The Effects of Topical Transforming Growth Factor-β2 and Anti-Transforming Growth Factor-β2,3 on Scarring in Pigs

Abstract

Background: Transforming growth factor-β2 (TGF-β2) has been implicated in the inflammatory response and subsequent scarring during wound healing. Objective: The experiment was designed to study the effects of a topical application of TGF-β2 and mouse monoclonal anti-TGF-β2,3 neutralizing antibody (and TGF-β2,3) on the development of fibrosis during healing. Methods: Sixteen full-thickness excision wounds were made in the paravertebral and thoracic area of four domestic pigs. On day 0, three wounds each were treated with: a) 5 μg of TGF-β2, b) 5 μg of 2% methylcellulose (mc), or c) 1.2 mg of anti-TGF-β2,3. As a vehicle for treatment of each wound methylcellulose 2% was used. Four wounds served as the untreated air-exposed control. Wounds were biopsied and the tissue sectioned and stained with hematoxylin and eosin on days 7, 14, and 45. Three blinded observers evaluated the wound specimens. Results: Using computer-aided point count stereology on days 7, 14, and 45, we found a statistically significant increase (p < .05) in the number of nucleated cells in the TGF-β2-treated wounds as compared to the other control wounds. Wounds treated with anti-TGF-β2,3 had significantly (p < .05) fewer nucleated cells on days 7,14, and 45. Microscopically, the TGF-β2-treated wounds had a larger scar area as compared to anti-TGF-β2,3 and controls. Conclusion: Treating wounds with an antibody directed against TGF-β2 might be a useful clinical approach to reduce fibrosis.