The Temporal Effects of Anti-TGF-β1, 2, and 3 Monoclonal Antibody on Wound Healing and Hypertrophic Scar Formation

Abstract

Background A number of studies have implicated transforming growth factor (TGF)-β1, 2, and 3 (TGF-β) in wound healing and hypertrophic scarring. We propose that TGF-β has a temporal effect on these processes. To test this hypothesis, we applied anti-TGF β1, 2, and 3 monoclonal antibody topically to our dermal ulcer model in the rabbit ear. Study design Rabbit ear wounds were treated intradermally with anti-TGF-β1, 2, and 3 antibody at early, middle, and late time points. Treated and untreated control wounds were harvested at various time points and examined histologically to quantify wound healing and scar hypertrophy. Real-time polymerase chain reaction was performed to determine TGF-β mRNA expression in the treated and control wounds. Results The early treatment group demonstrated decreased new epithelium and granulation tissue (p < 0.05 versus controls). Scars harvested on days 28 and 40 displayed no difference in scar hypertrophy. Both the middle and late treatment groups demonstrated a significant decrease in scar hypertrophy (p < 0.05). Conclusions Treated wounds from the early treatment group displayed delayed wound healing, with no reduction in scar hypertrophy. Later treatment of wounds with the same antibody, beginning 7 days after wounding, resulted in a reduction in scar hypertrophy. These results support our hypothesis and clearly demonstrate that TGF-β1, 2, and 3 have differential temporal effects during the wound-healing process, and are important for optimal wound healing in the first week after wounding; beyond 1 week, TGF-β1, 2, and 3 play a critical role in hypertrophic scar formation.