Turritopsis nutricula-Inspired Engineered Biomimetic Skin Promoting Aged Wound Repair via DAZAP1 Phase...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Aging Research

Background:

• Aging significantly impairs wound healing, leading to complications and burdens.
• Current therapies inadequately address the pathophysiology of aging-related wound healing deficits.
• There is a need for innovative treatments that restore function in aged tissues.

Purpose of the Study:

• To develop a biomimetic skin substitute for treating aged wounds.
• To investigate the mechanism of action for promoting wound healing in aged skin.
• To explore a novel strategy targeting cellular senescence and mitochondrial dysfunction.

Main Methods:

• Fabrication of a biomimetic skin matrix (BSM) from human adipose tissue via decellularization.
• Incorporation of amino-functionalized apoptotic bodies (FABs) into BSM to create BSM@FABs.
• In vitro and in vivo assessment of BSM@FABs for fibroblast interaction, senescence reversal, migration, and neovascularization.
• Mechanistic investigation of DAZAP1 liquid-liquid phase separation (LLPS) and its effect on cellular metabolism.

Main Results:

• BSM@FABs demonstrated high fibroblast affinity and reversed cellular senescence in aged skin models.
• The biomimetic skin accelerated migration and stimulated neovascularization in aged wounds.
• DAZAP1 liquid-liquid phase separation (LLPS) was identified as a key mechanism triggered by BSM@FABs.
• LLPS enhanced mitochondrial oxidative phosphorylation (OXPHOS) and tricarboxylic acid (TCA) cycle flux while suppressing glycolysis and reducing reactive oxygen species (ROS), resolving mitochondrial dysfunction.

Conclusions:

• BSM@FABs represent a promising therapeutic for aged wound healing by addressing cellular senescence and mitochondrial dysfunction.
• The study introduces a novel strategy for aged wound treatment by targeting liquid-liquid phase separation (LLPS) to reprogram mitochondrial energy metabolism.
• This approach offers a new direction for regenerative medicine in treating age-related tissue repair deficits.