Sustained release of epidermal growth factor accelerates wound repair.

Abstract

Epidermal growth factor (EGF) is a potent mitogen in vitro, but its biological role is less clear. The vulnerary effects of EGF were evaluated in a model of wound repair, the polyvinyl alcohol sponge implanted subcutaneously in rats. EGF was purified to homogeneity by reverse-phase HPLC and quantified by receptor binding assay and amino acid analysis. Preliminary data showed moderate promotion of granulation tissue formation by daily injections of 10 /Ag of EGF. To test the hypothesis that long-term exposure to EGF is required for complete cellular response, the factor was incorporated into pellets releasing 10 or 20 jig of biologically active EGF per day, and the pellets were embedded within the sponges. Slow release of EGF caused a dramatic increase in the extent and organization of the granulation tissue at day 7, a doubling in the DNA content, and 33% increases in protein content and wet weight, as compared with placebo controls. Although collagen content was also increased by almost 50%, the relative rate of collagen synthesis remained the same, suggesting that the morphological and biochemical increase in coflagen resulted from increased numbers of fibroblasts rather than a specific stimulation of collagen synthesis. These results indicate that the local sustained presence ofEGIF accelerates the process of wound repair, specifically neovascularization, organization by fibroblasts, and accumulation of collagen.Epidermal growth factor (EGF) stimulates a variety of biological phenomena, including proliferation of skin and corneal epithelia in organ culture, proliferation and differentiation of epidermis and corneal epithelial cells in vivo (1), neoangiogenesis in the rabbit cornea (2), and the synthesis of DNA, RNA, protein, and hyaluronic acid in various cell lines in culture (1). Many cell types, including dermal fibroblasts, possess EGF surface receptors and will proliferate in response to EGF in cell culture (3). By contrast to the many observations in vitro, the function of growth factors during wound repair is not clear. This is in part the result of the difficulty of delivering growth factors and quantifying the responses to them in vivo.The process of healing surface wounds includes reepithelization, neovascularization, granulation tissue development, collagen elaboration, maturation and remodeling of the scar, and contraction (4). During the early phases of repair, the local accumulation of collagen strongly correlates with the accretion of tensile strength (5); hence, measuring the content and concentration of collagen at a repair site permits an estimate of the rate of healing.

Enhancement of epidermal regeneration by biosynthetic epidermal growth factor.

“…of Surgery, personal communication) using EGF topically for the treatment of partialthickness wounds. Also, Buckley et al (10) recently reported that sustained release of EGF from subcutaneous pellets accelerated processes of wound repair in rats, whereas daily injections of EGF were much less effective. In an earlier study of full-thickness wound healing, Franklin and Lynch (11) applied mouse EGF in a water-miscible ointment to full-thickness wounds in rabbit ears and reported a qualitative enhancement of wound healing.…”

Intralesional Human Recombinant Epidermal Growth Factor for the Treatment of Advanced Diabetic Foot Ulcer: From Proof of Concept to Confirmation of the Efficacy and Safety of the Procedure

“…The need for a prolonged interaction between EGF and its receptor to achieve a significant granulation tissue response in controlled wounds in mice had been reported (Buckley et al, 1985). Proteolysis exerted by the wound-derived exudate was observed incubating the ulcers´ material at neutral pH with a fluorescent-synthetic peptide at room temperature.…”

Type 2 Diabetes Mellitus (T2DM): Biological Overview from Pathways to Organelles and its Translation toward a Torpid Wound Healing Process

“…In other words, these authors demonstrated that growth factors downward diffusion is actually hindered by a number of physical and chemical factors; thus becoming limitedly available for the responsive cells. It is noteworthy to mention that according to classic studies, the interaction between EGF and its receptor requires a prolonged time window interaction in order to commit wound cells for proliferation [132]. These ideas along with the animal experiences described below provided the rationale of the intralesional delivery via local infiltration.…”