A bioadhesive antioxidant dual-crosslinked hydrogel mitigates endothelial pyroptosis to enhance ischemic flap survival.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Multiterritory perforator flaps are widely used in reconstructive surgery; however, distal regions, particularly the choke zone, remain highly susceptible to necrosis due to sustained ischemia, oxidative stress, and endothelial inflammatory injury that impair microcirculatory remodeling. Although stem cell-derived exosomes are promising cell-free therapeutics, their efficacy in ischemic flaps is often limited by poor local retention and rapid loss of bioactivity. Here, we develop a bioadhesive antioxidant hydrogel composed of oxidized hyaluronic acid-dopamine and sericin methacrylate (SerMA) to enable stable wet-tissue adhesion and sustained local delivery of hypoxia-preconditioned adipose-derived stem cell exosomes. This strategy attenuates oxidative stress, suppresses NLRP3 inflammasome activation and endothelial pyroptosis, and preserves mitochondrial and angiogenic function under ischemic conditions. In a rat multiterritory perforator flap model, local application of the exosome-loaded hydrogel significantly enhanced flap perfusion and survival, promoted vascular remodeling within the choke zone, and reduced inflammatory responses. Transcriptomic analysis further revealed suppression of inflammasome-associated pathways and enrichment of vascular remodeling programs. Collectively, this work presents a bioadhesive hydrogel-based exosome delivery strategy that stabilizes the i

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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