A programmed oxidized alginate/chitosan sandwich-layered dressing for sequential regulation of diabetic wound healing

Chronic diabetic wounds remain a major clinical challenge due to persistent inflammation, excessive reactive oxygen species (ROS), and impaired angiogenesis. However, many wound dressings do not coordinate therapeutic delivery with the changing oxidative and angiogenic requirements of diabetic wound healing. Herein, we developed a sandwich-structured composite dressing (^DFOPLGA@^CGel) that enables spatiotemporally coordinated drug delivery to match the stage-specific demands of wound healing. The outer hydrogel layer, formed via dynamic Schiff-base crosslinking between oxidized sodium alginate (OSA) and chitosan, provides favorable injectability, tissue adhesion, and microenvironment responsiveness. Incorporation of curcumin nanocrystals into the OSA/chitosan hydrogel further improves drug dispersion and bioavailability, enabling rapid ROS scavenging and attenuation of early-stage inflammation. Meanwhile, the inner electrospun PLGA nanofiber membrane provides sustained deferoxamine (DFO) release, which was associated with increased HIF-1α expression and enhanced angiogenesis during the proliferative phase. This temporally programmed strategy synchronizes anti-inflammatory and pro-angiogenic processes, facilitating the transition from inflammation to tissue regeneration. In diabetic wound models, ^DFOPLGA@^CGel reduced intracellular oxidative stress, increased angiogenesis-related signals and vessel density, and accelerated wound-area reduction. Overall, this work highlights the importance of temporal regulation in biomaterial design and presents a promising platform for precise microenvironment modulation and chronic wound therapy.