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

Author:

Berlanga-Acosta Jorge1ORCID,Fernández-Montequín José2,Valdés-Pérez Calixto2,Savigne-Gutiérrez William2,Mendoza-Marí Yssel1ORCID,García-Ojalvo Ariana1,Falcón‐Cama Viviana1,García del Barco-Herrera Diana1,Fernández-Mayola Maday1,Pérez-Saad Héctor1,Pimentel-Vázquez Eulogio1,Urquiza-Rodríguez Aleida3,Kulikovsky Moshe4,Guillén-Nieto Gerardo1

Affiliation:

1. Wound Healing and Cytoprotection Research Group, Center for Genetic Engineering and Biotechnology, Ave 31 e/158 and 190, Cubanacan, Playa, P.O. Box 10600, Havana, Cuba

2. National Institute of Angiology and Vascular Surgery, Calzada del Cerro No. 1551, El Cerro, Havana, Cuba

3. Dermatology Department, Center for Surgical and Medical Research, Calle 216 y 11-B, Reparto Siboney, Playa, Havana, Cuba

4. Lin Medical Center, Rehov Vardia 12, 3465712 Haifa, Israel

Abstract

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.

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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3. Making history;Angiología;2024

4. The use of intralesional epidermal growth factor in the treatment of diabetic foot ulcers;Journal of Medicine and Palliative Care;2023-12-31

5. Advanced Drug Delivery System for Management of Chronic Diabetes Wound Healing;Current Drug Targets;2023-12

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