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Transforming growth factor beta 1 improves wound healing and random flap survival in normal and irradiated rats
A V Nall1, R E Brownlee, C P Colvin
1Department of Otolaryngology, College of Medicine, University of Florida, Gainesville, USA.
Objectives:
To evaluate the effect of chronic irradiation on wound healing and random flap survival (FV), and the effect of transforming growth factor beta 1 (TGF-beta 1) in this setting using an animal model.
Design:
A randomized, controlled study with four groups of rats to study the effect of irradiation 4 months before surgical intervention. The effect of TGF-beta 1 on FV and wound healing also was evaluated in the irradiated and nonirradiated groups.
Subjects:
Ninety-five rats were available for evaluation. Group 1 (n = 10) was the control; group 2 (n = 28) received TGF-beta 1; group 3 (n = 28) received radiation therapy; and group 4 (n = 29) received radiation therapy and TGF-beta 1.
Intervention:
The irradiated groups received 15 Gy to their dorsal skin. Four months later all received McFarlane skin flaps. Groups 2 and 4 received topical TGF-beta 1, 4 micrograms, to the bed of the flap; groups 1 and 3 received saline. On postoperative day 7 all rats were evaluated for tensile strength and FV, and histologic staining with hematoxylin-eosin for collagen and TGF-beta 1 was done. The slides were evaluated in a "blinded" fashion.
Results:
Irradiation decreased tensile strength and FV, but not to a notable degree. Transforming growth factor beta 1 improved tensile strength in the irradiated (P = .04, Student's t test) and nonirradiated groups (P = .05, Student's t test). Transforming growth factor beta 1 also improved FV in all groups, but significantly in the irradiation plus TGF-beta 1 group (P = .001, Student's t test). The TGF-beta 1 group had the most mature collagen present at the wound edge. No qualitative difference was seen in the immunohistochemical staining for the four groups.
Conclusions:
Transforming growth factor beta 1 improves wound healing and random FV in radiated and nonirradiated rat skin. Further study is needed to determine the radiation dose necessary to create an "impaired wound-healing model" in rats, and the optimum dose of TGF-beta 1 in this setting.