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Transient opening of an organ-on-a-chip Blood-Brain-Barrier model using ultrasound and monodisperse microbubbles

Persijn van Meerten, P.A.M. van (2021) Transient opening of an organ-on-a-chip Blood-Brain-Barrier model using ultrasound and monodisperse microbubbles.

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Abstract:Treating neurological diseases remain a big challenge for clinicians. The main obstacle in treating these diseases is the Blood-brain-barrier (BBB). The BBB is a very tight barrier consisting of astrocytes, pericytes and endothelial cells connected by tight junctions. Due to the tightness of the BBB, it is difficult to deliver medicine through the BBB. Current treatment options lack specificity or are invasive and not repeatable. However, numerous studies have shown a new technique in temporarily opening the BBB using a combination of ultrasound (US) and gas-filled microbubbles. The microbubbles will oscillate due to the acoustic pressure, which will result in shear stress on the cell layer, causing the BBB to open temporarily. Although the efficacy of the technique is well established, the mechanisms and the safety of the technique are still unclear. Thus, in this study, the technique was applied on a BBB-on-a-chip model, so ultra-high-speed imaging could be performed to capture the microbubble oscillations which could be correlated to the effect it had on the cell layer. For this study, a setup was created in which the chip received US while simultaneously microbubble oscillations could be captured. Furthermore, a live/dead assay was performed to test the viability of the technique, an actin staining was done to see if the cell structures would change due to the technique and a permeability assay was performed. However, the results were disappointing and no decisive conclusions could be drawn from the experiments. Numerous issues and inconsistencies in using the setup need to be resolved first. Furthermore, the cell line that was used is known to have difficulties forming functional tight junctions. A co-culture with astrocytes or the usage of another cell line could solve this problem. In conclusion, no correlation can be made between the microbubble oscillations and its induced bio-effect yet, but the created setup shows promise in giving more insight into the mechanisms behind microbubble-assisted BBB disruption.
Item Type:Essay (Master)
Faculty:TNW: Science and Technology
Programme:Biomedical Engineering MSc (66226)
Link to this item:https://purl.utwente.nl/essays/93172
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