Natural polysaccharide-engineered POP@ZIF-67 nanoparticles coordinate antibacterial activity, macrophage polarization, and osteogenesis for chronic osteomyelitis therapy.

Abstract

Chronic osteomyelitis is difficult to treat due to the interplay of bacterial colonization, excessive inflammation, and impaired bone regeneration. Here, we developed an engineered natural polysaccharide POP@ZIF-67 nanoplatform to modulate these interrelated pathological processes. ZIF-67 is an antimicrobial framework with porous properties, peroxidase-like catalytic activity, and acid-responsive release behavior; purslane polysaccharide (POP) was incorporated as an immunomodulatory component to mitigate the excessive inflammatory stimulation induced by ZIF-67. POP@ZIF-67 exhibits effective antibacterial and antibiofilm activity against Staphylococcus aureus; more importantly, the incorporation of POP transforms the biological action of ZIF-67 from primarily antibacterial stimulation into a multifunctional platform capable of suppressing excessive M1-like macrophage responses, promoting repair-related polarization, and improving the osteogenic microenvironment. In a mouse model of chronic osteomyelitis, POP@ZIF-67 reduced local bacterial load and inflammatory damage while promoting collagen deposition, bone remodeling, and osteogenic maturation, without significant systemic toxicity. Overall, the study introduces an "antimicrobial framework-immune buffering" strategy that reconciles the antimicrobial efficacy of metal-organic frameworks with their immunostimulatory limitations. By integrating various therapeutic approaches, POP@ZIF-67 provides a promising new synthetic paradigm for the treatment of chronic osteomyelitis and infectious bone defects.