Mechanically adaptive injectable hydrogels with dual-role oxidized cyclodextrin for pH-responsive drug delivery in...

The management of chronically infected wounds remains challenging due to persistent bacterial colonization and unresolved inflammation. To address this, an injectable double-network hydrogel was developed to facilitate wound healing. Formation of the hydrogel occurred via a reversible Schiff base reaction between oxidized β-cyclodextrin (OCD) and α-lipoic acid-modified chitosan (LACS), imparting high injectability for thorough coverage of irregular wound sites. Notably, OCD played a dual role: encapsulating hydrophobic resveratrol via its hydrophobic inner cavity for pH-responsive release triggered by Schiff base bond cleavage, while also serving as a crosslinker by providing aldehyde groups for primary network formation. Upon UV exposure, a secondary disulfide bond network formed, enhancing mechanical stability and adaptability post-injection. The mechanical properties were tunable by adjusting OCD content to modulate Schiff base network density. In vitro, LCOD exhibited strong antibacterial, antioxidant, and biocompatible properties. In vivo results in a murine infected wound model showed that resveratrol-loaded LCOD promoted healing by reducing inflammation, enhancing collagen deposition, stimulating angiogenesis, and accelerating re-epithelialization. The multifunctional hydrogel combines ease of injection, tunable mechanical properties, and pH-triggered drug release, representing a promising therapeutic approach for managing chronic wounds.