In biological safety evaluation of medical devices, false-negative results have been observed during skin irritation testing using the reconstructed human epidermis (RhE) model when measuring cell viability as a single marker. Therefore, to improve testing accuracy, this study conducted a comprehensive survey and performance evaluation of cytokines to identify a second marker. In addition to IL-1α, macrophage migration inhibitory factor (MIF) was newly identified as a candidate marker, in the Bio-Plex assay of EpiDerm model exposed to polymer sample extracts. Irritation based on cell viability level was not accurately determined in LabCyte model using silicone spiked with 25% heptanoic acid (HA). By contrast, the irritation potency was accurately assessed in detail by measuring IL-1α or MIF. Further, IL-1α and MIF levels in EpiDerm, LabCyte, and EpiSkin models stimulated with sodium dodecyl sulfate (SDS) were inversely correlated with cell viability, and were detected even at low SDS concentrations without cell toxicity. Additionally, MIF demonstrated greater S/N ratio and dose-dependency at high SDS concentrations in some models compared to IL-1α. These results indicated that MIF might be a useful second marker for improving the sensitivity and accuracy of skin irritation testing with RhE models.

在医疗设备的生物安全性评估中，在测量细胞生存力作为单个标记物时，使用重建的人表皮（RhE）模型在皮肤刺激性测试过程中观察到了假阴性结果。因此，为提高测试准确性，本研究进行了细胞因子的全面调查和性能评估，以识别第二种标记。除了IL-1α，在暴露于聚合物样品提取物的EpiDerm模型的Bio-Plex分析中，巨噬细胞迁移抑制因子（MIF）被新鉴定为候选标记。使用掺有25％庚酸（HA）的有机硅在LabCyte模型中无法准确确定基于细胞活力水平的刺激性。相比之下，通过测量IL-1α或MIF可以准确，准确地评估刺激力。此外，EpiDerm，LabCyte，十二烷基硫酸钠（SDS）刺激的EpiSkin和EpiSkin模型与细胞活力呈负相关，即使在低SDS浓度下也能检测到，而没有细胞毒性。此外，与IL-1α相比，在某些模型中，MIF在高SDS浓度下显示出更高的信噪比和剂量依赖性。这些结果表明，MIF可能是提高RhE模型对皮肤刺激性试验的敏感性和准确性的有用的第二标记。