Zinc silicate microspheres-mediated bacterial metabolic interference and microenvironment remodeling for chronic wound repair

Chronic wounds have presented a significant clinical challenge due to persistent infection, uncontrolled inflammation, and impaired tissue regeneration. Existing therapeutic platforms have failed to integrate these critical aspects into a single, cohesive strategy. To address this, a novel multifaceted agent, zinc silicate flower-like microsphere (ZnSi FMPs), was designed with controlled hierarchical architecture to achieve chronic wound repair by mediating bacterial metabolic interference and microenvironment remodeling. The unique nanosheet structure with sustained Zn 2+ release endows ZnSi FMPs with favorable pH-independent antibacterial activity. This activity is mechanistically rooted in metabolic interference against Staphylococcus aureus ( S . aureus ), including disruption of ABC transporters and inhibition of the biosynthesis of essential amino acids ( valine, leucine, isoleucine ) and ribosomes . Concurrently, ZnSi FMPs can promote microenvironment remodeling by modulating inflammatory responses and angiogenesis, evidenced by suppressed inflammation mediated by the complement and coagulation cascades pathway and robust activation of the Areg/HB-EGF -mediated ErbB signaling pathway . Hence, in both S. aureus -infected and diabetic wound models (mice and minipigs), ZnSi FMPs exhibited superior chronic wound healing capacity compared with commercial silver sulfadiazine® (AgSD) and 45S5 bioglass®. This improved healing was achieved through enhanced antibacterial activity, anti-inflammatory effects, and angiogenesis, accompanied by elevated expression of CD163, CD206, CD31 and α-SMA . By synergizing bacterial metabolic interference with microenvironment regulation, ZnSi FMPs effectively facilitate tissue healing and provide a promising candidate for clinical wound treatment.