Biomimetic Microfibers for Myelin-Enhancer Screening and Neural Regeneration.

Remyelination requires the precise wrapping of axons by oligodendrocyte processes, a critical step for restoring neural circuit function. However, a lack of quantitative systems that recapitulate axonal geometry and chemistry has limited mechanistic and pharmacological insights into myelin wrapping. Here, we present a bioengineered microfiber platform that mimics neurite architecture and surface chemistry, enabling high-content quantification of oligodendrocyte wrapping. Through compound screening, we identified dimemorfan, a clinically used sigma-1 receptor agonist, as a potent enhancer of myelin wrapping. Dimemorfan treatment accelerated remyelination and functional recovery in demyelinated mice and promoted myelin wrapping by human induced pluripotent stem cell (iPSC)-derived oligodendrocytes. Moreover, population-level magnetic resonance imaging (MRI) analyses revealed increased white matter volume in dimemorfan-administered individuals. This study establishes a biomimetic materials platform for myelin quantification and regeneration-oriented drug discovery, providing mechanistic and translational insights into sigma-1 receptor-mediated control of myelin wrapping.