Injectable hydrogels for Fenton-like Mn 2+ /Fe 2+ 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 MnO nanoparticles and ferrocene Fc, termed as (MnO /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 MnO /Fc nanoparticles. The released MnO /Fc might undergo the Fenton reaction through Mn /Fe to inhibit osteosarcoma cells with chemodynamic therapy (CDT). Furthermore, MnO could catalyze endogenous H O to produce O , which eliminates the adverse effects of H O and remodels the hypoxic state in the local lesions. The increased O facilitated surgical wound healing and anti-tumor effects by regulating the hypoxia inducible factor-1 functions. In conclusion, (MnO /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.