Polysaccharide-based aerogel dressing integrated with MOF-loaded quercetin with multifunctional effects for promoting infected wound healing

Infectious wounds disrupt the progression through the stages of wound healing, resulting in the development of chronic wounds. However, the current therapeutic approach is limited and requires repeated administrations. A major challenge in infectious wounds is to achieve sustained drug release. Herein, quercetin with anti-inflammatory and antibacterial properties was encapsulated within amino-functionalized UIO-66 metal-organic framework (MOF) to form MOF@Que NPs. MOF@Que NPs were then loaded into an aerogel constructed with agarose, aldehyde hyaluronic acid, and carboxymethyl chitosan to obtain ACA-MOF@Que for targeting different phases of wound healing. The polysaccharide-based aerogel was formed by the entanglement of polymer chains and the Schiff base reaction, which exhibited uniform pore structures and low-swelling properties. Furthermore, the ACA-MOF@Que aerogel also exhibited antioxidant, anti-inflammatory, and antibacterial properties. In vivo and in vitro experiments confirmed that the ACA-MOF@Que aerogel could promote hemostasis in the initial stage of wound healing, reduce cellular inflammatory infiltration, and inhibit the inflammatory response by regulating macrophage polarization during the inflammatory stage of wound healing. Finally, the ACA-MOF@Que aerogel could promote angiogenesis and increase collagen deposition in the later stage of wound healing. Compared with the untreated group, the wounds of rats treated with the ACA-MOF@Que aerogel had almost completely healed on the 14th day. Therefore, the ACA-MOF@Que aerogel plays multiple roles at various stages of wound healing, providing a promising therapeutic approach for the clinical application of chronic wounds.