Stochastic Nanoroughness Inhibits and Reverses Glial Scarring In Vitro and In Vivo via a Mechanobiology Paradigm Involving Piezo-1

IF 18.5 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Nils R. Blumenthal, Jeremy C Petravicz, Vincent Breton-Provencher, Ming Hu, Fabian Riemenschneider, Melika Sarem, Mriganka Sur, V. Prasad Shastri
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Abstract

Physical insult to the central nervous system (CNS) such as during electrode insertion leads to reactive astrogliosis which in turn contributes to glial scarring (GS). To date, reducing GS in these settings has focused on pharmacological agents and variations in electrode material composition or implantation procedures, and the role of electrode surface topography has remained unexplored. Since proteoglycans, a major component of GS tissue, possesses very well-defined (nano) topography, a role for stochastic nanoroughness in glial scar formation is theorized. Using an in vitro system, we provide proof of concept that on substrates possessing stochastic nanoroughness corresponding to that of healthy astrocytes, glial scar formation is significantly inhibited, and more importantly, can be even reversed, and it involves signaling via the stretch-activated cation channel Piezo-1. In vivo studies reveal an absence of astrocytes aggregation along the electrode track of chronically implanted electrodes modified with stochastic surface nanoroughness, compared to non-modified electrodes, while signal detection within the superior colliculus remains unaffected. These findings shedlight on the crucial role of stochastic biophysical cues in modulating GS formation; and offer a promising non-chemical approach for engineering neural biomaterials interface for the CNS.

Abstract Image

随机纳米粗糙度通过涉及 Piezo-1 的机械生物学范式抑制和逆转体外和体内神经胶质瘢痕形成
中枢神经系统(CNS)受到的物理损伤(如电极插入时)会导致反应性星形胶质细胞增生,进而造成胶质瘢痕(GS)。迄今为止,在这些情况下减少神经胶质瘢痕的方法主要集中在药理药剂和电极材料成分或植入程序的变化上,而电极表面形貌的作用仍未得到研究。由于 GS 组织的主要成分蛋白多糖具有非常明确的(纳米)形貌,因此理论上认为随机纳米粗糙度在神经胶质瘢痕形成中发挥作用。利用体外系统,我们提供了概念证明,在具有与健康星形胶质细胞相应的随机纳米粗糙度的基质上,胶质瘢痕的形成受到显著抑制,更重要的是,甚至可以逆转,这涉及到通过拉伸激活阳离子通道 Piezo-1 发出信号。体内研究显示,与未修改的电极相比,经过随机表面纳米粗糙度修饰的长期植入电极的电极轨迹上没有星形胶质细胞聚集,而上丘内的信号检测不受影响。这些发现揭示了随机生物物理线索在调节 GS 形成中的关键作用,并为中枢神经系统的神经生物材料界面工程提供了一种前景广阔的非化学方法。
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来源期刊
Advanced Functional Materials
Advanced Functional Materials 工程技术-材料科学:综合
CiteScore
29.50
自引率
4.20%
发文量
2086
审稿时长
2.1 months
期刊介绍: Firmly established as a top-tier materials science journal, Advanced Functional Materials reports breakthrough research in all aspects of materials science, including nanotechnology, chemistry, physics, and biology every week. Advanced Functional Materials is known for its rapid and fair peer review, quality content, and high impact, making it the first choice of the international materials science community.
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