Varela Patrícia, Marlinghaus Lennart, Sartori Susanna, Viebahn Richard, Salber Jochen, Ciardelli Gianluca
Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy.
Department of Experimental Surgery, Universitätsklinikum Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, Bochum, Germany.
Front Bioeng Biotechnol. 2020 Feb 25;8:124. doi: 10.3389/fbioe.2020.00124. eCollection 2020.
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 . 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.
伤口感染在全球范围内正成为一个日益严重的临床问题。为扭转这一趋势，已研发出几种具有抗菌特性的伤口敷料。鉴于抗生素耐药微生物的日益增多，产品开发者一直致力于将不含抗生素的抗菌伤口敷料推向市场，其中银是最常用的抗菌剂。在这种情况下，为针对不同类型的感染伤口正确选择抗菌敷料，需要了解微生物和真核细胞对这些敷料的反应。特别是，一个尚未充分探索的参数是敷料对巨噬细胞免疫调节的影响，巨噬细胞是参与修复过程的主要免疫细胞群体，因为它们在伤口愈合从炎症阶段向增殖阶段的转变中起关键作用。在这项研究中，选择了三种临床上常用的含银抗菌伤口敷料：爱无痕银敷料、藻酸盐银离子水胶体敷料和聚膜银离子非粘性伤口敷料。在孵育24小时后进行了抗菌药敏试验（纸片扩散法和肉汤稀释法）、细胞活力评估（CellTiter - Blue法）以及确定巨噬细胞极化的实验（如流式细胞术、酶联免疫吸附测定和葡萄糖摄取实验）。在所有测试产品中，藻酸盐银离子水胶体敷料对革兰氏阳性菌和革兰氏阴性菌均表现出最明显的杀菌效果，其次是聚膜银离子非粘性伤口敷料，但细胞相容性不佳。另一方面，爱无痕银敷料对L929成纤维细胞、HaCaT角质形成细胞和THP - 1衍生的巨噬细胞表现出优异的细胞相容性，但未观察到显著的抗菌活性。总体而言，证实了巨噬细胞实际上会在短时间接触（24小时）不同成分的伤口敷料后启动其代谢和表型的改变。本研究中使用的所有含银敷料对处于M0静息状态巨噬细胞的共同作用是增加抗炎细胞因子转化生长因子 -β的产生，这表明巨噬细胞获得了M2样巨噬细胞的特征。
