Original Article

Journal of Investigative Dermatology (1991) 97, 430–434; doi:10.1111/1523-1747.ep12481258

Transforming Growth Factor-bold beta Improves Healing of Radiation-Impaired Wounds

Eric F Bernstein1,2, Leonidas Harisiadis1,3, Gary Salomon4, Jeffrey Norton4, Stephan Sollberg5, Jouni Uitto5, Eli Glatstein1, Joseph Glass1, Thomas Talbot6, Angelo Russo1 and James B Mitchell1

  1. 1Radiation Oncology Branch, National Institutes of Health, Bethesda, Maryland, U.S.A.
  2. 2Hahnemann University Division of Dermatology, Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A.
  3. 3George Washington University Medical Center, Washington, D.C., U.S.A.
  4. 4Surgery Branch, National Institutes of Health, Bethesda, Maryland, U.S.A.
  5. 5Department of Dermatology, Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A.
  6. 6BMEIB, National Institutes of Health, Bethesda, Maryland, U.S.A.

Received 13 February 1991; Accepted 25 April 1991.

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Abstract

Exogenously applied TGF-beta1 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 mug 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 mug of TGF-beta were found to be stronger than controls at 7 d (p < 0.05), whereas those receiving the higher 20-mug 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 mug 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.

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