Self-responsive H2-releasing microneedle patch temporally adapts to the sequential microenvironment requirements for optimal diabetic wound healing

Abstract

Oxidative stress regulation and synchronized promotion of angiogenesis are critical factors in the healing process of diabetic wounds. However, existing research often fails to fully consider the dynamic interplay between these two biological processes and their time-dependent roles in diabetic wound healing. This study innovatively introduces a novel hydrogen (H2)-releasing microneedle patch capable of precisely controlling the regulation of oxidative stress and the promotion of angiogenesis through a bidirectional responsive mechanism of microneedles and backing layers. Specifically, we employ ammonia borane (AB)-loaded mesoporous silica nanoparticles (MSN) as a source of H2, combined with polyvinyl pyrrolidone (PVP) to fabricate microneedles. This design effectively clears excessive reactive oxygen species (ROS) in deep tissues and promotes the M2 polarization of macrophages. Concurrently, we utilize cobalt-adsorbed graphene oxide (GO/Co2+) mixed with polyvinyl alcohol (PVA) to prepare backing layers, which not only release Co2+ upon the reduction of oxygen-containing functional groups in GO by H2 diffused from deep tissues to synergize with H2 for enhanced vascularization, but also endow the microneedle patch with near-infrared light-responsive antimicrobial properties, crucial for managing diabetic infected wounds. Through this innovative dual-action mechanism, our research significantly accelerates the healing process of infected wounds in a diabetic mouse model. Moreover, single-cell sequencing results further confirm the pivotal role of H2 in regulating oxidative stress, promoting macrophage M2 polarization, and stimulating angiogenesis. These results not only showcase the unique features of our microneedle patch but also offer new perspectives and therapeutic strategies for the treatment of diabetic wounds.