Aligned Electrospun PELA Fibers Promote the Neuronal Orientation and Attenuate Neurotoxicity

Neural regeneration is one of the potential therapeutic approaches for Alzheimer's disease (AD). While aligned electrospun fibers have shown promise in guiding neural regeneration, conventional materials face limitations such as poor hydrophilicity and acidic degradation byproducts. The amphiphilic copolymer poly(lactic- co -glycolic acid)- block -polyethylene glycol (PELA) combines mechanical tunability with enhanced biocompatibility, but its potential as an aligned fibrous membrane for neural regeneration remains unexplored. Here, we fabricated aligned electrospun PELA fibrous membranes (AEF) by modulating the collector rotation speeds. Compared to randomly oriented fibers, AEF exhibited highly ordered fiber alignment, enhanced molecular orientation and crystallinity, improved thermal stability, and increased mechanical anisotropy. When cultured with SH-SY5Y human neuroblastoma cells, AEF effectively directed oriented neural outgrowth and reduced cellular dispersion. In an okadaic acid (OA)-induced neural damage model, AEF significantly attenuated oxidative stress and rescued neuronal proliferation. Moreover, AEF mitigated OA-induced Tau hyperphosphorylation and protein aggregation, while restoring the expression of MAP2 and TUBULIN3. Collectively, these findings demonstrate that aligned electrospun PELA fibers not only provide guidance for neuronal orientation but also exert protective effects against Tau-induced neurotoxicity. This study suggests oriented PELA fibrous membranes as promising candidates for ameliorating neural damage in AD.