Single-Cell Resolution Mapping of Osteoarthritis-Associated Chondrocyte Dynamics Using a High-Density CMOS MEA Platform.

Abstract

Fibrosis is a major cause of chronic tissue dysfunction and contributes substantially to morbidity and mortality worldwide. Osteoarthritis (OA), affecting over 590 million people, is a prevalent fibrotic joint disease for which disease-modifying therapies remain lacking, partly because disease progression remains incompletely understood. As human-relevant in vitro models, including organ-on-chip and microphysiological systems, become increasingly important, non-invasive technologies capable of continuous cellular monitoring are urgently needed. Here, we implement high-density complementary metal-oxide-semiconductor (CMOS) multielectrode array (MEA)-based impedance profiling as a label-free platform for longitudinal assessment of OA-relevant chondrocyte remodeling. Human primary chondrocytes cultured on CMOS-MEA chips exhibited impedance increases that correlated with electrode occupancy and extracellular matrix (ECM) deposition. Spatial impedance mapping enabled visualization of injury-response dynamics, while oxidative stress induced progressive impedance decline accompanied by apoptosis, morphological remodeling, and chondrocyte dedifferentiation, evidenced by reduced collagen II and SOX9 expression and increased collagen I expression. In contrast, osteogenic de-differentiation produced increased impedance associated with ECM remodeling and matrix mineralization. Together, these findings support high-density CMOS-MEA impedance profiling as a non-invasive approach for monitoring cellular remodeling and provide a foundation for future integration of spatially resolved impedance sensing into advanced microphysiological systems for OA and other fibrotic diseases.