Ligand-metal charge transfer-enabled copper-gallate nanozyme rescue oxidative stressed reparative cells for inflammatory dental tissue regeneration.

Dental tissue regeneration is often challenged by the hostile inflammatory microenvironment and the dysfunction of reparative cells due to oxidative stress. This study presents a reactive oxygen species (ROS)-scavenging nanozyme induced by ligand-to-metal charge transfer, engineered as a multifunctional capping material through the in situ growth of copper-gallate (CuGA) on hydroxyapatite nanofibers (HAFs). The obtained CuGA@HAF demonstrates superior ROS-scavenging capacity through its multi-enzyme mimetic activity, effectively rescuing the function of dental pulp stem cells (DPSCs) under oxidative stress by restoring mitochondrial homeostasis. Simultaneously, it achieves immunomodulation by driving macrophage polarization toward a pro-regenerative phenotype under the lipopolysaccharide (LPS)-induced inflammatory condition. In vivo experiments further demonstrate the anti-inflammatory, dentin-regenerative, and pro-angiogenic properties of CuGA@HAF. This work introduces a facile nanozyme construction strategy that leverages simple modifications of calcium phosphate-based biomaterials, providing a versatile platform for inflammatory tissue regeneration.