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

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*

*Corresponding author for this work

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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. Graphical Abstract:
Original languageEnglish
Article number69
Pages (from-to)1-16
Number of pages16
JournalBiomaterials Research
Volume27
Issue number1
DOIs
Publication statusPublished - 15 Jul 2023

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