Abstract
The high-throughput, label-free Corning Epic assay has applications in drug discovery, pharmacogenomics, cell receptor signaling, cell migration, and viral titration. The utility of Epic technology for biocompatibility testing has not been well established. In manufacturing of medical devices, in vitro and in vivo biocompatibility assessments are mandatory, according to ISO 10993. The new medical device regulation MDR 745/2017 specifies that ex vivo assays that can closely recapitulate in vivo scenarios are needed to better evaluate biomedical devices. We propose herein that Epic technology—which enables detection of variations in cell mass distribution—is suitable for biocompatibility screening of compounds. In this study, we challenged primary human osteoblasts, endothelial cells, and neurons derived from induced pluripotent stem cells with specific concentrations of methyl methacrylate (MMA). Polymeric MMA has long been applied in cranioplasty, where it makes contact with multiple cell types. Application of Epic technology yielded real-time cytotoxicity profiles for all considered cell types. The results were compared with those from microscopic observation of the same culture plate used in the Epic analyses. The Epic assay should be further examined for its utility for cell biology, genomics, and proteomics companion assays. Our results suggest that Epic technology can be applied to biocompatibility evaluation of human cells in medical device development.
Highlights
Medical devices in development must be evaluated for biocompatibility in accordance with ISO 10993 [1]
Cells exposed to sodium dodecyl sulfate (SDS)—the positive cytotoxic control—exhibited a progressive reduction in response, relative to the basal level for each cell type (−0.2 ± 2.1 pm and 1.7 ± 1.1 pm for osteoblasts and human umbilical vein endothelial cells (HUVECs), respectively; baseline data not shown)
Hyperbolic 1-phase decay curve with a plateau of −685.3 ± 13.5 pm and −998.7 ± 37.2 pm for osteoblasts and HUVECs, respectively. This curve was associated with a span of 579.4 ± 36.9 pm and 376.1 ± 90.1 pm for osteoblasts and HUVECs, respectively (Fig 2A and 2E), suggesting a greater sensitivity of osteoblasts to methyl methacrylate (MMA)
Summary
Medical devices in development must be evaluated for biocompatibility in accordance with ISO 10993 [1] This includes cytotoxicity and in vivo tests, such as irritation, intracutaneous reactivity, and sensitization, for all classes of medical devices [2,3,4]. ISO 10993–5 mandates use of the methylthiazolyl tetrazolium (MTT) assay with 3T3 or L929 murine cells cultured with extracts derived from test samples, obtained according to ISO 10993–12 [5]. The MTT assay must be undertaken with separate cell culture plates for each time point [7,8,9]. This assay is associated with a long incubation time (up to 4 hours) prior to colorimetric detection. The initial cell response cannot be observed with this method [6]
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