TGF-beta 1 alters the healing of cutaneous fetal excisional wounds

Background/Purpose: In a number of species, fetal wound healing differs fro m the adult in the absence of inflammation, fibrosis, scar formation, and e xcisional wound contraction. The lack of inflammation also may explain the relative absence of any cytokine levels at the wound site, such as transfor ming growth factor (TGF)-beta, and therefore the unique characteristics of fetal wound healing. The authors hypothesized that exogenous TGF-beta 1 wou ld induce contraction, inflammation, fibrosis, and scar formation in cutane ous excisional wounds in the feta I rabbit. Methods: Cellulose discs (3 mm in diameter) were formulated with either 1.0 mu g TGF-beta 1 (n = 6) or bovine serum albumin (BSA; n = 7), as a control , for sustained-release over 3 days. Each disc was implanted into the subcu taneous tissue on the backs of fetal New Zealand White Rabbits in utero on day 24 of gestation (term, 31 days). A full-thickness, 3-mm excisional woun d (7.4 mm(2)) was then made next to the implanted cellulose disc. All wound s were harvested 3 days later. Results: At harvest, the excisional wounds in the TGF-beta 1 group had cont racted (5.6 +/- 2.0 mm(2)), whereas those in the control group had expanded (13.5 +/- 1.2 mm(2), P < .01). The surrounding dermis in the TGF-beta 1 gr oup had 16.3 inflammatory cells per grid block compared with 12.4 cells in the control group (not significant). In addition, a greater amount of fibro sis was induced by the TGF-BI implant (1.7 +/- 0.3) than the control implan t (0.4 +/- 0.2) on a scale of 0 to 3, P < .01. In situ hybridization analys is showed an increase in procollagen type 1 alpha 1 gene expression in the surrounding dermis of the TGF-beta 1 group (36.7 +/- 3.6 grains per grid bl ock) compared with the control group (7.1 +/- 0.9 grains per grid block, P < .001). Conclusions: These results demonstrate that the cytokine TGF-beta 1 can ind uce fetal excisional wounds to contract, stimulate fibrosis, and increase p rocollagen type 1 alpha 1 gene expression. These findings further suggest t hat the absence of TGF-beta 1 at the wound site may be responsible in part for the lack of a postnatal healing response. Copyright (C) 1999 by W.B. Sa unders Company.