Osteoradionecrosis of the jaw (ORNJ) can lead to debilitating complications, and current therapies carry risks of tissue damage and vascular dysfunction. Here, a jaw vascular unit (JVU) biomimetic nanozyme is developed by coating a Mn/Ca dual-atom site nanozyme (Mn-CaDSN) with a hybrid membrane (HM) derived from M2 macrophages and osteoinductive human bone marrow mesenchymal stem cells (HBMSCs).Mn-CaDSN exhibits synergistic superoxide dismutase-like, catalase-like, and glutathione peroxidase (GPx)-like activities, with the maximum GPx-like catalytic activity of Mn-CaDSN being 2.1 times higher than that of the Mn single-atom control. Density functional theory calculations indicate that the Ca site optimizes substrate adsorption and O–H bond cleavage by modulating the d-band center. HM coating can target JVU delivery, enhance cellular uptake, and reprogram irradiated macrophages to achieve M2 polarization and osteogenic differentiation.In irradiated cells, nanozymes simultaneously eliminate reactive oxygen/nitrogen species (RONS), activate mitochondrial autophagy, and inhibit cuproptosis. The loaded Dl-3-n-butylphthalide (NBP) further enhances angiogenesis in vivo. In a rat ORNJ model, NBP@Mn-CaDSN@HM promotes mucosal healing and increases bone volume fraction by rebalancing the immune-vascular-osteogenic microenvironment. This work establishes a JVU biomimetic paradigm combined with bimetallic nanozymes for comprehensive ORNJ therapy.

Original link

Advanced Materials ( IF 26.8 )

Pub Date : 2025-11-14

DOI: 10.1002/adma.202517968

Ziyu Chen,  Junlin Wang,  Yuhao Ruan,  Jikang Cao,  Huijun Jiang, Jiandong Jiang,  Fan Wu,  Shuilin Wu,  Yuli Wang