Polysaccharide-Based Formulations for Healing of Skin-Related Wound Infections: Lessons from Animal Models and Clinical Trials

Abstract

Skin injuries constitute a gateway for pathogenic bacteria that can be either part of tissue microbiota or acquired from the environmental. These microorganisms (such as Acinetobacter baumannii, Enterococcus faecalis, Pseudomonas aeruginosa, and Staphylococcus aureus) produce virulence factors that impair tissue integrity and sustain the inflammatory phase leading for establishment of chronic wounds. The high levels of antimicrobial resistance have limited the therapeutic arsenal for combatting skin infections. Thus, the treatment of non-healing chronic wounds is a huge challenge for health services worldwide, imposing great socio-economic damage to the affected individuals. This scenario has encouraged the use of natural polymers, such as polysaccharide, in order to develop new formulations (membranes, nanoparticles, hydrogels, scaffolds) to be applied in the treatment of skin infections. In this non-exhaustive review, we discuss the applications of polysaccharide-based formulations in the healing of infected wounds in animal models and clinical trials. The formulations discussed in this review were prepared using alginate, cellulose, chitosan, and hyaluronic acid. In addition to have healing actions per se, these polysaccharide formulations can act as transdermal drug delivery systems, controlling the release of active ingredients (such as antimicrobial and healing agents). The papers show that these polysaccharides-based formulations are efficient in controlling infection and improve the healing, even in chronic infected wounds. These data should positively impact the design of new dressings to treat skin infections.

Sulfated Polysaccharides from Marine Algae as a Basis of Modern Biotechnologies for Creating Wound Dressings: Current Achievements and Future Prospects

“…During evolution, these organisms acquired the ability to synthesize a wide range of metabolites and biomolecules, many of which have a unique chemical structure that other organisms do not have [10,[53][54][55][56]76,77]. Polysaccharides from marine algae are of particular interest due to the high resistance, biological activity, and availability of these organisms in large numbers [21,59,61,69,74].…”

“…It consists of several successive and interrelated phases: coagulation (hemostasis), inflammation, fibroblast proliferation, and tissue remodeling [23,[27][28][29][30] (Figure 1). The initial stage is aimed at preventing excessive blood loss, for which it triggers the hemostatic mechanisms in response to bleeding [19,21,24]. This phase lasts for several minutes and mainly affects the epithelial and endothelial compartments, as well as blood cells.…”

“…During this phase, the synthesis and lysis of collagen comes to equilibrium, excessive macromolecules degrade, and the cellular phenotypes and the integrity of the skin restore [11,31,[38][39][40]. The criterion for successful wound treatment is the epithelialization of the wound surface, which depends on angiogenesis occurring The initial stage is aimed at preventing excessive blood loss, for which it triggers the hemostatic mechanisms in response to bleeding [19,21,24]. This phase lasts for several minutes and mainly affects the epithelial and endothelial compartments, as well as blood cells.…”

Polyacrylamide-Metilcellulose Hydrogels Containing Aloe barbadensis Extract as Dressing for Treatment of Chronic Cutaneous Skin Lesions

“…After this period, the receptacles were removed from the oven, cooled and weighed. The result was calculated using Equation (1).…”

“…Chronic wounds are severe breaks in the skin barrier that fail to heal in an acceptable time-frame, thus preventing the complete restoration of the tissue's anatomical and functional integrity, increasing the likelihood of infections and apoptosis. Wounds become chronic if they do not pass through all the phases of healing, that include hemostasis, inflammatory, proliferative, and remodeling [1,2]. Chronic wounds are an unsuspecting epidemic that affects a large fraction of the world's population [3].…”