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A significant impediment to studying hypertrophic scar is the lack of an animal model. We have confirmed similarities between scarring in the female red Duroc pig (FRDP) and human hypertrophic scar and conclude that this model warrants validation. Reports have suggested that the cutaneous nervous system may play a role in hypertrophic scar development and several studies have shown nerve density in hypertrophic scar to be increased. The purpose of this study was to further validate the FRDP model of hypertrophic scar by quantifying nerves in FRDP tissue and comparing the findings to human hypertrophic scar. Wounds of varying depth were created on the backs of two FRDP and tissue samples were harvested at 10 days, 1 month and 5 months post-wounding. Human specimens were obtained from six burn patients. Immunohistochemistry was performed and digital images were captured. Color subtractive computer-assisted image analysis was used to quantify nerve density and nerve area fraction. The results demonstrate that nerve tissue is increased in FRDP scar tissue and is quite similar to that in human hypertrophic scar and to that described in the literature. These data provide additional evidence that the FRDP model may be useful for studying hypertrophic scarring.

Abstract: Despite decades of research, our understanding of human hypertrophic scar is limited. A reliable animal model could significantly increase our understanding. We previously confirmed similarities between scarring in the female, red, Duroc pig and human hypertrophic scarring. The purpose of this study was to: (1) measure vascular endothelial growth factor (VEGF) and nitric oxide (NO) levels in wounds on the female Duroc; and (2) to compare the NO levels to those reported for human hypertrophic scar. Shallow and deep wounds were created on four female Durocs. VEGF levels were measured using ELISA and NO levels with the Griess reagent. VEGF and NO levels were increased in deep wounds at 10 days when compared to shallow wounds (p < 0.05). At 15 weeks, VEGF and NO levels had returned to the level of shallow wounds. At 21 weeks, VEGF and NO levels had declined below baseline levels in deep wounds and the NO levels were significantly lower (p < 0.01). We found that VEGF and NO exhibit two distinctly different temporal patterns in shallow and deep wounds on the female Durocs. Furthermore, NO is decreased in female, Duroc scar as it is in human, hypertrophic scar further validating the usefulness of the model. [Copyright &y& Elsevier]

Knowledge of the pathophysiology of hypertrophic scarring following deep dermal injuries is minimal due to the lack of an animal model. We previously confirmed that thick scars in female, red Duroc pigs (FRDP) are similar to human hypertrophic scar. The purpose of this study was to evaluate TGFβ1, IGF-1, decorin, and versican expression in FRDP wounds. Deep and shallow wounds on the backs of two FRDPs were studied over 5 months. Immunohistochemistry was performed for TGFβ1, IGF-1, decorin, and versican. TGFβ1 and IGF-1 mRNA were evaluated by in situ hybridization and RT-PCR. In shallow wounds (1) TGFβ1 protein was not detectable and IGF-1 protein was seen at 10 days post-wounding. TGFβ1 and IGF-1 mRNA were elevated for 30 days. (2) Decorin protein was not detected at 10th day, but returned to levels of uninjured skin. (3) Versican protein was not detectable at any time. In deep wounds, (1) TGFβ1 and IGF-1 protein and mRNA were elevated early, (2) decorin protein was greatly reduced for the first 90 days, and (3) versican protein was present from 30 to 150 days. These findings correlate with findings reported in the literature for human hypertrophic scar and further validate the FRDP model of hypertrophic scarring. [Copyright &y& Elsevier]

Abstract: The etiology and treatment of hypertrophic scar remain puzzles even after decades of research. A significant reason is the lack of an accepted animal model of the process. The female, red Duroc pig model was described long ago. Since the skin of the pig is similar to that of humans, we are attempting to validate this model and found it to be encouraging. In this project we quantified myofibroblasts, mast cells and collagen nodules in the thick scar of the Duroc pig and compared these to the values for human hypertrophic scar. We found the results to be quite similar and so further validated the model. In addition, we observed that soon after wounding an inflammatory cell layer forms. The thickness of the inflammatory layer approaches the thickness of the skin removed as if the remaining dermis “knows” how much dermis is gone. In deep wounds this inflammatory layer thickens and this thickness is predictive of the thickness of the ultimate scar. [Copyright &y& Elsevier]