The Nuclear Damage-Response Code of Cutaneous Wound Repair: Mechanotransduction, cGAS-STING, Senescence, and Regenerative Interfaces
- 1Department of Chemistry, Yeungnam University, Gyeongsan 38541, Republic of Korea
- 2Department of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Republic of Korea
- 3Faculty of Medicine, Ala-Too International University, Bishkek 720048, Kyrgyzstan
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.
Related
- Laser-programmed anisotropic hierarchical host bone interfaces for mechanotransduction-guided osseointegration
- Regenerative therapies in rehabilitation with interfaces with occupational medicine, geriatrics, and oncology: the example of extracorporeal shock wave therapy
- Muscle macrophage regenerative response after squalene-adjuvanted influenza vaccination is associated with type II-skewed response and is reduced with age
- Comparative Evaluation of Large Language Model Interfaces in Third Molar Surgery Complication Scenarios: Response Quality, Clinical Content, Potential Clinical Risk, Readability, and Externally Observable Response Latency—A Cross-Sectional Comparative Benchmark Study
- The mitochondrial unfolded protein response in human microglia disrupts neuronal–glial communication and promotes senescence
BibTeX
@article{akhtar2026nuclear,
title = {{The Nuclear Damage-Response Code of Cutaneous Wound Repair: Mechanotransduction, cGAS-STING, Senescence, and Regenerative Interfaces}},
author = {Muhammad Saeed Akhtar and Mohammad Aslam and Mirza Masroor Ali Beg},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16101427},
url = {https://www.mdpi.com/2218-273X/16/10/1427},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The Nuclear Damage-Response Code of Cutaneous Wound Repair: Mechanotransduction, cGAS-STING, Senescence, and Regenerative Interfaces
AU - Muhammad Saeed Akhtar
AU - Mohammad Aslam
AU - Mirza Masroor Ali Beg
PY - 2026
DA - 2026/10/01
JO - Biomolecules
DO - 10.3390/biom16101427
UR - https://www.mdpi.com/2218-273X/16/10/1427
AB - 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.
SN - 2218-273X
ER -