Exploring multielement nanogranular coatings to forestall implant-related infections

As we approach the post-antibiotic era, the development of innovative antimicrobial strategies that carry out their action through non-specific mechanisms could limit the onset and spread of numerous drug resistance traits among clinical isolates. In this context, the use of multielement nanogranular NPs conjugated to the surface of implantable biomaterials might represent a strategy to reduce the systemic drawbacks by locally confining the NPs effects against either prokaryotic or eukaryotic cells. In the present study, two new multielement nanogranular coatings composed of different mixtures of Ti/Mg, Ag and Cu were synthesized and tested against pathogens isolated from periprosthetic joint infections to address their potential antimicrobial value in an <em>in vitro</em> experimental setting. Overall, <em>Staphylococcus aureus</em>, <em>Staphylococcus epidermidis</em> and <em>Escherichia coli</em> displayed a significantly decreased adhesion when cultured on Ti-Ag-Cu and Mg-Ag-Cu coatings compared to uncoated controls, regardless of their antibiotic resistance traits. A dissimilar behavior was observed when <em>Pseudomonas aeruginosa</em> was cultured for 30 and 120 minutes upon the surface of Ti-Ag-Cu and Mg-Ag-Cu-coated discs. Biofilm formation was mainly reduced by the active effect of Mg-Ag-Cu compared to Ti-Ag-Cu and, again, coatings had a milder effect on <em>P. aeruginosa</em>, probably due to its exceptional capability of attachment and matrix production. These data were further confirmed by the evaluation of bacterial colonization on nanoparticles-coated discs through confocal microscopy. Finally, to exclude any cytotoxic effects on eukaryotic cells, the biocompatibility of NPs-coated discs was studied. Results demonstrated a viability of 95.8% and 89.4% of cells cultured in the presence of Ti-Ag-Cu and Mg-Ag-Cu discs, respectively, when compared to negative controls. In conclusion, the present study demonstrated the promising anti-adhesive features of both Ti-Ag-Cu and Mg-Ag-Cu coatings, as well as their action in hampering the biofilm formation, highlighting the safe use of the tested multi-element families of nanoparticles as new strategies against bacterial attachment to the surface of biomedical implants.随着我们步入后抗生素时代，开发通过非特异性机制发挥作用的新型抗菌策略，或可限制临床分离株中多种耐药性状的出现与传播。在此背景下，将多元素纳米粒（multielement nanogranular NPs）结合至可植入生物材料表面的策略，或可通过将纳米粒的作用局限于局部以对抗原核或真核细胞，从而减轻全身不良反应。本研究合成了两种由不同比例Ti/Mg、Ag与Cu混合而成的新型多元素纳米粒涂层，并针对从假体周围关节感染分离得到的病原菌开展测试，以探究其在体外（in vitro）实验环境中的潜在抗菌价值。总体而言，与未涂层对照组相比，在Ti-Ag-Cu及Mg-Ag-Cu涂层上培养的金黄色葡萄球菌（Staphylococcus aureus）、表皮葡萄球菌（Staphylococcus epidermidis）与大肠埃希菌（Escherichia coli）的黏附水平均显著降低，且与其自身耐药性状无关。而在Ti-Ag-Cu及Mg-Ag-Cu涂层圆盘上培养30分钟与120分钟的铜绿假单胞菌（Pseudomonas aeruginosa）则表现出不同的行为模式。与Ti-Ag-Cu涂层相比，Mg-Ag-Cu涂层主要通过其活性作用抑制生物膜形成；且同样地，两种涂层对铜绿假单胞菌（P. aeruginosa）的抑制效果均较弱，这可能与其极强的黏附与基质生成能力有关。通过共聚焦显微镜（confocal microscopy）评估纳米粒涂层圆盘上的细菌定植情况，进一步验证了上述结果。最后，为排除纳米粒涂层圆盘对真核细胞的细胞毒性，本研究评估了其生物相容性。结果显示，与阴性对照组相比，在Ti-Ag-Cu与Mg-Ag-Cu涂层圆盘共同培养的细胞存活率分别为95.8%与89.4%。综上，本研究证实了Ti-Ag-Cu与Mg-Ag-Cu两种涂层均具备良好的抗黏附特性，同时可有效抑制生物膜形成，凸显了本次测试的多元素纳米粒家族作为对抗细菌黏附至生物医学植入物表面的新型策略的安全性与应用前景。