Open source board based acoustofluidic transwells for reversible disruption of the blood-brain barrier for therapeutic delivery.

IF 11.3 1区医学 Q1 Medicine

Biomaterials Research Pub Date : 2023-07-15 DOI:10.1186/s40824-023-00406-6

Ke Wang, Chao Sun, Povilas Dumčius, Hongxin Zhang, Hanlin Liao, Zhenlin Wu, Liangfei Tian, Wang Peng, Yongqing Fu, Jun Wei, Meng Cai, Yi Zhong, Xiaoyu Li, Xin Yang, Min Cui

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Abstract

Background: Blood-brain barrier (BBB) is a crucial but dynamic structure that functions as a gatekeeper for the central nervous system (CNS). Managing sufficient substances across the BBB is a major challenge, especially in the development of therapeutics for CNS disorders.

Methods: To achieve an efficient, fast and safe strategy for BBB opening, an acoustofluidic transwell (AFT) was developed for reversible disruption of the BBB. The proposed AFT was consisted of a transwell insert where the BBB model was established, and a surface acoustic wave (SAW) transducer realized using open-source electronics based on printed circuit board techniques.

Results: In the AFT device, the SAW produced acousto-mechanical stimulations to the BBB model resulting in decreased transendothelial electrical resistance in a dose dependent manner, indicating the disruption of the BBB. Moreover, SAW stimulation enhanced transendothelial permeability to sodium fluorescein and FITC-dextran with various molecular weight in the AFT device. Further study indicated BBB opening was mainly attributed to the apparent stretching of intercellular spaces. An in vivo study using a zebrafish model demonstrated SAW exposure promoted penetration of sodium fluorescein to the CNS.

Conclusions: In summary, AFT effectively disrupts the BBB under the SAW stimulation, which is promising as a new drug delivery methodology for neurodegenerative diseases.

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开放源代码板为基础的声流体传输管可逆破坏血脑屏障治疗输送。

背景:血脑屏障(BBB)是中枢神经系统(CNS)的看门人，是一个至关重要的动态结构。在血脑屏障中管理足够的物质是一项重大挑战，特别是在中枢神经系统疾病治疗方法的开发中。方法:为了实现高效、快速、安全的血脑屏障打开策略，研制了一种可可逆破坏血脑屏障的声流流体传输井(AFT)。所提出的AFT由建立BBB模型的transwell插入件和基于印刷电路板技术的开源电子器件实现的表面声波(SAW)换能器组成。结果:在AFT装置中，SAW对血脑屏障模型产生声力学刺激，导致经内皮电阻以剂量依赖的方式降低，表明血脑屏障破坏。此外，SAW刺激增强了AFT装置对荧光素钠和不同分子量的fitc -葡聚糖的跨内皮通透性。进一步的研究表明血脑屏障的开放主要是由于细胞间隙的明显拉伸。一项使用斑马鱼模型的体内研究表明，SAW暴露促进了荧光素钠对中枢神经系统的渗透。结论:综上所述，AFT在SAW刺激下有效地破坏血脑屏障，有望成为神经退行性疾病的一种新的给药方法。

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

Biomaterials Research Medicine-Medicine (miscellaneous)

CiteScore

10.20

自引率

3.50%

发文量

审稿时长

30 days

期刊介绍： Biomaterials Research, the official journal of the Korean Society for Biomaterials, is an open-access interdisciplinary publication that focuses on all aspects of biomaterials research. The journal covers a wide range of topics including novel biomaterials, advanced techniques for biomaterial synthesis and fabrication, and their application in biomedical fields. Specific areas of interest include functional biomaterials, drug and gene delivery systems, tissue engineering, nanomedicine, nano/micro-biotechnology, bio-imaging, regenerative medicine, medical devices, 3D printing, and stem cell research. By exploring these research areas, Biomaterials Research aims to provide valuable insights and promote advancements in the biomaterials field.