Engineering a therapeutic deferoxamine-mesoporous silica-naringin/poly(L-lactic acid) scaffold to reverse ferroptosis-mediated imbalance and promote osteogenic differentiation in osteoporotic microenvironment

Osteoporosis is characterized by disrupted bone metabolism, iron overload, and chronic inflammation, which collectively impair bone regeneration. Ferroptosis, an iron-dependent form of cell death, exacerbates bone loss by inducing oxidative stress and disrupting the immune microenvironment. To address these challenges, we developed a DFO-MS-NG/PLLA scaffold using selective laser sintering. This scaffold integrates deferoxamine (DFO) for iron chelation and naringin (NG) for immunomodulation within a mesoporous silica (MS) matrix. In vitro experiments demonstrated that the scaffold effectively inhibits ferroptosis by reducing intracellular iron and reactive oxygen species (ROS) levels, promotes osteogenic differentiation of mesenchymal stem cells (mBMSCs), and modulates macrophage polarization towards the anti-inflammatory M2 phenotype. A co-culture system with mBMSCs and macrophages under iron-overloaded conditions further confirmed the scaffold's ability to enhance bone formation by mitigating ferroptosis and reprogramming the immune microenvironment. This innovative scaffold design offers a promising strategy for osteoporotic bone defects treatment by simultaneously addressing iron overload, inflammation, and impaired osteogenesis.