Mild Photothermal Stimulation Driven Nanoparticles Hybrid Dual‐Network Hydrogels for Bone Repair

ABSTRACT Bone defects arise from trauma, fractures, tumors, or infections, presenting significant treatment challenges. Effective repair requires concurrent angiogenesis and osteogenesis due to the importance of vasculature for nutrient supply. This study introduces a PDA@GelMA/HA‐DA/Fe 3+ hydrogel, where Fe 3+ ions crosslink dopamine‐modified hyaluronic acid (HA‐DA) with gelatin methacryloyl (GelMA) to form a dual‐network hydrogel, also incorporating photothermal polydopamine (PDA) nanoparticles. In vitro and in vivo studies reveal that Fe 3+ enhances angiogenesis, while the hydrogel's photothermal properties improve bone repair in massive defects. In cell experiments, bone marrow mesenchymal stem cells (BMSCs) exhibit the highest osteogenic differentiation in the hydrogel + photothermal group, followed by the hydrogel group alone. qPCR and Western blot analyses confirm elevated expression of osteogenic genes and proteins in BMSCs treated with the hydrogel + photothermal method. Micro‐computed tomography (Micro‐CT) analyses show the most significant bone formation in the hydrogel + photothermal group, while control samples show limited mineralization. Histological staining indicates substantial bone tissue formation in the treatment groups, with increased expression of osteogenesis‐related proteins (OCN, OPG, RUNX2, ALP) and angiogenesis markers (CD31, VEGFA). Our study demonstrates that the PDA@GelMA/HA‐DA/Fe 3+ hydrogel promotes bone defect repair, with Fe 3+ mediating angiogenic effects and photothermal stimulation augmenting its osteogenic potential.