Diabetic Foot Ulcers and Epidermal Growth Factor: Revisiting the Local Delivery Route for a Successful Outcome

• Published in: BioMed research international Vol. 2017; no. 2017; pp. 1 - 10
• Main Authors: Fernández-Mayola, Maday, Pimentel-Vázquez, Eulogio, Urquiza-Rodríguez, Aleida, Kulikovsky, Moshe, Guillen Nieto, Gerardo E., García del Barco Herrera, Diana, Falcón‐Cama, Viviana, García-Ojalvo, Ariana, Mendoza-Marí, Yssel, Savigne-Gutiérrez, William, Valdés-Pérez, Calixto, Fernández-Montequín, José, Berlanga-Acosta, Jorge, Pérez-Saad, Héctor
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01-01-2017; Hindawi; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Administration, Topical; Amputation; Analysis; Angiogenesis; Bioavailability; Biochemistry; Cellular Microenvironment - drug effects; Diabetes; Diabetes mellitus; Diabetic foot; Diabetic Foot - drug therapy; Diabetic Foot - genetics; Diabetic Foot - pathology; Endothelial cells; Epidermal growth factor; Epidermal Growth Factor - genetics; Epidermal Growth Factor - therapeutic use; Epigenetics; Feet; Fibroblasts; Foot diseases; Health aspects; Humans; Hypoxia; Infiltration; Leg ulcers; Methods; Mortality; Organs; Peripheral neuropathy; Pharmacology; Pharmacovigilance; Physiological aspects; Physiology; Protein-tyrosine kinase; Proteins; Receptor Protein-Tyrosine Kinases - genetics; Review; Rodents; Topical application; Tyrosine; Ulcers; Wound healing; Wound Healing - genetics
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2017/2923759

Soon after epidermal growth factor (EGF) discovery, some in vivo models appeared demonstrating its property to enhance cutaneous wound healing. EGF was the first growth factor (GF) introduced in the clinical arena as a healing enhancer, exerting its mitogenic effects on epithelial, fibroblastoid, and endothelial cells via a tyrosine kinase membrane receptor. Compelling evidences from the 90s documented that, for EGF, locally prolonged bioavailability and hourly interaction with the receptor were necessary for a successful tissue response. Eventually, the enthusiasm on the clinical use of EGF to steer the healing process was wiped out as the topical route to deliver proteins started to be questioned. The simultaneous in vivo experiments, emphasizing the impact of the parenterally administered EGF on epithelial and nonepithelial organs in terms of mitogenesis and cytoprotection, rendered the theoretical fundamentals for the injectable use of EGF and shaped the hypothesis that locally infiltrating the diabetic ulcers would lead to an effective healing. Although the diabetic chronic wounds microenvironment is hostile for local GFs bioavailability, EGF local infiltration circumvented the limitations of its topical application, thus expanding its therapeutic prospect. Our clinical pharmacovigilance and basic studies attest the significance of the GF local infiltration for chronic wounds healing.