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Agnes V. Nall, MD; Richard E. Brownlee, MD; C. Peyton Colvin, MD; Gregory Schultz, PhD; Doug Fein, MD; Nicholas J. Cassisi, DDS, MD; Tuan Nguyen; Anjay Kalra

Arch Otolaryngol Head Neck Surg. 1996;122(2):171-177.

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-β₁ 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-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-β¹ 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 β₁ improved tensile strength in the irradiated (P=.04, Student's t test) and nonirradiated groups (P=.05, Student's t test). Transforming growth factor β₁ also improved FV in all groups, but significantly in the irradiation plus TGF-β₁ group (P=.001, Student's t test). The TGF-β₁ 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 β₁ 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 woundhealing model" in rats, and the optimum dose of TGF-β₁ in this setting.

(Arch Otolaryngol Head Neck Surg. 1996;122:171-177)

Author Affiliations
From the Department of Otolaryngology, College of Medicine, University of Florida, Gainesville (Drs Nall, Brownlee, Schultz, and Cassisi, and Mr Nguyen and Ms Kalra); Georgia Head, Neck, and Facial Plastic Surgery, Dunwoody (Dr Colvin); and the Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pa (Dr Fein).

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