Tunable hydrogel-based micropillar arrays for myelination studies

Le résumé fourni par la source

Oligodendrocytes enable rapid central nervous system signaling by myelinating axons. Here, to model key biomechanical cues regulating myelination, we developed a tunable hydrogel-based micropillar array system that mimics the three-dimensional architecture and softness of axons. This platform supports the long-term culture of oligodendrocytes and robust formation of multilayered compact myelin by rodent and human oligodendrocytes. Using confocal and transmission electron microscopy, we observed a strong linear correlation between immunostained myelin thickness and the number of myelin wraps, enabling high-content quantification of myelination. Systematic variation of pillar stiffness, diameter and surface chemistry within pathophysiological ranges revealed that both mechanical and geometric properties of axon-like substrates critically regulate oligodendrocyte differentiation and myelin wrapping. Importantly, we demonstrate that pharmacological agents exhibit stiffness-dependent effects on myelination, suggesting that overly rigid in vitro models may yield false-positive drug hits. This platform offers a physiologically relevant, high-throughput assay for dissecting oligodendrocyte biology and discovering remyelinating therapies for diseases such as multiple sclerosis.

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