Immune regulation and repair of osteochondral defects using manganese-luteolin hydrogel scaffold.

To investigate the effects of a 3D-printed Mn-Lut nanoflower-loaded biphasic hydrogel scaffold on the immune response and regenerative potential in a rat osteochondral defect model. The Mn-Lut-loaded biphasic hydrogel scaffold was synthesized and evaluated for its mechanical properties and biocompatibility. In vitro experiments with rat bone marrow mesenchymal stem cells (BMSCs) and bone marrow-derived macrophages (BMDMs) were performed to evaluate cell differentiation, survival, and immune modulation. The scaffold's in vivo regenerative effects were tested in a rat osteochondral defect model. The Mn-Lut-loaded scaffold supported osteogenesis and chondrogenesis by promoting BMSC differentiation. It also facilitated macrophage polarization to the anti-inflammatory M2 phenotype, mitigating oxidative stress. Histological and Micro-computed tomography (CT) analysis of in vivo samples revealed significantly enhanced osteochondral regeneration, including improved trabecular bone formation, cartilage repair, and overall bone density. The manganese-luteolin (Mn-Lut) nanoflower-loaded biphasic hydrogel scaffold modulates the immune microenvironment and enhances osteochondral regeneration, offering a promising therapeutic approach for joint repair.