The Effect of Topically Applied Recombinant Human Growth Hormone on Wound Healing in Pigs
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Abstract: The beneficial wound healing effect of the systemic growth hormone (GH) mediated by insulin-like growth factor 1 (IGF-1) has been widely reported. Recent studies have suggested that GH facilitates wound healing not by circulating IGF-1, but by local IGF-1 produced in the wound itself. The aim of this study was to define whether the locally administered GH could accelerate the wound-healing rate. Full-thickness skin defects (diameter 4 cm) were made in the back of micropigs, and GH (2.5 IU/L) was applied every other day for 3 weeks (11 times total). Control wounds were given the vehicle only. The wound sizes were measured weekly by planimetry and biopsies were taken. The wound sizes were significantly reduced in the GH-treated groups as compared with the control group (P < 0.05) each week. Histological and immunohistochemical examination revealed that the production of IGF-1 and collagen 1 in the experimental group increased more than in the control group. The present results suggest that local treatment with GH effectively accelerates wound healing.
Address correspondence to:
Sang Woo Lee, MD
Department of Plastic and Reconstructive Surgery
Seoul National University, Bundang Hospital
166 Gumiro, Bundang, Seongnam, Gyeonggi
Phone: +82 11 264 0674
Recombinant growth hormone (GH) has been used as an anabolic treatment in burn and postoperative patients.1,2 More recently, growth hormone has been increasingly used in experiments and has shown promise in the acceleration of wound healing in several studies.3,4 Growth hormone stimulates granulation tissue formation, increases collagen deposition, and facilitates epithelialization.5,6 It can also accelerate donor site healing in patients with burns3 and bone healing.7
Many studies have shown that insulin-like growth factor-1 (IGF-1) mediates the action of GH in wound healing. However, it has not yet been determined whether IGF-1 affects the wound through endocrine action or through paracrine and autocrine action. In the past, it was discovered that GH could have a positive effect on wound healing by stimulating the production of IGF-1 in the liver to increase circulating IGF-1 concentration.8,9 More recently, many evidences have been reported that circulating IGF-1 does not affect the wound, but that IGF-1 produced locally by fibroblasts, macrophages, and endothelial cells contribute to wound healing.10,11 And topically applied GH increases the concentration of IGF-1 mRNA in the granulation tissue in vivo.12
If the effect of IGF-1 by GH on wound healing is produced locally within the wound, then topical administration of GH can facilitate wound healing. The present study tested the contribution of topically applied GH on wound healing.
Materials and Methods
Recombinant human growth hormone and other ingredients for cream formulation were obtained from LG Household & Health Care Ltd (Seoul, Korea). White petrolatum, cod-liver oil, glycerin, bisabolol, and propylparaben were used to formulate a GH cream base. To yield 2.5 IU/L of GH cream, GH powder was dissolved in warm water and then mixed with the other ingredients.
GH concentration. The concentration of GH was determined through a preliminary study. Growth hormone stimulates fibroblast proliferation, which is an integral step in the wound healing process.13 When GH was applied, the fibroblast proliferation increased significantly (P < 0.05; paired t-test). Cell proliferation was measured by tetrazolium-based colorimetric assay (MTT cell growth assay kit, Millipore, Temecula, Calif).
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