Inorganic materials to prevent liquefactive necrosis and improve wound healing: A role of infection control across ischemic models.

Liquefactive necrosis, clinically manifesting as wet gangrene, is a catastrophic complication of ischemic wounds driven by bacterial overgrowth, proteolytic tissue lysis, and loss of structural integrity; current treatments remain largely limited to surgical debridement or amputation. Here, we show that inorganic biomaterial films releasing hydroxide ions, with or without oxygen and hydrogen peroxide, can markedly inhibit the development and spread of liquefactive necrosis in ischemic skin and cartilage. A calcium peroxide (CaO2) loaded film in alginate hydrogel was evaluated in ischemic rat dorsal wounds and in a more clinically analogous ischemic rabbit ear wound model. CaO2 films were benchmarked against a composition-matched, non-oxygenating calcium hydroxide (Ca(OH)2) formulation to decouple alkaline pH mediated antibacterial effects from combined delivery of pH, oxygen, and hydrogen peroxide. CaO2 films sustained localized hyperoxia for up to 3 days, yet both CaO2 and Ca(OH)2 restored ischemic rat wound closure to non-ischemic levels and significantly reduced bacterial burden. In rabbits, treated ischemic wounds reached 75-80% closure versus ∼50% in controls after 2.5 weeks. Untreated ischemic rabbit ears developed liquefactive necrosis breaching auricular cartilage and anterior skin in 83% of cases, whereas CaO2 and Ca(OH)2 films reduced cartilage necrosis by 56-79% and dermal necrosis by 78-93%. These data indicate that neither oxygen nor hydrogen peroxide delivery is strictly required to improve ischemic wound healing or prevent wet gangrene-like tissue failure, and highlight hydroxide-mediated antibacterial and microenvironmental modulation rather than bacterial elimination as a key mechanism by which these inorganic chemistries stabilize ischemic tissue.