Transforming Growth Factor 1 Improves Wound Healing and Random Flap Survival in Normal and Irradiated Rats

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Abstract
Objectives: To evaluate the effect of chronic irradiation on wound healing and random flap survival (FV), and the effect of transforming growth factor β1(TGFβ1) 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-β1on 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-β1; group 3 (n=28) received radiation therapy; and group 4 (n=29) received radiation therapy and TGF-β1. 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-β1, 4 μg, 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-β1was 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 β1improved tensile strength in the irradiated (P=.04, Student'sttest) and nonirradiated groups (P=.05, Student'sttest). Transforming growth factor β1also improved FV in all groups, but significantly in the irradiation plus TGF-β1group (P=.001, Student'sttest). The TGF-β1group 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 β1improves 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 woundhealing model" in rats, and the optimum dose of TGF-β1in this setting. (Arch Otolaryngol Head Neck Surg. 1996;122:171-177)

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