Research Paper Volume 15, Issue 8 pp 2852—2862

A chronic wound model to investigate skin cellular senescence

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Figure 1. Oxidative stress-induced wounding results in a chronic wound with increased SA-β-gal expression and SASP burden. (A) Study design: an acute wound model (top) created with skin punch biopsy and vehicle (normal saline) application and a chronic wound model (bottom) created with localized oxidative stress induced by intraperitoneal 3-amino-1,2,4-trizole (ATZ; 1 g/kg) prior to wounding and topical mercaptosuccinic acid (MSA; 150 mg/kg) after wounding in wild-type C57BL/6 J mice (20-weeks-old). (B) Representative images of wound healing and histological images from hematoxylin and eosin-stained sections of acute versus chronic wounds (n = 6 in each group at day 14), low power magnification. (C) Wound contracture assessment as a function of % wound closure. (D) Wound contracture assessment as a function of area (mm2). (E) SA-β-gal staining indicates presence of senescent cells (red arrows) in the epidermis and dermis 14-days post-wounding. (F) Relative expression of senescence and SASP markers in the skin after 14-days in normal skin, acute wounds, and chronic wounds. Measurements are expressed as mean ± SEM. Statistical analysis was performed using Student’s t-test; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.