Comprehensive Osteosarcoma Treatment with Multifunctional Composite Hydrogels Enabling Combined Photothermal Cancer Ablation and Osteoinductive Tissue Regeneration

Abstract Osteosarcoma treatment can lead to considerable loss of bone tissue, creating a challenging microenvironment for recovery. Here, a novel biomaterial is described for tumor treatment via photothermal therapy and bone‐tissue regeneration. Multifunctional composite hydrogels can be fabricated by incorporating mineralized magnetic fibers (G‐mMFs) into a gelatin‐genipin hydrogel. The G‐mMFs exhibit notable temperature increases in response to near‐infrared irradiation, and superior disruption of tumor tissue follows hyperthermia therapy in a tumor‐bearing mouse model. G‐mMFs protect stem cells from the oxidative stress anticipated after tumor ablation, following significant increases in catalase and anti‐apoptotic gene expression. G‐mMFs demonstrate enhanced osteoinductivity, with nearly 90% of human adipose‐derived stem cells exhibiting osteogenic markers. Adenosine signaling–mediated osteogenesis and restoration of osteogenesis under oxidative stress can be demonstrated through stem‐cell differentiation in the presence of H 2 O 2 . In vivo, regeneration of bone tissue can be assessed using a calvarial bone‐defect mouse model, with nearly twice the amount of bone formation in the G‐mMF group compared with mice without implantation, along with a more mature bone‐tissue structure. Collectively, these study results present G‐mMFs as a multifunctional biomaterial that simultaneously addresses tumor ablation and bone regeneration, offering a promising strategy for the comprehensive treatment of osteosarcoma.