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用于长期脑成像的脑脊液亲和性和生物相容性增强的软颅骨视窗

Cerebrospinal Fluid-philic and Biocompatibility-Enhanced Soft Cranial Window for Long-Term Brain Imaging.

作者信息

Kim Jong Uk, Park Hyejin, Ok Jehyung, Lee Juheon, Jung Woojin, Kim Jiwon, Kim Jaehyun, Kim Suhyeon, Kim Yong Ho, Suh Minah, Kim Tae-Il

机构信息

School of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea.

IMNEWRUN Inc., N Center Bldg. A 5F, Suwon 16419, Republic of Korea.

出版信息

ACS Appl Mater Interfaces. 2022 Apr 6;14(13):15035-15046. doi: 10.1021/acsami.2c01929. Epub 2022 Mar 28.

DOI:10.1021/acsami.2c01929
PMID:35344336
Abstract

Soft, transparent poly(dimethyl siloxane) (PDMS)-based cranial windows in animal models have created many opportunities to investigate brain functions with multiple imaging modalities. However, due to the hydrophobic nature of PDMS, the wettability by cerebrospinal fluid (CSF) is poor, which may cause air bubble trapping beneath the window during implantation surgery, and favorable heterogeneous bubble nucleation at the interface between hydrophobic PDMS and CSF. This may result in excessive growth of the entrapped bubble under the soft cranial window. Herein, to yield biocompatibility-enhanced, trapped bubble-minimized, and soft cranial windows, this report introduces a CSF-philic PDMS window coated with hydroxyl-enriched poly(vinyl alcohol) (PVA) for long-term imaging. The PVA-coated PDMS (PVA/PDMS) film exhibits a low contact angle θ (33.7 ± 1.9°) with artificial CSF solution and maintains sustained CSF-philicity. The presence of the PVA layer achieves air bubble-free implantation of the soft cranial window, as well as induces the formation of a thin wetting film that shows anti-biofouling performance through abundant water molecules on the surface, leading to long-term optical clarity. studies on the mice cortex verify that the soft and CSF-philic features of the PVA/PDMS film provide minimal damage to neuronal tissues and attenuate immune response. These advantages of the PVA/PDMS window are strongly correlated with the enhancement of cortical hemodynamic changes and the local field potential recorded through the PVA/PDMS film, respectively. This collection of results demonstrates the potential for future microfluidic platforms for minimally invasive CSF extraction utilizing a CSF-philic fluidic passage.

摘要

在动物模型中,基于柔软、透明的聚二甲基硅氧烷(PDMS)的颅骨视窗为利用多种成像方式研究脑功能创造了许多机会。然而,由于PDMS的疏水性,其对脑脊液(CSF)的润湿性较差,这可能会在植入手术期间导致视窗下方截留气泡,并在疏水性PDMS与CSF的界面处产生有利的异质气泡成核。这可能会导致柔软颅骨视窗下截留气泡过度生长。在此,为了获得生物相容性增强、截留气泡最小化的柔软颅骨视窗,本报告介绍了一种涂覆有富含羟基的聚乙烯醇(PVA)的亲CSF的PDMS视窗,用于长期成像。涂覆PVA的PDMS(PVA/PDMS)膜与人工脑脊液溶液的接触角θ较低(33.7±1.9°),并保持持续的亲CSF性。PVA层的存在实现了柔软颅骨视窗的无气泡植入,并诱导形成一层薄的润湿膜,该膜通过表面丰富的水分子表现出抗生物污损性能,从而实现长期光学清晰度。对小鼠皮层的研究证实,PVA/PDMS膜的柔软和亲CSF特性对神经元组织的损伤最小,并减弱免疫反应。PVA/PDMS视窗的这些优点分别与通过PVA/PDMS膜记录的皮层血流动力学变化增强和局部场电位密切相关。这一系列结果证明了未来利用亲CSF流体通道进行微创CSF提取的微流控平台的潜力。

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