Novel Surgical Epibole Model for Humanization of Chronic Wound Healing in Mice
Phoebe L Lee1,2, Shawn Loder2, Lauren Kokai2 and Peter J. Rubin2
1University of Pittsburgh School of Medicine, Pittsburgh, PA, 2Department of Plastic Surgery, UPMC, Pittsburgh, PA
Background: Representative small animal models approximating human healing are critical to advance wound research. Current murine chronic wounds models inadequately represent clinically recalcitrant wounds as anatomical differences in murine skin support closure via robust contraction and rapid reepithelization without significant granulation. Furthermore, models employing deleterious mutations or chemicals have limited clinical relevance. To overcome these limitations, we propose a novel chronic wound mouse model utilizing the architecture of epibole to mitigate contracture and epithelialization, pre-disposing mice to chronic wound development.
Methods: Male C57BL/6J control (wt/wt) and diabetic (db/db) mice received bilateral 6mm excisional wounds. Each wound was stratified as either untreated control or chronic model. Chronic wounds were generated by i) silicone stenting; ii) single topical dose of 3-amino-1,2,4-triazole and mercaptosuccinic acid; or iii) our novel epibole model. Epibole was generated by incising skin flaps, which were sutured to the dermis side to create a folded skin edge.
Results: Two weeks after wounding, epibolous wounds retained a significantly larger percent of the original wound area compared to untreated wounds in both wt/wt (37.8% vs. 10.6%, p=0.025) and db/db (115% vs. 7.2%, p<0.0001) mice. In wt/wt mice, the epibole model remained larger vs. either the stented (15.1%, p=0.16) or chemical wounds (0.93%, p=0.0020). This was similarly consistent for db/db epibole vs. stented (28.4%, p=0.0027) or chemical (63.9%, p=0.057) wounds.
Conclusion: Epibolous wound-edge folding represents a simple, chemical-free, stent-free surgical intervention to delay wound closure in mice. Consequently, this technique is a promising advancement in modeling chronic wound architecture in small animals.
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