Development of Alginate–Guar Gum Membranes Loaded with (−)-Epicatechin for the Treatment of Second-Degree Burn Wounds

Abstract

Introduction

The treatment of second-degree burns represents a significant clinical challenge due to the loss of skin barrier function, excessive exudate production, increased risk of infection, and disruption of normal tissue repair processes. Because conventional wound dressings primarily act as passive barriers with limited capacity to simultaneously manage exudate, maintain an adequate moist environment, and prevent microbial colonization, there is growing interest in the development of advanced dressings based on sustainable biomaterials capable of integrating moisture control, fluid absorption, and localized delivery of bioactive compounds. In this context, (−)-epicatechin is a promising molecule due to its antioxidant, anti-inflammatory, and antimicrobial properties, as well as its potential for wound-healing applications.

Objective

To design and optimize an alginate–guar gum membrane loaded with (−)-epicatechin for its potential application as a bioactive wound dressing for second-degree burn wounds.

Methodology

Membranes were developed using a Box–Behnken experimental design to evaluate the effect of guar gum, plasticizer, and CaCl₂ concentrations on critical parameters for the treatment of highly exudative wounds, including water vapor transmission rate (WVTR), swelling capacity, Young’s modulus, and hydrolytic degradation. The lead formulation was selected through a multivariable optimization strategy based on desirability functions. Subsequently, different concentrations of (−)-epicatechin were evaluated in terms of antimicrobial activity and cytocompatibility to determine the optimal loading of the bioactive compound.

Results

Analysis of the biomembranes identified the plasticizer as the factor with the greatest influence on overall membrane performance, whereas CaCl₂ exerted a predominant effect on swelling behavior and structural stability. Among the 27 formulations developed, formulation F14 exhibited the highest global desirability (D > 0.80), with a WVTR of 2100 g·m⁻²·day⁻¹ and a swelling capacity of 970%, values compatible with the requirements of dressings intended for highly exudative wounds. Furthermore, the membrane demonstrated adequate mechanical performance and controlled hydrolytic degradation, desirable characteristics for maintaining structural integrity throughout the wound-healing process. UV-C sterilization did not induce relevant alterations in the physicochemical properties of the system. A concentration of 2 wt% (−)-epicatechin was selected as optimal, providing the best combination of antimicrobial activity and biocompatibility against several microbial agents, including S. aureus, P. aeruginosa, E. coli, A. baumannii, and Candida albicans. Cytocompatibility assays performed on human BJ fibroblasts using the Alamar Blue assay demonstrated high cell viability (>85%), confirming the biological compatibility of the developed system.

Conclusions

The integration of rational design, multivariable optimization, and functionalization with (−)-epicatechin enabled the development of a bioactive membrane as a promising candidate for advanced wound dressing applications, exhibiting physicochemical and biological properties compatible with the treatment requirements of second-degree burn wounds.