Toxicity risk from hip implant CoCrMo particles: The impact of dynamic flow rate on neuronal cells in microfluidic systems

In patients with total hip replacements (THRs), wear products in the form of nanoparticles and ions are released, especially around implant failure. In this study, we use N2a cells, a neuroblastoma cell line, to evaluate the effects of different flow rates on neuronal toxicity amidst exposure to CoCrMo particles. We hypothesized that increasing flow rates would increase N2a cell viability and decrease N2a cell-degradation products (DPs) toxicity. We conducted four 24-hour experiments, each with four flow rate conditions, 0, 50, 100, and 200 μL/min, based on the physiological shear stress of the vessels in the human body, to evaluate cell viability, cell morphology, and cell-DPs interaction. Steps included microfluidic channel preparation, N2a cell culturing, CoCrMo particle acquisition, microfluidic system assembly, and dynamic flow neurotoxicity evaluation, which included video microscopy, AlamarBlue, live/dead imaging, DAPI, and ROS assay. The results suggest that fewer neurotoxic reactions and greater viability at higher flow rates supported our hypothesis, although the full range of viable flow rates is yet to be studied. While cell-particle interaction is complex and dynamic, flow rate did modulate toxicity, viability, morphology, and growth environment. The microfluidic system should continue to be developed to study toxicology aspects of implants by simulating in vivo conditions more accurately.