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Development of an in vitro microfluidic platform to mimic the blood-brain barrier

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Treballs Finals de Grau d'Enginyeria Biomèdica. Facultat de Medicina i Ciències de la Salut. Universitat de Barcelona. Curs: 2022-2023. Directora: Anna Lagunas, Tutor: Manel Puig.

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There are very few models able to simulate with precision the complex structure of the blood-brain
barrier (BBB): our body’s most restrictive barrier which, while protecting our brain from pathogens,
toxins, inflammation, injury and disease, is also the main obstacle for the delivery of drugs to the
brain.
This paper examines all the aspects that have to be taken into account to properly develop, from
scratch, an in vitro microfluidic platform to mimic the human BBB.
The thesis details every step of the fabrication of the device, provides an economic and technical
analysis of its feasibility, and considers the ethical and legal aspects of its implementation to the
market.
Following a thorough analysis of the different existing models of the BBB and their benefits, this
work develops a design incorporating a tri-culture of human astrocytes, pericytes and endothelial
cells ensembled in a 3D environment of hydrogel within a structure of PDMS .
The resulting BBB-on-a-chip (BBB-oC) is an accurate, reproducible, animal-free and cheaper
alternative to in vivo models for mimicking the function and structure of the BBB. Evaluation
techniques carried out in this project showed a suitable environment for the cells inside the chip,
confirming their correct morphology and viability up to the 7th day. Permeability assays revealed
that the barrier is size restrictive, thus allowing smaller molecules to pass through faster than bigger
molecules.
To provide a clinical application to the model, permeability performance tests were conducted on
two different nanotherapeutic systems which target the inhibition of Aβ fibrillation as a possible
treatment for Alzheimer’s disease.

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Treballs Finals de Grau (TFG) - Enginyeria Biomèdica

# metadata.dc.title[].value
Development of an in vitro microfluidic platform to mimic the blood-brain barrier