The Effect of Topically Applied Recombinant Human Growth Hormone on Wound Healing in Pigs
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A score of 1 to 5 was assigned to each parameter (1 = weakly stained, 5 = strongly stained).
Statistical evaluation. Statistical assessment of the changes in wound size and staining intensity in both groups was performed using the Wilcoxon test; P < 0.05 was considered significant.
Healing time. A significant reduction in the wound sizes of the GH-treated group was observed as compared with the control group (P < 0.05). The wound size of the experimental group decreased significantly more than the control group each week. In the later weeks, the ratio of wound area reduction between the two groups increased. The healing rate in the GH-treated group was faster than that of the control group (Figure 3).
Histological and immunohistochemical examination. To compare IGF-1 levels, the initial (week 1) biopsies of both groups were reviewed, because the healing might be most actively processed. To examine collagen production, the third week biopsies were compared because the healing process was almost finished and the collagen deposition would be most abundant.
Immunostaining for IGF-1 revealed that in GH-treated group, production of IGF-1 increased significantly more than that of the control group, meaning that locally administered GH promoted IGF-1 production within the wound.
Immunostaining for collagen 1 revealed that collagen production in the GH-treated group was greater than that of the control group. This means that locally administered GH can produce IGF-1 in the wound area, and IGF-1 can stimulate granulation tissue growth. But immunohistochemical analysis in collagen 3 showed no significant difference in staining intensity (Figures 4, 5).
The foremost role of IGF-1 is its insulin-like metabolic effects; it can stimulate the growth of target tissues such as the liver, adipose tissue, muscle, cartilage, and fibroblasts.8,9 IGF-1 can enhance protein production, cell proliferation, and migration, which is essential in the wound-healing process.15,16 IGF-1 expression is increased in subcutaneous17 and incisional18 wounds, and in post-burn injuries.19 Some studies have shown that the administration of exogenous IGF-I enhanced protein synthesis in severely burned experimental animals.20 However, recent data have demonstrated that administered IGF-1 did not improve wound healing, and only the IGF-1 produced locally by fibroblasts and macrophages contributed to the regulation of wound healing.10,11
To enhance the wound healing process, especially in chronic wounds, many growth factors were tested and are now clinically applied. If the systemic IGF-1 was ineffective in wound healing, topical administration of IGF-1 can be considered as other growth factors such as EGF, TGF-β, etc. Unfortunately, topical administration of growth factors has some shortcomings. The cost to produce growth factors is significantly high as it is difficult to keep and transport; hence, increasing IGF-1 production locally by GH administration is superior to administration of IGF-1 itself.
It has been reported that systemic application of GH has a positive effect on wound healing. Systemic GH can increase the collagen production and mechanical strength of wounds.6,21 Ghofrani et al14 reported that systemic GH could accelerate the split-thickness skin defect in pigs.
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