Bio-Orthogonal Engineering of Neural Stem Cells with Membrane-Bound Microsatellites for Enhanced Brain Repair.

IF 26.8 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Advanced Materials Pub Date : 2025-09-08 DOI:10.1002/adma.202511104

Liyang Yu,Dezheng Li,Yuyang Jiao,Shenghan Feng,Yang Liu,Jiawen Chen,Jie Su,Yuanhua Sang,Meixia Ren,Hong Liu,Jichuan Qiu

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Abstract

Regulating the differentiation of implanted stem cells into neurons is crucial for stem cell therapy of traumatic brain injury (TBI). However, due to the migratory nature of implanted stem cells, precise and targeted regulation of their fate remains challenging. Here, neural stem cells (NSCs) are bio-orthogonally engineered with hyaluronic acid methacryloyl (HAMA) microsatellites capable of sustained release of differentiation modulators for targeted regulation of their neuronal differentiation and advanced TBI repair. By employing bio-orthogonal covalent reactions and optimizing the microsatellite size, HAMA microsatellites can stay on membranes for over 10 days owing to the minimal detachment or endocytosis. These microsatellites can thus migrate together with engineered NSCs and release modulators around the cells, actively inducing 45.1% of NSCs to differentiate into neurons compared to only 18.8% for normal NSCs. These microsatellite-engineered stem cells improve brain tissue repair and enhance behavioral recovery in TBI rats after implantation. This strategy holds promise for the advanced treatment of TBI and other neurodegenerative diseases.

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膜结合微卫星神经干细胞增强脑修复的生物正交工程。

调控移植干细胞向神经元的分化是创伤性脑损伤（TBI）干细胞治疗的关键。然而，由于移植干细胞的迁移特性，精确和有针对性地调节其命运仍然具有挑战性。在这里，神经干细胞（NSCs）是用透明质酸甲基丙烯酰（HAMA）微卫星进行生物正极工程的，这些微卫星能够持续释放分化调节剂，以靶向调节其神经元分化和高级创伤性脑损伤修复。通过生物正交共价反应和优化微卫星尺寸，HAMA微卫星可以在膜上停留10天以上，因为它的脱落或内吞作用最小。因此，这些微卫星可以与工程NSCs一起迁移，并在细胞周围释放调节剂，积极诱导45.1%的NSCs分化为神经元，而正常NSCs仅为18.8%。这些微卫星工程干细胞可改善TBI大鼠植入后的脑组织修复和增强行为恢复。这一策略为TBI和其他神经退行性疾病的高级治疗带来了希望。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Advanced Materials 工程技术-材料科学：综合

CiteScore

43.00

自引率

4.10%

发文量

2182

审稿时长

2 months

期刊介绍： Advanced Materials, one of the world's most prestigious journals and the foundation of the Advanced portfolio, is the home of choice for best-in-class materials science for more than 30 years. Following this fast-growing and interdisciplinary field, we are considering and publishing the most important discoveries on any and all materials from materials scientists, chemists, physicists, engineers as well as health and life scientists and bringing you the latest results and trends in modern materials-related research every week.