Evaluation of Antioxidant and Wound-Healing Properties of EHO-85, a Novel Multifunctional Amorphous Hydrogel Containing Olea europaea Leaf Extract

Abstract

The excess of free radicals in the wound environment contributes to its stagnation during the inflammatory phase, favoring hard-to-heal wounds. Oxidative stress negatively affects cells and the extracellular matrix, hindering the healing process. In this study, we evaluated the antioxidant and wound-healing properties of a novel multifunctional amorphous hydrogel-containing Olea europaea leaf extract (OELE). Five assessments were performed: (i) phenolic compounds characterization in OELE; (ii) absolute antioxidant activity determination in OELE and hydrogel (EHO-85); (iii) antioxidant activity measurement of OELE and (iv) its protective effect on cell viability on human dermal fibroblasts (HDFs) and keratinocytes (HaCaT); and (v) EHO-85 wound-healing-capacity analysis on diabetic mice (db/db; BKS.Cg-m+/+Leprdb). The antioxidant activity of OELE was prominent: 2220, 1558, and 1969 µmol TE/g by DPPH, ABTS, and FRAP assays, respectively. Oxidative stress induced with H2O2 in HDFs and HaCaT was normalized, and their viability increased with OELE co-treatment, thus evidencing a protective role. EHO-85 produced an early and sustained wound-healing stimulating effect superior to controls in diabetic mice. This novel amorphous hydrogel presents an important ROS scavenger capacity due to the high phenolic content of OELE, which protects skin cells from oxidative stress and contributes to the physiological process of wound healing.

Superiority of a Novel Multifunctional Amorphous Hydrogel Containing Olea europaea Leaf Extract (EHO-85) for the Treatment of Skin Ulcers: A Randomized, Active-Controlled Clinical Trial

“…The EHO-85 gel is a class IIb medical device in the form of an amorphous hydrogel. Among other constituents, it is composed of: Olea europaea leaf extract, due to its free radical regulation ability [ 14 ]; biosaccharide-gum 1 (an anionic polysaccharide) and glycerin, as hydrating and self-emulsifying agents; a carbomer (crosslinked acrylic acid polymer) with excellent rheological properties which contributes to provide an isolating and protective barrier for the ulcer bed; gluconolactone and sodium benzoate, included to avoid microbiological contamination; and EDTA, chosen for its antimicrobial and antibiofilm properties. The combination of these components, together with the capability of the formulation to reduce the alkalinity of the ulcer bed through its slightly acidic pH (range 5.0–5.5), gives the EHO-85 gel the ability to modulate the wound environment, thus promoting and speeding up the healing process [ 14 ].…”

“…In line with the above, supported by in vitro and in vivo studies showing its properties and mechanisms of action [ 14 ], EHO-85, a novel multifunctional amorphous hydrogel containing Olea europaea leaf extract, was developed. This new product has the moisturizing and barrier-function properties inherent to amorphous hydrogels.…”

“…The inclusion of the Olea europaea leaf extract deals with the need for a non-enzymatic ROS scavenger able to avoid the excessive and sustained increase in oxidative stress on the wound bed over time, which slows down or lead to a chronification of the healing process. Polyphenols such as those contained in the Olea europaea leaf extract, especially oleuropein, act protecting and promoting the viability of the cell types involved in the structure and regeneration of the skin, such as dermal fibroblasts and keratinocytes [ 14 ].…”

“…Cg-m +/+ Leprdb). EHO-85 treatment showed superior wound healing rates compared to standard amorphous hydrogels [ 14 ]. This would confirm the relevance of the holistic approach to wound management made possible by the novel EHO-85 gel.…”

EHO-85: A Multifunctional Amorphous Hydrogel for Wound Healing Containing Olea europaea Leaf Extract: Effects on Wound Microenvironment and Preclinical Evaluation

“…EHO-85 is composed of purified water, OELE, Fucocert ® , glycerin, Carbopol 980 ® , trieathanolamine, disodic ethylenediaminetetraacetic acid (EDTA), and Geogard ultra ® [ 39 ]. It was formulated with a slightly acidic pH (5–5.5).…”