Polysaccharide-based self-assembled nanocomposites with synergistic anti-bacterial, anti-oxidant, and...

Infected wounds remain a critical clinical challenge, predominantly driven by Staphylococcus aureus (S. aureus, especially methicillin-resistant S. aureus, MRSA) biofilm formation, which triggers a vicious cycle of persistent infection, sustained inflammation, and progressive oxidative stress. Current clinical interventions fail to achieve simultaneous bacterial eradication, modulation of inflammation, and tissue regeneration, often with biocompatibility risks, whereas natural polysaccharide-based biomaterials offer a promising engineering strategy to address this dilemma. Herein, based on the nano-cocktail synthesis concept, we developed a caffeic acid (CA)-loaded nanocomposite (CA@ZSH) via green self-assembly from natural carbohydrate polymers (sodium alginate, SA; hyaluronic acid, HA) and zein for comprehensive infected wound therapy. CA was encapsulated in a homogeneous inner matrix of zein and bioactive polysaccharide HA, enabling stable drug loading/sustained release, along with HA-mediated regulation of inflammation and pro-regeneration. This core nanocomplex was further coated with polysaccharide SA as a hydrophilic shell to enhance colloidal stability and maintain a moist wound-healing microenvironment. CA@ZSH exhibited potent anti-S. aureus/MRSA activity via biofilm disruption, plus excellent free radical-scavenging, anti-inflammatory properties, and biocompatibility. In vivo, it markedly accelerated wound healing by upregulating CD31 and VEGF, thereby promoting wound closure, collagen deposition, and angiogenesis. This study provides a facile and robust polysaccharide-based nanotherapeutic engineering strategy for the management of wounds infected with drug-resistant bacteria.