ABSTRACT Early burst ion release of biodegradable alloys, such as Zn 2 + , often triggers inflammation and impairs bone formation, which affects the clinical application of biodegradable alloys. Here, a multifunctional hydrophilic selenium‐containing polyurea (SePUA) is designed with a tunable ratio of selenium‐containing groups to hydrophilic groups. The SePUA can form stable Se‐metal coordination, achieving controlled ion release of biodegradable alloys, and simultaneously leverages the biological functions of selenium to realize immuno‐osteogenic synergistic modulation. Single‐cell RNA sequencing reveals that SePUA accelerates the shift from acute inflammation to a healing‐permissive immune environment. It reduces early Zn 2 + release and achieves controllable selenium release, thereby suppressing neutrophil chemotaxis and maturation, recruiting macrophages, activating the KEAP1‐NRF2‐SEPP1 pathway to decrease intracellular reactive oxygen species (ROS) and drive M2 polarization. Simultaneously, SePUA upregulates the stemness‐associated NR2F2‐SOX2/NANOG axis in MSCs and enhances their osteogenic differentiation capacity, thereby promoting new bone formation around the implants. This work develops a facile, multifunctional bioactive hydrophilic SePUA for the coating of biodegradable alloys that integrates ion release control, immunomodulation, and osteogenesis, offering critical support for the clinical translation of biodegradable alloys.
Fu et al. (Thu,) studied this question.