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Ossabaw Pigs As A Natural Preclinical Model Of Metabolic Syndrome Mediated Impaired Wound Healing
Mithun Sinha1, Nandini Ghosh2, Shomita Steiner1, Amitava Das1, Savita Khanna1, Daniel J. Wozniak2, Sashwati Roy1, Chandan K. Sen1.
1Indiana University, Indianapolis, IN, USA, 2The Ohio State University, Columbus, OH, USA.

Background: Infected chronic wounds in the metabolic syndrome (MetSyn) patients represent a major public health burden. The current study recognizes Ossabaw swine as a powerful pre-clinical experimental model to study mechanisms of impaired wound healing under conditions of metabolic syndrome.

Objective: To study wound healing in high fat diet induced MetSyn model of Ossabaw pigs.

Methods: Ossabaw pigs (n=20) were fed either high fat diet (HFD; n=15) or standard chow (n=5) for 8 months. Following 8 months of diet, full thickness (2”x2”) excisional wounds were done on the dorsum of the pigs that were infected with 108 cfu/ml of mixed species of Pseudomonas aeruginosa PA01, Staphylococcus aureus USA300 and Acinetobacter baumannii 19606 strains. The infected wounds were followed up to day 31 post-wounding.

Results: The HFD Ossabaw pigs developed pre-MetSyn symptoms including dyslipidemia, abdominal obesity and high blood pressure. In HFD pigs, the wounds associated void space was filled with adipose tissue. Further, they showed increased expression of adipocyte marker perilipin in the granulation tissue. Pigs on HFD showed exaggerated and persistent inflammation in their wounds. HFD pigs showed lower abundance of endothelial cells in the granulation tissue pointing towards impaired vascularization (n=5, p<0.05). Masson's trichrome staining of the wound bed showed reduced collagen levels in HFD pigs. Reduced levels of fibroblast marker, FSP1, in HFD pigs is characteristics of disorganized granulation tissue. The length of rete ridge were significantly reduced in the repaired skin of HFD pigs (n=5, p<0.05) predicting compromised biomechanical properties of the repaired skin. Conclusion: HFD induced MetSyn in Ossabaw pigs with characteristics comparable to clinical outcomes. Specific mechanisms of cutaneous wound healing were compromised in HFD Ossabaw pigs. Thus this model offers an outstanding opportunity to study the cellular and molecular bases of healing outcomes in metabolic syndrome like obesity.

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