J Korean Med Sci.  2010 Apr;25(4):589-596. 10.3346/jkms.2010.25.4.589.

Effect of Recombinant Human Epidermal Growth Factor Against Cutaneous Scar Formation in Murine Full-thickness Wound Healing

• Kim YS
• Lew DH
• Tark KC
• Rah DK
• Hong JP

• KMID: 1792930
• DOI: http://doi.org/10.3346/jkms.2010.25.4.589

Abstract

A visible cutaneous scar develops from the excess formation of immature collagen in response to an inflammatory reaction. This study examined the role of epidermal growth factor (EGF) in the formation of cutaneous scars. Twenty Crl:CD-1 (ICR) mice were used and 2 full-thickness skin wounds were made on the dorsum of each mouse. One of the wounds was treated with recombinant human EGF by local application and the other was treated with saline for control until complete healing was achieved. The EGF-treated group's wounds healed faster than the control group's. The width of the scar was smaller by 30% and the area was smaller by 26% in the EGF-treated group. Inflammatory cell numbers were significantly lower in the EGF-treated group. The expression of transforming growth factor (TGF)-beta1 in the EGF-treated group was increased. It was observed that the amount of collagen in the EGF-treated group was larger than the control group. In the EGF-treated group, the visible external scars were less noticeable than that in the control group. These results suggest that EGF can reduce cutaneous scars by suppressing inflammatory reactions, decreasing expression of TGF-beta1, and mediating the formation of collagen.

Keyword

Epidermal Growth Factor; Cicatrix; Wound Healing

MeSH Terms

Animals
Cicatrix/pathology/*prevention & control
Collagen/metabolism
Epidermal Growth Factor/*pharmacology
Humans
Inflammation/metabolism
Mice
Recombinant Proteins/*pharmacology
Skin/drug effects/metabolism/pathology
Wound Healing/*drug effects
Recombinant Proteins
Epidermal Growth Factor
Collagen

Figure

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  Fig. 1 Time-wound area curve for degree of healing in each group shows that full-thickness wounds heal more rapidly in the EGF-treated group than the control group. Healing time (HT50) was about 5.4 days in the EGF-treated group and 7.5 days in the control group.

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  Fig. 2 Gross pictures of both wounds were taken every 3 days after full-thickness skin excision. Wound size decreases more rapidly in the EGF-treated group. POD, Post-operative day.

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  Fig. 3 Cross-sections of wounds stained with Masson's trichrome staining. Scar width and area (above the panniculus muscle) are significantly reduced in 4 weeks postoperatively in the EGF-treated group compared to the control group (×40).

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  Fig. 4 Counts of inflammatory cells. (A, B) Histopathological sections in control and EGF groups (H&E, ×100). (C) The graph shows the effect of EGF on reducing inflammatory cells (cell counts/high power field [HPF], ×400).

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  Fig. 5 Immunohistochemical observation of full-thickness wound at 4 days. The immunoactive area of TGF-β1 (brown) is markedly increased in the control group, especially in the stroma (A, C). The expression of TGF-β1 was decreased in the EGF-treated group (B, E) but increased in the adjacent normal skin area (D).

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  Fig. 6 Trichrome staining for collagen pattern in each group at 3 weeks. In the EGF-treated group, the epidermis is well established. Collagen bundles are mature, organized, and well arranged. The amount of collagen is similar to that of normal stroma. In contrast, an immature, disorganized collagen pattern is noted in the control group and the amount of collagen is smaller than that of normal stroma.

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