Acute and Chronic Animal Models for Excessive Dermal Scarring: Quantitative Studies

Abstract

Excessive scarring in the form of keloids and hypertrophic scars continues to be a clinical problem for some patients. The lack of an animal model for such scarring has been an obstacle to studying the cellular and molecular biology of these entities. Previous observations made by the authors that some surgical scars in the rabbit ear remain raised for months after wounding prompted us to investigate whether the rabbit ear might provide a model by which to study excessive dermal scarring. After establishing the model in preliminary study, 40 excisional wounds, 6 mm in diameter, were created over the ventral surface of rabbit ears. Elevated scars were treated with either intralesional triamcinolone acetonide or saline at day 16 postwounding. On day 22, 25 scar wounds were used for thorough histomorphometric analysis, 15 wounds were eliminated prior to analysis because of invagination of epithelial tissue, which made analysis difficult. Total area of scar and Hypertrophic Index, a ratio comparing scar prominence with the thickness of adjacent unwounded tissue, were measured for 25 (62 percent) of the resulting scars. Both total area of scar and Hypertrophic Index were found to be significantly decreased in the steroid-treated group (p < 0.02 and < 0.03, respectively). In a chronic form of this model, in which larger excisions were taken, an excessive accumulation of both new collagen and cartilage over 9 months was observed. An animal model for excessive dermal scarring that allows quantitation of scar formation and, at an early stage, can be modulated in a predictable way with intralesional corticosteroid treatment is presented. This model may parallel hypertrophic scarring in humans and thus might provide a tool by which to study its pathophysiology and objectively evaluate therapeutic modalities.

Silicone occlusive treatment of hypertrophic scar in the rabbit model

“…This index is the ratio of total wound area tissue height to the area of normal tissue below the hypertrophic scar. 26,27 Each wound was measured twice by a blinded examiner using a calibrated eyepiece reticule. Overall dermal cellularity was quantified by counting cells per high-power field (100=).…”

“…25 Our laboratory has developed a unique animal model of hypertrophic scarring in the rabbit ear that has been shown to be similar to the human condition in histologic and visual appearance with respect to larger wounds, response to steroids, and improvement in degree of scarring with advanced age. 26,27 Furthermore, the hypertrophy is more marked in wounds with delayed epithelialization. In this study, we used the rabbit ear hypertrophic scar model to compare the scar responses of adherent silicone gel sheeting with semiocclusive dressings, including microporous paper taping, which has been advocated as a treatment to improve scars.…”

Recombinant human endostatin reduces hypertrophic scar formation in rabbit ear model through down-regulation of VEGF and TIMP-1

“…The rabbit HS models were established according to the previous report 13 . The animals were anaesthetized with 1% (10 g/L) pentobarbital sodium (1 mg/kg), and then one hundred ninety-two wounds were created on the ventral surface of each ear by means of an 11 mm pen cover ( Figure 1).…”

LCB 03-0110, a Novel Pan-Discoidin Domain Receptor/c-Src Family Tyrosine Kinase Inhibitor, Suppresses Scar Formation by Inhibiting Fibroblast and Macrophage Activation

“…Digital images were taken at 100ϫ amplitude under a light microscope. Hypertrophic scar formation was evaluated by histomorphometric analysis following a previously described procedure (Morris et al, 1997). Each digital image was processed with Image-Pro Plus (Adobe Photoshop; Adobe Systems, San Jose, CA) to measure the total area of the new scar, which included the original tissue area before wounding and the elevated scar region over it.…”