible light irradiation using FMN as the photoinitiator and DMG itself as the co-initiator, while exhibiting excellent injectability and 3D printability. The introduced hydrophobic dimethylamino groups induce hydrophobic interactions between GelMA molecular chains, significantly improving the mechanical and adhesive strength of the hydrogel. Biological experiments demonstrated that the GMD hydrogel effectively scavenges reactive oxygen species (ROS) and promotes glutathione recycling via the SIRT1/PGC-1α/Nrf2 signaling axis, thereby suppressing ROS-induced activation of the p-Syk/NF-κB pathway. Consequently, M1 macrophage polarization is inhibited, creating a favorable osteoimmune microenvironment that enhances osteogenic differentiation of BMSCs. This was evidenced by upregulation of osteogenic markers (ALP, BMP, RUNX2, ColI, OCN) and increased mineralization. The GMD hydrogel represents a promising biomaterial platform for bone repair and regeneration.