A Hydrogel Dressing Integrated With Dissolving Microneedle Array Enables Spatiotemporal Cascade Reaction for Effective Diabetic Chronic Wound Treatment

The spatial heterogeneity of pathological factors in diabetic chronic wounds (DCWs) limits the development of effective treatment strategies. Here, a hydrogel-based wound dressing integrated with a dissolving microneedle array (H@MN) that orchestrates a novel spatiotemporal cascade reaction strategy is presented. Compared to the classical temporal cascade reaction, the spatiotemporal cascade reaction is characterized by spatially compartmentalized catalysts, which rely on the cross-regional diffusion of initial reaction products to the subsequent catalyst site to drive the sequential catalytic processes. Targeting the pathological features of DCWs, the glucose oxidase (GOX)-, superoxide dismutase (SOD)-, and catalase (CAT)-catalytic reactions are selected, which are catalyzed by natural enzymes or nanozymes. By integrating these catalysts into a spatiotemporal cascade reaction within the H@MN, it can intervene in and dynamically modulate the pathological factors in different spatial domains of DCWs at various temporal stages. Both in vitro and in vivo experiments confirm that the H@MN-enabled spatiotemporal cascade reaction, when combined with photothermal therapy, achieves superior healing efficacy in DCWs. The H@MN-enabled spatiotemporal cascade reaction is believed to inspire a generalizable strategy for treating diverse diseases characterized by spatially varied pathological microenvironments, offering a promising paradigm for advanced therapeutics.