Parallel-Shaped poly(L-lactic acid) electrospun membrane promotes facial nerve injury regeneration by upregulating miR-451a expression.

Facial nerve injury (FNI) causes devastating sequelae, including impaired eyelid closure, dysphagia, and permanent facial asymmetry, leading to long-term functional deficits and profound psychosocial impacts that pose significant rehabilitation challenges. To address this, neural regenerative scaffolds represent a promising therapeutic alternative. This study engineered poly(L-lactic acid) (PLLA) electrospun membranes with parallel topographical cues (Align) and functionalized miR-451a-incorporated scaffolds (miR-451a mimics@PLLA) via electrostatic spinning, aiming to decipher how topographical cues steer neurogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and their crosstalk with microRNA regulation. We demonstrate that parallel topography substantially upregulates neurulation-associated biomarkers (Tuj-1, S100, NeuroD1, Map2, and Nestin) in BMSCs, while miR-451a synergistically enhances this differentiation efficacy. The developed miR-451a mimics@PLLA scaffold effectively promotes BMSC neurogenic commitment and functional nerve regeneration, offering a novel biomimetic strategy to overcome FNI complications. This work pioneers synergistic integration of topological engineering and miRNA delivery for next-generation neural repair scaffolds.