Abstract

Peripheral Nerve-on-a-Chip: Quantifying Myelination and Demyelination

Michael Moore, Associate Professor of Biomedical Engineering; Co-founder and CSO, AxoSim Technologies, Tulane University

Development of microphysiological models of the peripheral nervous system have lagged that of other organ systems. This is perhaps partially because peripheral nerve disorders are rarely life-threatening, though they are frequently severely debilitating. The most effective organ-on-a-chip models are those that reflect relevant anatomical and physiological features, enabling comparisons with animal studies or clinical outcomes. In our model of rat myelinated peripheral nerve, we show that we can quantify key measurements using histology and nerve conduction, exactly the main quantitative endpoints used in preclinical or clinical studies to assess peripheral nerve degeneration. In particular, we show that nerve conduction velocity correlates with myelin formation, as measured by % myelinated axons and g-ratio. In like manner, induced demyelination leads to structural degeneration and functional deficits that may also be quantified using histology and nerve conduction. This model is unique in its ability to capture these specific metrics of peripheral nerve health. Ongoing challenges and implications for modeling demyelinating disorders will also be discussed.