Unidirectional moisture-transporting, thermoregulating, and antimicrobial aerogel dressing orchestrates a pro-regenerative microenvironment for pressure ulcer treatment.

Abstract

Persistent pressure-shear coupled injury traps pressure ulcer wounds in a sustained ischemia-reperfusion cycle, leading to mitochondrial membrane potential collapse and mtDNA leakage in macrophages. This mitochondrial dysfunction amplifies intracellular ROS accumulation, disrupts inflammatory resolution, and blocks the transition from inflammation to proliferation, ultimately resulting in non-healing or delayed healing pressure ulcers. Here, we report a Janus hierarchical porous aerogel (OBP2GM) fabricated via directional ice-templating combined with electrospinning, designed to integrate multi-dimensional wound microenvironment regulation within a single construct. The electrospun top layer incorporates phase-change microspheres to provide mild, adaptive thermal buffering around physiological skin temperature (32-35 °C), while its highly porous fibrous architecture enables efficient bacterial interception. The underlying aerogel layer features vertically aligned microchannels that support rapid unidirectional fluid transport, ensuring effective exudate drainage and moisture balance. More importantly, the polysaccharide-polyphenol network within the aerogel actively regulates macrophage mitochondrial homeostasis by activating the PINK1/Parkin-mediated mitophagy pathway, facilitating the clearance of severely damaged mitochondria while preserving functional ones. This process restores mitochondrial membrane potential (ΔΨm↑, relative fluorescence intensity 69.22%), suppresses excessive ROS generation, promotes macrophage polarization toward the pro-regenerative M2 phenotype, and enhances HUVEC tubulogenesis by nearly threefold. In a murine pressure ulcer model, OBP2GM markedly accelerated wound re-epithelialization, demonstrating a materials-based strategy for mechanical-mitochondrial-immune synergistic repair of pressure ulcers.