Myofibroblast induction with transforming growth factor-beta(1) and -beta(3) in cutaneous fetal excisional wounds

Background/Purpose: In a noncontractile fetal rabbit model, the authors rec ently have shown the induction of excisional wound contraction with sustain ed-release cellulose implants formulated with transforming growth factor (T GF)-beta. The purpose of this study was to test the hypothesis that the exc isional wound contraction in this model is associated with the induction of myofibroblasts in the surrounding dermis, demonstrated by the presence of alpha-smooth muscle actin. Methods: Cellulose discs were formulated with either 1.0 mu g of TGF-beta(1 ) (n = 6); 1.0 mu g of TGF-beta(3) (n = 9); 10 mu g of TGF-beta(3) (n = 6); or their carrier protein, bovine serum albumin (BSA; n = 9), for sustained -release over 5 days. Each disc was implanted into a subcutaneous pocket on the back of a fetal New Zealand White rabbit in utero on day 24 of gestati on (term, 31 days). A full-thickness, 3-mm excisional wound (7.4 mm(2)) was then made next to the implanted cellulose disc. All fetuses were harvested at 3 days. The amount of alpha-smooth muscle (SM) actin in the dermis arou nd the implants and wounds was determined using immunohistochemical techniq ues. Results: Excisional wounds exposed to 1.0 mu g of TGF-beta(1) (5.6 +/- 2.0 mm(2)), 1.0 mu g of TGF-beta(3) (6.9 +/- 1.0 mm(2)), and 10 mu g of TGF-bet a(3) (2.7 +/- 1.0 mm(2)) were significantly smaller when compared with the BSA control group (12.8 +/- 1.1 mm(2); P<.05). Furthermore, there was a sig nificant increase in staining for alpha-SM actin in the TGF-beta(1) (1.8 +/ - 0.5) and 10 mu g TGF-beta(3) (2.8 +/- 0.2) groups in comparison with the scant staining in the BSA control group (0.5 +/- 0.2; P<.05). Conclusions TGF-beta(1) and -beta(3) induce alpha-SM actin and contraction of cutaneous excisional wounds in a fetal noncontractile model. This model of inducible cutaneous excisional wound contraction may be useful in furthe r determining the role of the myofibroblast in wound contraction and the ph ysiology underlying this poorly understood aspect of wound healing. J Pedia tr Surg 35:183-188. Copyright (C) 2000 by W.B. Saunders Company.