Work

The Nuclear Damage-Response Code of Cutaneous Wound Repair: Mechanotransduction, cGAS-STING, Senescence, and Regenerative Interfaces

Year: 2026

Type: review

Abstract: Chronic cutaneous wounds are often described as disorders of inflammation, infection, perfusion, or extracellular matrix turnover, yet these categories do not fully explain why a wound that initially detects injury fails to re-enter a coordinated program of repair. This Perspective proposes a unifying model in which the nucleus acts as a damage integrator at the wound edge. Mechanical strain, osmotic swelling, oxidative stress, chromatin fragmentation, and mitochondrial injury converge on nuclear-envelope tension, nuclear rupture, cytoplasmic deoxyribonucleic acid sensing, and senescence-associated transcription. When the signal is brief and spatially restricted, it can support leukocyte recruitment, keratinocyte migration, matrix remodeling, and early host defense. When it is amplified by diabetes, aging, tissue stiffness, biofilm-compatible inflammation, or defective autophagic and efferocytic clearance, the same pathway becomes a self-reinforcing loop that sustains interferon signaling, inflammasome activity, endothelial dysfunction, fibroblast memory, and impaired epidermal differentiation. The review integrates evidence from single-cell wound atlases, mechanobiology, innate immune deoxyribonucleic acid sensing, mitochondrial stress, macrophage biology, senescence, microbiome studies, and smart biomaterials. It argues that future wound therapeutics should not simply accelerate closure, but should classify and reset the temporal polarity of nuclear damage responses. Nucleus-aware dressings, local signal-gated inhibitors, senolytic or senomorphic interfaces, and biomaterials that reduce pathological mechanical memory may provide more precise ways to convert chronic wound fields into regenerative ones.

Source: Biomolecules

DOI: 10.3390/biom16101427

Authors: Muhammad Saeed Akhtar, Mohammad Aslam, Mirza Masroor Ali Beg

Institutions: Yeungnam University, Ala-Too International University

Language: English

Topic: Wound Healing and Treatments

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258