TRANSFORMING GROWTH-FACTOR-BETA IMPROVES HEALING OF RADIATION-IMPAIRED WOUNDS

Exogenously applied TGF-beta-1 has been shown to increase wound strength in incisional wounds early in the healing process. An impaired wound healing model was first established in guinea pigs by isolating flaps of skin and irradiating the flaps to 15 Gray in one fraction using a 4-MeV linear accelerator. Incisions made 2 d after irradiation were excised 7 d later, and showed decreased linear wound bursting strength (WBS) as compared to non-irradiated control wounds on the contralateral side of each animal (p = 0.001). The effect of TGF-beta on healing of radiation-impaired wounds was studied using this model. Skin on both left and right sides of guinea pigs was irradiated as above. A linear incision was made in each side. Collagen with either 1, 5, or 20-mu-g of TGF-beta was applied to one side prior to closure with staples, whereas the contralateral side received saline in collagen. Wounds given either 1 or 5-mu-g of TGF-beta were found to be stronger than controls at 7 d (p < 0.05), whereas those receiving the higher 20-mu-g dose were weaker than controls (p < 0.05). Thus, TGF-beta in lower doses improved healing at 7 d but very large amounts of the growth factor actually impaired healing. In situ hybridization done on wound samples showed increased type I collagen gene expression by fibroblasts in wounds treated with 1-mu-g TGF-beta over control wounds. These results indicate that TGF-beta improved wound healing as demonstrated by increased WBS. This improvement is accompanied by an up-regulation of collagen gene expression by resident fibroblasts.