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Synthetic TGF-ß antagonist promotes healing of injured epithelial surfaces.

18586 Background: Cancer treatment often results in injury to epithelial surfaces. These injuries are often symptomatic and can delay or prevent further treatment. Since transforming growth factor-1 (TGF-ß) mediates inflammation, fibrosis, and epithelial mitogenesis, agents modulating TGF-ß may be useful in treating such wounds. We synthesized a dodecapeptide containing the active site of human TGF-ß. It is a TGF-ß antagonist in vitro. We investigated whether application to cutaneous wounds might promote epithelialization and decrease scarring by directly blocking local TGF-ß activity.


METHODS
We applied synthetic TGF-ß antagonist (1.5 mM in gel carrier, topically), with gel-only and no-treatment controls, to 6 standardized thermal burn wounds in each of 4 pigs. Wounds were measured and photographed for 41 d., then excised. Wound dimensions and percent epithelialization were calculated from photographs. Scar volume was estimated as surface area (photographs) x depth (microscopy). Statistical analysis employed student's t-test. Additional experiments utilized skin excision wounds in rabbits and pigs. Recombinant TGF-ß and platelet-derived growth factor (PDGF) were applied to identical wounds in other pigs and rabbits in parallel experiments as additional controls.


RESULTS
In TGF-ß antagonist-treated pig burn wounds, epithelialization was complete on d. 26 ± 2 (mean ± SD); control wounds were 70 ± 10% re-epithelialized by d. 26 (p < 0.001). Contraction rate, collagen and fibronectin content, and scar volume were all significantly less in treated wounds. TGF- ß and PDGF each retarded wound epithelialization.


CONCLUSIONS
Treatment of standard skin wounds with a synthetic TGF-ß antagonist promotes epithelialization in a whole-animal model. This agent may be useful in human epithelial injuries due to chemotherapy or radiation. No significant financial relationships to disclose.