Hypertrophic scarring after burns and deep dermal injuries is as large a societal burden as it was 30 years ago. The reasons include 1) no validated animal model and 2) general use of non-specific homogenized samples of scar tissue without regard for histology or specimen age. We propose two exploratory approaches to studying hypertrophic scar that may provide relevent clinical data. First, the female, Duroc pig model of scarring was described 30 years ago but never explored in detail. We have developed a five-step method to validate the model and find that the model may be similar to hypertrophic scarring in humans. Second, the cones of skin extend from the hypodermis to the skin surface. They were described over one hundred years ago but have also been ignored. We have revisited the cones and found that they occur in the same locations that hypertrophic scar occurs thus suggesting a relationship. Hypothesis - Based on these premises we hypothesize that thick scar in the female, red Duroc pig is a valid model of hypertrophic scarring and can be used to determine whether the cones of skin are the source of profibrogenic signals or fibrosis during hypertrophic scarring.
Specific Aim #1 - To complete the validation of the female Duroc pig model of human, hypertrophic scar. We will compare mast cell counts, the presence of collagen nodules, and transmission electron microscopy studies of collagen structure in scar of the female Duroc pig to human hypertrophic scar and to the literature.
Specific Aim #2 - To determine whether gene expression patterns in cones of skin suggest a role for these structures in profibrogenic signaling or fibrosis during scarring in the female Duroc. We will laser capture microdissect cones from shallow and deep partial-thickness Duroc wounds, extract and amplify the mRNA, and perform porcine DNA array analysis to determine which genes are differentially expressed.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21GM074673-02
Application #
7140225
Study Section
Special Emphasis Panel (ZRG1-SBIB-G (02))
Program Officer
Ikeda, Richard A
Project Start
2005-08-01
Project End
2009-07-31
Budget Start
2006-08-01
Budget End
2009-07-31
Support Year
2
Fiscal Year
2006
Total Cost
$182,215
Indirect Cost
Name
University of Washington
Department
Surgery
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Engrav, Loren H; Tuggle, Christopher K; Kerr, Kathleen F et al. (2011) Functional genomics unique to week 20 post wounding in the deep cone/fat dome of the Duroc/Yorkshire porcine model of fibroproliferative scarring. PLoS One 6:e19024
Zhu, Kathy Q; Carrougher, Gretchen J; Couture, Oliver P et al. (2008) Expression of collagen genes in the cones of skin in the Duroc/Yorkshire porcine model of fibroproliferative scarring. J Burn Care Res 29:815-27
Zhu, Kathy Q; Carrougher, Gretchen J; Gibran, Nicole S et al. (2007) Review of the female Duroc/Yorkshire pig model of human fibroproliferative scarring. Wound Repair Regen 15 Suppl 1:S32-9
Harunari, Nobuyuki; Zhu, Kathy Q; Armendariz, Rebecca T et al. (2006) Histology of the thick scar on the female, red Duroc pig: final similarities to human hypertrophic scar. Burns 32:669-77