The role of transforming growth factor-beta in the conversion from "scarless" healing to healing with scar formation.

The objective of this study was to elucidate mediators responsible for conversion of "scarless" wound healing seen in wounded, day 14 fetal mouse limbs to healing with scar formation seen in wounded, day 18 fetal mouse limbs. Wounded, day 14 limbs were grown in a serum-free organ culture system in which either phosphate-buffered saline solution or human recombinant transforming growth factor beta-1 (1 microg/ml) was added daily. Wounded, day 18 limbs were also maintained in the same organ culture system with either phosphate-buffered saline solution or neutralizing antibody to transforming growth factor-beta (1 microg/ml) treatment. Limb cross sections were examined qualitatively with Masson's Trichrome stain and quantitatively by spectrophotometric analysis of Sirius Red and Fast Green dyes which bind to collagen and noncollagenous protein, respectively. Both qualitative and quantitative analyses showed the following: there was greater collagen deposition in day 18 versus day 14 limbs by 7 days after wounding, scar formation in day 18 limbs was attenuated by the addition of anti-transforming growth factor-beta, and there was the addition of transforming growth factor-beta-augmented collagenous scar formation in wounded regions of day 14 limbs. These results strongly suggest that transforming growth factor-beta present in the local wound environment is, at least in part, responsible for the conversion of "scarless" healing occurring in wounded, day 14 limbs to scar formation present in wounded, day 18 limbs.