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LPS\u2010scavenging strategies are often limited by the poor accessibility of lipid A, the bioactive core of LPS, which is shielded by variable oligosaccharide structures and embedded in bacterial membranes. To address this, a synergistic LPS\u2010binding hydrogel (OCMC\u2010PMBP) is developed, combining polymyxin B (PMB) for lipid A\u2010targeted bacterial lysis and polyethyleneimine (PEI) for electrostatic LPS capture. This system is applied to oronasal\u2010perforating wounds, a complex and infection\u2010prone condition associated with cleft palate repair. Clinical microbiome analysis and murine models reveal that LPS\u2010TLR4 signaling contributes to immune dysregulation and impaired healing. OCMC\u2010PMBP treatment reduces LPS levels, restores microbiota balance, suppresses inflammation, and accelerates epithelial regeneration and collagen remodeling. 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