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

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 ef...

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Detalles Bibliográficos
Autores principales: 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, Cui, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10349484/
https://www.ncbi.nlm.nih.gov/pubmed/37452381
http://dx.doi.org/10.1186/s40824-023-00406-6
Descripción
Sumario: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: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40824-023-00406-6.