Abstract
Wound infections constitute an increasing clinical problem worldwide. To reverse this trend, several wound dressings with antimicrobial properties have been developed. Considering the increasing presence of antibiotic-resistant microorganisms, product developers have been focusing their efforts in introducing antibiotic-free antibacterial wound dressings to the market, with silver being the most commonly incorporated antimicrobial agent. In this scenario, gaining information about the microbial and eukaryotic cells’ response to these dressings is needed for a proper selection of antimicrobial dressings for the different cases of infected wounds. In particular, one insufficiently explored parameter is the effect of the dressings on the immunomodulation of macrophages, the main immune cell population participating in the repair process, because of their pivotal role in the transition of the inflammation to the proliferation phase of wound healing. In this work, three different clinically applied antimicrobial, silver impregnated wound dressings were selected: Atrauman® Ag, Biatain® Alginate Ag and PolyMem WIC Silver® Non-adhesive. Antimicrobial susceptibility tests (disk diffusion and broth dilution), cell viability evaluation (CellTiter-Blue®) and experiments to determine macrophage polarization (e.g., flow cytometry, ELISA and glucose uptake) were performed after 24 h of incubation. Among all products tested, Biatain® Alginate Ag induced the most evident bactericidal effect on Gram-positive and Gram-negative bacteria, followed by PolyMem WIC Silver® Non-adhesive, but did not show good cytocompatibility in vitro. On the other hand, Atrauman® Ag showed excellent cytocompatibility on L929 fibroblasts, HaCaT keratinocytes and THP-1 derived macrophages, but no significant antimicrobial activity was observed. Overall, it was confirmed that macrophages initiate, in fact, an alteration of their metabolism and phenotype in response to wound dressings of different composition in a short period of contact (24 h). M0 resting state macrophages common response to all silver-containing dressings used in this study was to increase the production of the anti-inflammatory cytokine TGF-β, which indicates an acquisition of M2-like macrophages characteristics.
Highlights
Clinicians are daily faced with the extremely difficult challenge of selecting the most appropriate dressing among those available in the market (Dhivya et al, 2015)
The antibacterial efficacy of the selected wound dressings was evaluated on four bacterial strains typically found in wound infections (S. aureus, S. epidermidis, E. coli, and P. aeruginosa) (Gjødsbøl et al, 2006; Ibberson et al, 2017)
With the colony forming units (CFU) counted after 24 h, it was possible to determine the exact reduction of CFU/mL provoked by each antimicrobial dressing
Summary
Clinicians are daily faced with the extremely difficult challenge of selecting the most appropriate dressing among those available in the market (Dhivya et al, 2015). Silver ions are known for causing the induction of an increased production of reactive oxygen species (ROS) and interaction with cytosolic components as enzymes and nucleic acids (Sütterlin et al, 2012) These dressings are not sufficiently investigated, especially concerning the effects on immunomodulation of macrophages (Krzyszczyk et al, 2018). Based on our current knowledge, the optimal wound healing stages in chronological order go through haemostasis, inflammation, proliferation and remodeling phases (Velnar et al, 2009; Krzyszczyk et al, 2018) During this process, macrophages are deeply involved, by shifting from a predominant M1 pro-inflammatory population to an antiinflammatory/tissue-remodeling M2 phenotype, while some populations might share characteristics of both M1 and M2 macrophages (Ferrante and Leibovich, 2012). M1 macrophages present augmented levels of major histocompatibility complex (MHC) cell surface receptors, known as HLA-DR, and the chemokine receptors CD197 that bind CCL19 and CCL21 (Yamane and Leung, 2016)
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