Abstract
Surface modification is crucial for improving bone-implant integration, but current coating technologies lack simplicity, efficiency, and multifunctionality needed for clinical use. Metal-phenolic networks (MPNs) are emerging as a promising biomaterial interface that addresses osseointegration challenges through precise physicochemical design. Our study introduces a gallic acid-arginine@zinc (GA-Arg@Zn) MPN coating that promotes favorable host responses in the following ways: (1) Immunomodulation: Shifting macrophages towards CD206+ anti-inflammatory phenotypes while reducing TNF-α, IL-1β, and IL-6 secretion to create an immunoregulatory environment that minimizes fibrous encapsulation. (2) Osteopromotion: Enhancing bone marrow stromal cell (BMSC) osteogenic differentiation by increasing ALP activity and OCN expression through modulation of the ionic microenvironment. (3) Biointerface Engineering: Establishing an immunologically favorable osteogenic microenvironment that boosts BMSC recruitment and mineralization capacity through paracrine signals from macrophages. This self-reinforcing “immuno-osseous” regenerative axis integrates material-induced immunomodulation with stem cell activation, representing a significant advancement in orthopedic interface engineering. The coating’s rapid aqueous deposition and inherent antibacterial properties further highlight its clinical promise. Graphical : Supplementary Information: The online version contains supplementary material available at 10.1186/s12951-025-03791-3.