030 A Rabbit Ear Excessive Scarring Model Using Growth Factor Stimulators

Abstract

Research on abnormal scarring, such as excessive scars, has been hampered by the lack of relevant animal models. Recent studies suggest that TGF‐β1, PDGF‐BB and FGF‐2 are stimulators of fibrosis or scarring. We developed a rabbit ear cutaneous excessive scarring model using the growth factor stimulators TGF‐β1 (0.25, 0.5 or 1 μg per wound), PDGF‐BB (1, 2 or 3 μg per wound) and FGF‐2 (0.5, 1, 3 or 5 μg per wound). Three 8‐mm diameter wounds were created on each ear in NZW rabbits (n = 6 wounds). The test growth factors were injected intradermally immediately after wounding. Controls consisted of PBS, BSA and wounding only without injections. Scar thickness of wounds was measured with a micrometer at days 14 and continued twice a week thereafter until sacrifice at day 28. Results showed that the greatest measurement of elevated scars was observed at day 14. Significant differences of scar thickness were observed in TGF‐β1 at a dose of 0.25 μg, PDGF‐BB at a dose of 3 μg, and FGF‐2 at a dose of 3 μg per wound groups when compared to PBS and wounding only groups (p < 0.05). Interestingly, BSA, a protein stabilizer for TGF‐β1 and FGF‐2 proteins, also significantly elevated scar thickness at day 14 over PBS alone (p < 0.05). Trichrome stained tissue sections on day 28 showed an increase in cellularity and thicker epithelium in all doses of TGF‐β1, PDGF‐BB and FGF‐2 protein treated groups when compared to wounding only, PBS or BSA treatments. In general, FGF‐2 treated wounds showed more vascularity than TGF‐β1 and PDGF‐BB treated wounds. By contrast, PDGF‐BB treated wounds showed richer collagen deposition than TGF‐β1 and FGF‐2 treated wounds. Results from these studies demonstrated that TGF‐β1, PDGF‐BB and FGF‐2 contributed to the scar formation in the rabbit ear scar model. BSA may contribute in stimulating scar formation in the early stage of wound healing in this model. Enhancing elevated scar formation in the rabbit ear model will be useful in evaluating anti‐scarring agents for excessive scars such as hypertrophic scars and keloids.