Hypoxia-activated probiotic vesicle coating enables laminar-shear-protective angiogenesis and antibacterial effects...

In treating infectious bone defects, bacterial eradication alone is insufficient, as impaired blood perfusion characterized by low fluid shear stress (FSS) hampers angiogenesis, thereby compromising osteogenesis and delaying bone repair. Herein, we engineered a low-FSS-activated, pro-angiogenic implant coating with antibacterial properties. This coating comprises a Fe³⁺-tannic acid (Fe³⁺-TA) chelation network as the adhesive sublayer, anchoring black phosphorus (BP) nanosheets preloaded with metformin (Met), and is further capped by an outer layer of Lactobacillus animalis-derived extracellular vesicles (BEVs). The Fe³⁺-TA and BP components synergistically provide photothermal and photodynamic antibacterial activity, while the BEV layer promotes M2 macrophage polarization and modulates the sustained release of Met and phosphate ions from BP degradation, fostering a pro-regenerative microenvironment. Simultaneously, the BP-mediated photodynamic effect exacerbates local oxygen consumption, amplifying the angiogenic potential of Met under hypoxia. The hypoxia-activated Met lowers the FSS threshold required to enable a laminar shear-protective endothelial phenotype, even under pathological low-FSS conditions. This process drives orderly angiogenesis, restores microvascular perfusion, and supports downstream osteogenesis. Overall, this bioinspired coating integrates "hypoxia activation, vascular guidance, and laminar-flow protection" to promote angiogenesis and osteogenesis, and is augmented by synergistic antimicrobial and immunomodulatory benefits, offering a promising strategy for treating infectious bone defects.