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A Low-Cost Rodent Model of Diabetic Epibolous Wounds Mimics Human Chronic Wound Progression and Dystrophic Scar Formation
Phoebe Lee, BS, Shawn Jeffrey Loder, MD, Wayne Vincent Nerone, BS, Fuat Baris Bengur, MD, David Guerrero, BS, Rachel Ricketts, Lauren Kokai, PhD.
University of Pittsburgh Department of Plastic Surgery
2022-01-15
Presenter: Phoebe Lee
Affidavit:
Certified
Director Name: Kacey Marra
Author Category: Medical Student
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Background/Purpose: Chronic diabetic wounds and their resultant dystrophic scars are challenging to model in the preclinical space because of differences in rodent healing from human and consequently are effective, novel therapeutics are limited. We have previously demonstrated that tissue-edge inward folding mimicking the architecture of epibole mitigates contracture and restricts epithelialization. Here we demonstrate that murine epibolous wounds generate a humanized environment of sustained inflammatory infiltration, proliferative granulation, and ultimately resolve into reliably dystrophic scars.
Methods: Diabetic (db/db) mice chronic wounds were generated by incising skin flaps, which were sutured to the dermis side to create a folded skin edge. One cohort was maintained for 14-days and periwound tissues were harvested for flow cytometry: CD11b, Ly6G, and F4/80. Additional histologic samples were assessed for H&E, Trichrome, and for pan-keratin (epithelium) and alpha-smooth-muscle actin (myofibroblasts). A second cohort was maintained until closure up to 12-weeks for photographs and histology.
Results: Wounds remain open >40 days in obese diabetic animals (p<0.05). Epibolous wounds demonstrated reduced frequency of epithelialization as defined by pan-keratin signaling. Epibolous wound demonstrate neutrophil-dominant inflammatory infiltrate up to 2-weeks with simultaneous enrichment of macrophage/monocyte populations (p<0.05). When allowed to proceed to maturation, scars from epibole injuries remained significantly larger (p<0.05). All epibolous injuries show histologic evidence of dystrophic healing.
Discussion/Conclusion: Wound-edge inversion prolongs inflammation, transitions to a more human-relevant granulation pattern, and a consistent dystrophic scar without need for thermal, radiological, chemical or biological interference - enhancing our preclinical ability to study and intervene in chronic wounds.
