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

Wang, Ke, Sun, Chao, Dumčius, Povilas, Zhang, Hongxin, Liao, Hanlin, Wu, Zhenlin, Tian, Liangfei, Peng, Wang, Fu, Yongqing, Wei, Jun, Cai, Meng, Zhong, Yi, Li, Xiaoyu, Yang, Xin ORCID: https://orcid.org/0000-0002-8429-7598 and Cui, Min 2023. Open source board based acoustofluidic transwells for reversible disruption of the blood–brain barrier for therapeutic delivery. Biomaterials Research 27 (1) , 69. 10.1186/s40824-023-00406-6

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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:

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Engineering
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	BioMed Central
Date of First Compliant Deposit:	17 July 2023
Date of Acceptance:	17 June 2023
Last Modified:	18 Jul 2023 22:50
URI:	https://orca.cardiff.ac.uk/id/eprint/161067

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