Biomimetic microfibers for myelin-enhancer screening and neural regeneration

Remyelination is crucial for the functional restoration of neural circuits, with oligodendrocyte wrapping of axons being the final and essential step. However, its regulatory mechanisms remain unclear, partly due to the lack of effective evaluation systems of oligodendrocyte wrapping. Here, we developed a novel culture platform with aligned microfibers that mimic axonal structure and chemistry to quantify oligodendrocyte wrapping. Compound screening with this system identified that dimemorfan, a sigma-1 receptor agonist, enhances oligodendrocyte wrapping and transcriptomic profiles detected by RNA-seq. In addition, dimemorfan promoted wrapping in human iPSC-derived oligodendrocytes. Our findings provide a new platform for drug discovery for brain regeneration and advance the understanding of remyelination mechanisms.