Biopolymer-based bone scaffold for controlled Pt (IV) prodrug release and synergistic photothermal-chemotherapy and immunotherapy in osteosarcoma

Achieving bone defect repair while preventing tumor recurrence after osteosarcoma surgery has consistently posed a clinical challenge. Local treatment with 3D-printed scaffolds loaded with chemotherapeutic drugs can exert certain effects in tumor inhibition and bone regeneration. However, the non-specific activation of chemotherapeutic drugs leads to high local toxic side effects and the formation of an immunosuppressive tumor microenvironment, thereby limiting their clinical application and therapeutic efficacy. To address this, we designed a Pt (IV) prodrug with low toxicity and minimal side effects, which releases Pt (II) in response to glutathione. This prodrug was grafted onto polydopamine (PDA) through an amidation reaction, resulting in a composite nanomaterial (PDA@Pt) that possesses both photothermal synergistic chemotherapy and immuno-oncological properties. Subsequently, we innovatively employed selective laser sintering technology to incorporate PDA@Pt into a poly (L-lactic acid)/bioactive glass matrix, successfully constructing a composite scaffold with dual anti-tumor and bone repair capabilities. The study revealed that the composite scaffold significantly inhibited the growth of osteosarcoma cells and activated the cGAS-STING pathway by inducing DNA damage, ultimately converting the 'cold tumor' into a 'hot tumor.' Additionally, the composite scaffold could induce osteogenic differentiation of bone marrow mesenchymal stem cells and exhibited excellent bone repair capabilities in vivo.