Injectable hydrogels for Fenton-like Mn2+/Fe2+ delivery with enhanced chemodynamic therapy prevent osteosarcoma recurrence and promote wound healing after excision surgery

Local recurrence of osteosarcoma and wound healing after excision surgery are major challenges in clinical research. The present anti-tumor treatments could inhibit normal tissues, resulting in difficulties in surgical wound healing. In this study, we constructed an injectable hydrogel as a platform to co-deliver MnO₂ nanoparticles and ferrocene Fc, termed as (MnO₂/Fc)@PLGA for osteosarcoma treatment and wound healing after excision. By simple local injection, the hydrogel could form a protective barrier on the surgical wound after osteosarcoma excision, which could promote wound healing and steady release of MnO₂/Fc nanoparticles. The released MnO₂/Fc might undergo the Fenton reaction through Mn²⁺/Fe²⁺ to inhibit osteosarcoma cells with chemodynamic therapy (CDT). Furthermore, MnO₂ could catalyze endogenous H₂O₂ to produce O₂, which eliminates the adverse effects of H₂O₂ and remodels the hypoxic state in the local lesions. The increased O₂ facilitated surgical wound healing and anti-tumor effects by regulating the hypoxia inducible factor-1 functions. In conclusion, (MnO₂/Fc)@PLGA hydrogel could effectively prevent local recurrence of osteosarcoma and promote wound healing after excision surgery, thereby providing a novel strategy for tumor treatment and tissue repair.