Diabetic foot ulceration is a major complication of diabetes mellitus. Recombinant human epidermal growth factor (rhEGF) is used topically in the treatment of diabetic foot ulcers. This meta-analysis was designed to evaluate if rhEGF increased the complete healing rate of diabetic foot compared with controls. We searched the MEDLINE, Cochrane Library, EMBASE, and Web of Knowledge databases (up to December 22, 2015). Studies were identified and selected, and data were extracted by 2 independent reviewers. A total of 4 randomized controlled trials including 294 patients were identified. The studies evaluated the rate of healing of diabetic foot that were treated with rhEGF or controls. On account of study heterogeneity, a random-effects model was performed, and the combined odds ratio (OR) indicated a significantly greater complete healing rate in patients treated with rhEGF compared to placebo. The ORs ranged from 1.66 to 14.64, with a combined OR of 4.36 (95% confidence interval = 1.48-12.81, P = .007). These results indicate that rhEGF is efficacious in the treatment of diabetic foot ulcers by increasing the rate of wound healing. These findings support the use of rhEGF in treating diabetic foot.

The majority of studies on scar formation have mainly focused on the dermis and little is known of the involvement of the epidermis. Previous research has demonstrated that the scar tissue-derived keratinocytes are different from normal cells at both the genetic and cell biological levels; however, the mechanisms responsible for the fundamental abnormalities in keratinocytes during scar development remain elusive. For this purpose, in this study, we used normal, wound edge and hypertrophic scar tissue to examine the morphological changes which occur during epidermal regeneration as part of the wound healing process and found that the histological structure of hypertrophic scar tissues differed from that of normal skin, with a significant increase in epidermal thickness. Notably, staining of the basement membrane (BM) appeared to be absent in the scar tissues. Moreover, immunofluorescence staining for cytokeratin (CK)10, CK14, CK5, CK19 and integrin-β1 indicated the differential expression of cell markers in the epidermal keratinocytes among the normal, wound edge and hypertrophic scar tissues, which corresponded with the altered BM structures. By using a panel of proteins associated with BM components, we validated our hypothesis that the BM plays a significant role in regulating the cell fate decision of epidermal keratinocytes during skin wound healing. Alterations in the structure of the BM promote basal keratinocytes to adopt a proliferative phenotype both in vivo and in vitro.

Skin wound healing is a complex event, and interrupted wound healing process could lead to scar formation. The aim of this study was to examine the morphological changes of scar tissue. Pathological staining (HE staining, Masson's trichrome staining, methenamine silver staining) was used to evaluate the morphological changes of regenerating epidermis in normal skin and scar tissue, and immunofluorescence staining to detect the expression of collagen IV, a component of basement membrane (BM), and the expression of integrinβ4, a receptor for BM laminins. Additionally, the expression of CK14, CK5, and CK10 was measured to evaluate the proliferation and differentiation of keratinocytes in normal skin and scar tissue. The results showed that the structure of the skin was histologically changed in scar tissue. Collagen IV, expressed under the epidermis of normal skin, was reduced distinctly in scar tissue. Integrinβ4, expressed in the basal layer of normal skin, was found absent in the basal layer of scar tissue. Additionally, it was found that keratinocytes in scarring epidermis were more proliferative than in normal skin. These results indicate that during the skin wound healing, altered formation of BM may affect the proliferation of keratinocytes, reepithelial and tissue remodeling, and then result in scar formation. Thus, remodeling BM structure during wound repair may be beneficial for improving healing in cutaneous wounds during clinical practice.

In the present review, we first present an overview of oriented cell division process and related proteins and molecular signals in different developmental contexts. We speculate that oriented cell division involves in epithelial polarization and skin wound healing.