An Injectable Hydrogel System with Mild Photothermal Effects Combined with Ion Release for Osteosarcoma‐Related Bone Defect Repair

Abstract Osteosarcoma, a common invasive malignant bone disease, presents therapeutic challenges due to the persistent problem of incomplete resection during surgical treatment. This often results in postoperative tumor recurrence and metastasis, and large‐scale bone defects are difficult to self‐repair, seriously affecting patient health. In this study, a dual‐ion doped organic‐inorganic composited SOH₁(CP)₁ injectable hydrogel system is successfully designed and constructed. This system consists of sericin protein grafted with hydrazide bonds, oxidized chondroitin sulfate, Se and Mg co‐doped HAp nanorods, and polydopamine‐coated CaO₂ nanospheres. The system displays strong anti‐tumor activity due to its mild photothermal effects combined with the chemotherapeutic efficacy of SeO₃²⁻. Because the degradation behavior of hydrogel matches the bone repair cycle, including the nutritional support of hydrogel skeleton degradation products to promote bone cell proliferation, and the positive regulation of Ca²⁺, Mg²⁺, and PO₄³⁻ released via the degradation of inorganic nanoparticles to promote bone differentiation, the system shows excellent bone defect repair efficacy. Importantly, this system achieves 100% tumor inhibition after 18 days, while ensuring complete bone repair after 12 weeks. Hence, the SOH₁(CP)₁ injectable hydrogel system, which displays both high anti‐osteosarcoma efficacy and strong bone repair properties, can serve as a new tool for osteosarcoma‐related bone defect repair.