Characterization of a preclinical model of chronic ischemic wound

Author:

Roy Sashwati1,Biswas Sabyasachi1,Khanna Savita1,Gordillo Gayle1,Bergdall Valerie2,Green Jeanne2,Marsh Clay B.3,Gould Lisa J.4,Sen Chandan K.1

Affiliation:

1. Comprehensive Wound Center, Davis Heart and Lung Research Institute, Departments of Surgery

2. Departments of Veterinary Preventive Medicine, The Ohio State University Medical Center, Columbus, Ohio

3. Departments of Internal Medicine, The Ohio State University Medical Center, Columbus, Ohio

4. Department of Surgery, University of Texas Medical Branch, Galveston, Texas

Abstract

Chronic ischemic wounds presenting at wound clinics are heterogeneous with respect to etiology, age of the wound, and other factors complicating wound healing. In addition, there are ethical challenges associated with collecting repeated biopsies from a patient to develop an understanding of the temporal dynamics of the mechanisms underlying chronic wounds. The need for a preclinical model of ischemic wound is therefore compelling. The porcine model is widely accepted as an excellent preclinical model for human wounds. A full-thickness bipedicle flap approach was adopted to cause skin ischemia. Closure of excisional wounds placed on ischemic tissue was severely impaired resulting in chronic wounds. Histologically, ischemic wounds suffered from impaired re-epithelialization, delayed macrophage recruitment and poorer endothelial cell abundance and organization. Compared with the pair-matched nonischemic wound, unique aspects of the ischemic wound biology were examined on days 3, 7, 14, and 28 by systematic screening of the wound tissue transcriptome using high-density porcine GeneChips. Ischemia markedly potentiated the expression of arginase-1, a cytosolic enzyme that metabolizes the precursor of nitric oxide l-arginine. Ischemia also induced the SOD2 in the wound tissue perhaps as survival response of the challenged tissue. Human chronic wounds also demonstrated elevated expression of SOD2 and arginase-1. This study provides a thorough database that may serve as a valuable reference tool to develop novel hypotheses aiming to elucidate the biology of ischemic chronic wounds in a preclinical setting.

Publisher

American Physiological Society

Subject

Genetics,Physiology

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