Jacobs Aurélie, Renaudin Guillaume, Charbonnel Nicolas, Nedelec Jean-Marie, Forestier Christiane, Descamps Stéphane
Université Clermont Auvergne, Clermont Auvergne INP, CNRS, ICCF, F-63000 Clermont-Ferrand, France.
Université Clermont Auvergne, CNRS, Laboratoire Microorganismes: Genome et Environnement, F-63000 Clermont-Ferrand, France.
Materials (Basel). 2021 May 4;14(9):2393. doi: 10.3390/ma14092393.
Cytotoxicity and antibacterial properties associated with the dopant release of Cu-doped Biphasic Calcium Phosphate (BCP) powders, mainly composed of hydroxyapatite mixed with β-tricalcium phosphate powders, were investigated. Twelve BCP ceramics were synthesized at three different sintering temperatures (600 °C, 900 °C and 1200 °C) and four copper doping rates ( = 0.0, 0.05, 0.10 and 0.20, corresponding to the stoichiometric amount of copper in CaCu(PO)(OH)O). Cytotoxicity assessments of Cu-doped BCP powders, using MTT assay with human-Mesenchymal Stem Cells (h-MSCs), indicated no cytotoxicity and the release of less than 12 ppm of copper into the biological medium. The antibacterial activity of the powders was determined against both Gram-positive (methicillin-sensitive (MS) and methicillin resistant (MR) ) and Gram-negative ( coli and ) bacteria. The Cu-doped biomaterials exhibited a strong antibacterial activity against MSSA, MRSA and , releasing approximatively 2.5 ppm after 24 h, whereas 10 ppm were required to induce an antibacterial effect against . This study also demonstrated that the culture medium used during experiments can directly impact the antibacterial effect observed; only 4 ppm of Cu were effective for killing all the bacteria in a 1:500 diluted TS medium, whereas 20 ppm were necessary to achieve the same result in a rich, non-diluted standard marrow cell culture medium.
研究了掺杂铜的双相磷酸钙（BCP）粉末（主要由羟基磷灰石与β-磷酸三钙粉末混合而成）的掺杂剂释放所相关的细胞毒性和抗菌性能。在三个不同的烧结温度（600℃、900℃和1200℃）以及四个铜掺杂率（=0.0、0.05、0.10和0.20，对应于CaCu(PO)(OH)O中铜的化学计量量）下合成了12种BCP陶瓷。使用人骨髓间充质干细胞（h-MSCs）的MTT法对掺杂铜的BCP粉末进行细胞毒性评估，结果表明无细胞毒性，且向生物培养基中释放的铜低于12 ppm。测定了该粉末对革兰氏阳性菌（甲氧西林敏感菌（MS）和耐甲氧西林菌（MR））和革兰氏阴性菌（大肠杆菌和）的抗菌活性。掺杂铜的生物材料对甲氧西林敏感金黄色葡萄球菌、耐甲氧西林金黄色葡萄球菌和表现出很强的抗菌活性，24小时后释放约2.5 ppm的铜，而对诱导抗菌作用则需要10 ppm。本研究还表明，实验过程中使用的培养基会直接影响观察到的抗菌效果；在1:500稀释的胰酪大豆胨培养基中，仅4 ppm的铜就能有效杀死所有细菌，而在丰富的、未稀释的标准骨髓细胞培养基中则需要20 ppm才能达到相同的效果。
