Hydroxyapatite injectable hydrogel with nanozyme activity for improved immunoregulation microenvironment and accelerated osteochondral defects repair via mild photothermal therapy

Osteochondral defect repair presents a significant clinical challenge due to the immune microenvironment at the injury site, which impairs osteogenesis. In this study, a Ce/MnHAp was developed by integrating it into an HES hydrogel. This bi-layered hydrogel system comprises an upper cartilage-mimicking layer composed of pure hydrogel and a lower subchondral bone-mimicking layer containing Ce/MnHAp. The HESH hydrogel exhibits dual responsiveness to pH and NIR laser irradiation, enabling spatiotemporally controlled release of the Ce/MnHAp and bioactive ions in response to physiological stimuli during the repair process. Upon release, Ce/MnHAp modulates the local immune micro-environment by ROS, inducing M2 macrophage polarization, restoring immune homeostasis, and improving osteogenic activity. Treatment with the NIR-irradiated HESH hydrogel significantly accelerated osteochondral regeneration over 12 weeks in a rabbit osteochondral defect model. These results highlight this multifunctional hydrogel system's therapeutic potential as an effective osteochondral tissue repair strategy.