Kontakis Michael G, Carlsson Elin, Palo-Nieto Carlos, Hailer Nils P
OrthoLab, The Rudbeck Laboratory, Department of Surgical Sciences/Orthopedics, Uppsala University, 75185 Uppsala, Sweden.
Exp Ther Med. 2025 Jan 20;29(3):51. doi: 10.3892/etm.2025.12801. eCollection 2025 Mar.
Silver (Ag) possesses potent antimicrobial properties and is used as a coating for medical devices. The impact of silver ions released from orthopedic implants on the differentiation and osteoid formation of different osteogenic cells has yet to be systematically studied. In the present study, human mesenchymal stem cells (hMSCs) and primary human osteoblasts (hOBs) were exposed to different static Ag concentrations (0, 0.5, 1.0 or 1.5 ppm) or dynamic Ag concentrations (range 0 to 0.7 ppm) that simulated the temporal release pattern from a Ag-nitrate coating of trabecular titanium (TLSN). Cell morphology was investigated by phase contrast and fluorescence microscopy. The activities of alkaline phosphatase (ALP) and lactate dehydrogenase, osteogenic gene expression (COL1A1, COL1A2 and ALPL), and osteoid deposition were examined for up to 4 weeks. DAPI and carboxyfluorescein diacetate staining revealed changes in the morphology of hOBs treated with ≥0.5 ppm Ag, while osteocalcin-positive cells were observed primarily in the untreated group. Elevated Ag concentrations did not impact the production of ALP by either hMSCs or hOBs. Treatment with 1.5 ppm Ag or TLSN Ag led to a modest reduction in COL1A2 and ALPL levels in hMSCs at 2 weeks but not at 4 weeks nor in hOBs. In hMSC cultures, mineralization decreased at ≥1 ppm Ag, whereas the same concentration range significantly reduced mineralization in hOB cultures. In conclusion, Ag concentrations ranging from 1.0 to 1.5 ppm may interfere with osteogenic differentiation, possibly by altering gene expression, thereby affecting mineralization. Only Ag concentrations up to 0.5 ppm allowed undisturbed osteogenic differentiation and mineralization. These findings pertain to creating Ag coatings of titanium intended for cementless fixation into host bone.
银（Ag）具有强大的抗菌特性，被用作医疗器械的涂层。骨科植入物释放的银离子对不同成骨细胞的分化和类骨质形成的影响尚未得到系统研究。在本研究中，将人间充质干细胞（hMSCs）和原代人成骨细胞（hOBs）暴露于不同的静态银浓度（0、0.5、1.0或1.5 ppm）或动态银浓度（范围为0至0.7 ppm）下，这些浓度模拟了来自小梁钛（TLSN）硝酸银涂层的时间释放模式。通过相差显微镜和荧光显微镜研究细胞形态。检测碱性磷酸酶（ALP）和乳酸脱氢酶的活性、成骨基因表达（COL1A1、COL1A2和ALPL）以及类骨质沉积，持续时间长达4周。DAPI和羧基荧光素二乙酸酯染色显示，用≥0.5 ppm银处理的hOBs形态发生变化，而骨钙素阳性细胞主要在未处理组中观察到。银浓度升高对hMSCs或hOBs产生ALP的量没有影响。用1.5 ppm银或TLSN银处理在2周时导致hMSCs中COL1A2和ALPL水平适度降低，但在4周时未降低，在hOBs中也未降低。在hMSC培养物中，≥1 ppm银时矿化减少，而相同浓度范围在hOB培养物中显著降低矿化。总之，1.0至1.5 ppm的银浓度可能通过改变基因表达干扰成骨分化，从而影响矿化。只有高达0.5 ppm的银浓度才能实现不受干扰的成骨分化和矿化。这些发现与创建用于无水泥固定到宿主骨中的钛银涂层有关。
