<i>Turritopsis nutricula</i> ‐Inspired Engineered Biomimetic Skin Promoting Aged Wound Repair via DAZAP1 Phase Separation‐Related Mitochondrial Metabolism Reprogramming

Abstract

ABSTRACT Aging‐associated wound healing deficiency causes a variety of health complications and makes both economic and psychological burdens on patients greatly, with current therapies failing to address underlying pathophysiology and aging‐related impairments. Inspired by Turritopsis nutricula , we directly fabricated biomimetic skin matrix (BSM) from human adipose tissue (AT) by decellularization, then incorporated with amino‐functionalized apoptotic bodies (FABs) to construct a biomimetic skin (BSM@FABs). BSM@FABs effectively displayed high fibroblast affinity while reversing cellular senescence, accelerating migration, and stimulating neovascularization in aged wounds. Mechanistically, we identified a pioneering DAZAP1 liquid‐liquid phase separation (LLPS) triggered by BSM@FABs. These biomolecular condensates in the LLPS process enhanced tricarboxylic acid (TCA) cycle flux and oxidative phosphorylation (OXPHOS), concomitant with suppressed glycolysis and reduced mitochondrial reactive oxygen species, thereby resolving aging‐impaired mitochondrial dysfunction. Our work introduces a novel LLPS‐targeted strategy for aged wound treatment by reprogramming mitochondrial energy metabolism.