Institute of Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, London,
Eur Cell Mater. 2018 Oct 2;36:142-155. doi: 10.22203/eCM.v036a11.
Many studies report the adverse responses to metal-on-metal (MoM) hip prostheses, with tissues surrounding failed MoM hip prostheses revealing abundant tissue necrosis and fibrosis. These local effects appear to be initiated by metal ions released from the prosthesis causing the secretion of inflammatory mediators. However, little is known about the effect of the metal ions on tissue remodelling and pseudotumor formation, which are also associated with the failure of MoM hip prostheses. The peri-prosthetic soft tissue masses can lead to pain, swelling, limited range of joint movement and extensive tissue lesion. To elucidate this cellular response, a multidisciplinary approach using both two- and three-dimensional (2D and 3D) in vitro culture systems was employed to study the effects of Co2+ and Cr3+ on human fibroblast activation and mechanobiology. Co2+ induced a fibrotic response, characterised by cytoskeletal remodelling and enhanced collagen matrix contraction. This was associated with increased cell stiffness and contractile forces as measured by atomic force microscopy and traction force microscopy, respectively. These effects were triggered by the generation of reactive oxygen species (ROS). Moreover, this fibrotic response was enhanced in the presence of macrophages, which increased the prevalence of a-smooth muscle actin (a-SMA)-positive fibroblasts and collagen synthesis. Cr3+ did not show any significant effect on fibroblast activation. Co2+ promoted matrix remodelling by fibroblasts that was further enhanced by macrophage signalling. Use of alternative implant materials or manipulation of this fibrotic response could provide an opportunity for enhancing the success of prostheses utilising CoCr alloys.
许多研究报告了金属对金属（MoM）髋关节假体的不良反应，在失败的 MoM 髋关节假体周围的组织中发现大量组织坏死和纤维化。这些局部效应似乎是由假体释放的金属离子引发的，导致炎症介质的分泌。然而，对于金属离子对组织重塑和假瘤形成的影响知之甚少，这些也与 MoM 髋关节假体的失效有关。假体周围软组织肿块可导致疼痛、肿胀、关节活动范围受限和广泛的组织损伤。为了阐明这种细胞反应，采用了一种多学科方法，使用二维（2D）和三维（3D）体外培养系统来研究 Co2+和 Cr3+对人成纤维细胞激活和力学生物学的影响。Co2+诱导了一种纤维化反应，其特征是细胞骨架重塑和增强的胶原基质收缩。这与原子力显微镜和牵引力显微镜分别测量的细胞硬度和收缩力的增加有关。这些效应是由活性氧（ROS）的产生引发的。此外，在巨噬细胞存在的情况下，这种纤维化反应得到增强，增加了 a-平滑肌肌动蛋白（a-SMA）阳性成纤维细胞的发生率和胶原合成。Cr3+对成纤维细胞的激活没有显示出任何显著影响。Co2+通过成纤维细胞促进基质重塑，巨噬细胞信号进一步增强了这种重塑。使用替代植入材料或操纵这种纤维化反应可能为利用 CoCr 合金增强假体的成功提供机会。
