TY - JOUR
T1 - Open source board based acoustofluidic transwells for reversible disruption of the blood–brain barrier for therapeutic delivery
AU - Wang, Ke
AU - Sun, Chao
AU - Dumčius, Povilas
AU - Zhang, Hongxin
AU - Liao, Hanlin
AU - Wu, Zhenlin
AU - Tian, Liangfei
AU - Peng, Wang
AU - Fu, Yongqing
AU - Wei, Jun
AU - Cai, Meng
AU - Zhong, Yi
AU - Li, Xiaoyu
AU - Yang, Xin
AU - Cui, Min
N1 - Funding information: The authors are grateful for the financial support provided by the National Program on Key Research Project of China (SQ2022YFD1800030), the National Natural Sciences Foundation of China (Grant No. 31872455) (M.C), as well as the UK Engineering and Physical Sciences Research Council (EPSRC) under grant EP/P018998/1, and International Exchange Grant (IEC/NSFC/201078) (Y.F) through Royal Society UK and the NSFC.
PY - 2023/7/15
Y1 - 2023/7/15
N2 - 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:
AB - 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:
KW - Human brain microvascular endothelial cells
KW - Blood–brain barrier
KW - Transendothelial electrical resistance
KW - Acoustofluidic transwell
KW - Surface acoustic wave
UR - http://www.scopus.com/inward/record.url?scp=85165259848&partnerID=8YFLogxK
U2 - 10.1186/s40824-023-00406-6
DO - 10.1186/s40824-023-00406-6
M3 - Article
SN - 2055-7124
VL - 27
SP - 1
EP - 16
JO - Biomaterials Research
JF - Biomaterials Research
IS - 1
M1 - 69
ER -