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Ossabaw Pigs As A Natural Preclinical Model Of Metabolic Syndrome Mediated Impaired Wound Healing
Nandini Ghosh, Mithun Sinha, Amitava Das, Sashwati Roy, and Chandan K Sen
Indiana University
2019-02-15
Presenter: Nandini Ghosh
Affidavit:
I certify that the material proposed for presentation in this abstract has not been published in any scientific journal or previously presented at a major meeting
Director Name: Chandan K. Sen
Author Category: Other Specialty Resident
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
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. 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 made 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. The HFD Ossabaw pigs developed pre-MetSyn symptoms including dyslipidemia, abdominal obesity and high blood pressure. In HFD pigs, the wounds showed increased expression of adipocyte marker perilipin in the granulation tissue. HFD pigs 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). HFD pigs showed reduced collagen levels and fibroblast marker, FSP1, in their wound which are characteristics of disorganized granulation tissue. Further HFD pigs showed significantly reduced rete ridge in wounds (n=5, p<0.05) predicting compromised biomechanical properties of the repaired skin. We therefore propose that specific mechanisms of cutaneous wound healing were compromised in HFD Ossabaw pigs which are comparable to clinical outcomes. Thus this model offers an outstanding opportunity to study the cellular and molecular bases of healing outcomes in metabolic syndrome like obesity.
