A skin ulcer occurs when an area of skin has broken down and the underlying tissue can be seen. Most skin ulcers occur on the lower legs or the feet. In a normal person, the skin ulcer heals quickly after the injury. However, in a person with diabetes, the healing process is impaired and takes more time even if the injury is minor.
About 1 in 6 people with diabetes develop a foot ulcer at some stage.^1,2 Such foot ulcers do not heal easily, are difficult to treat, and are more prone for serious infection. This calls for better treatment methods that address the causative problem instead of offering supportive therapy.
Over the last 10 to 15 years, a large number of trials have been performed to evaluate the safety and efficacy of growth factors in the healing of chronic wounds due to pressure (decubitus ulcers), diabetic neuropathy, and venous insufficiency.³ The greatest potential for the use of growth factors in chronic wound care is that they can accelerate healing. Growth factors work by binding to specific cell surface receptors and can target cells in a number of recognized ways or modes. After binding to receptors, growth factors can have a profound influence on cell proliferation, chemotactic activity, and extracellular matrix synthesis.⁴
Epidermal growth factor (EGF) belongs to a family of growth factors that regulate cell proliferation, migration, and differentiation through binding to receptor kinases on target cells.⁵ Epidermal growth factor has been shown to act as a mitogen and also a differentiation factor for many cell types.⁵

Mechanism of Action

Epidermal growth factor peptide induces cellular proliferation through the EGF receptor, which has a tyrosine kinase cytoplasmic domain, a single transmembrane domain, and an extracellular domain involved in EGF binding and receptor dimerization.
The proliferative effects of EGF are signaled through several pathways. Binding of EGF results in EGF receptor dimerization, autophosphorylation of the receptor, and tyrosine phosphorylation of other proteins.
Epidermal growth factor receptor activates MAP kinase pathway, ultimately causing phosphorylation of transcription factors, such as c-Fos, to create AP-1 and ELK-1 that contribute to proliferation. Activation of STAT-1 and STAT-3 transcription factors by JAK kinases in response to EGF contributes to proliferative signaling. Phosphatidylinositol signaling and calcium release induced by EGF activate protein kinase C, another component of EGF signaling.
Recombinant human epidermal growth factor (rhEGF 150 mg/g; REGEN-D™ 150, Bharat Biotech International Limited, Hyderabad, India) is a growth factor that mainly helps stimulate cell growth. The product safety study was established by conducting a complete preclinical toxicity study in rats and rabbits tested by acute, subacute, dermal, and ocular toxicity studies. The study inferred that rhEGF was safe in rats and rabbits (V.V., S.P., N.S., and G.S.R.M., unpublished data, 2002).
In the present trial, the efficacy of rhEGF 150 mg/g was evaluated in healing patients with diabetic foot ulcers.

Aim

The aim of the study was to evaluate the efficacy and safety of rhEGF gel applied topically in patients with Grade I or II (Wagner’s classification) diabetic foot ulcers and to compare the time required for complete healing of the ulcer in the test group and control group.