Pomegranate-inspired bionic microgel/periosteum composite harnessing reactive oxygen species for immune-engineered...

Excessive reactive oxygen species (ROS) and unresolved inflammation create a hostile microenvironment that compromises regeneration in critical-sized bone defects. Here, we developed a pomegranate-inspired bionic microgel/periosteum composite (PBC) featuring a hierarchical "membrane-seed" modular design, in which a periosteum-mimetic PDA/PLLA membrane provided not only ROS counteraction but also a continuous protective interface and defect compartmentalization. Conductive GelMA/PEDOT:PSS microgels serving as the "seeds" enabled enhanced and prolonged ROS clearance as well as conformal filling of irregular geometries, and increased cell-material contact. The PBC system was shown to possess adequate mechanical, electro-chemical and anti-ROS properties as well as high biocompatibility. In an inflammatory environment, the PBC enabled macrophage polarization toward reparative phenotype, remarkable ROS clearance and osteogenic differentiation, which were further enhanced under electrical stimulation. Transcriptomic analyses together with Seahorse measurements indicated that PBC remodelled energy metabolism of macrophages, and intercellular mitochondrial transfer was observed as a potential contributory route in macrophage-osteoblast coupling-based bone regeneration. In a rat critical-sized mandibular defect model, PBC implantation improved bone formation and defect bridging and was accompanied by moderated early inflammatory signals. Collectively, the PBC system provided a modular periosteal substitute integrating structural biomimicry with sustained redox buffering and immune-informed regeneration.