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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/221097
Development of a Neurovascular Microfluidic Model with an Endothelial Barrier-Integrity Sensor for Pharmaceutical Innovation in Neurodegenerative Diseases
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[eng] Neurodegenerative diseases represent a significant health challenge, as no cure is currently available. The unique anatomy of the blood-brain barrier, which limits drug delivery to the brain, as well as the lack of predictive pre-clinical models, contribute to delays in the drug discovery process.
This research presents the development of two distinct 3D models aimed at advancing pharmaceutical innovation for neurodegenerative diseases. We designed a blood-brain barrier-on-a-chip device that incorporates trans-endothelial electrical resistance electrodes for real-time assessment of barrier integrity. The 3D microfluidic design involves the co-culture of brain endothelial cells, pericytes, and astrocytes, before being fully characterized to verify the proper development of the blood-brain barrier. The developed platform was then utilized to evaluate the permeability and toxicity of novel nanotherapeutic agents for neurodegenerative diseases. Furthermore, a more advanced in vitro model for drug discovery of neurodegenerative diseases was assembled. This model incorporated human induced-neurons along with other cell types to create a neurovascular-unit in vitro. Specifically, we co-cultured human induced neurons with oligodendrocytes, astrocytes, pericytes, and endothelial cells within a microfluidic device. Finally, we monitored the release of neurofilament light, a potential biomarker of neuronal degeneration, in response to exposure to two different neurotoxic agents. Quantifying neurofilament light release enables assessment of neurodegenerative progression and evaluation of potential therapeutic interventions to mitigate disease advancement.
The blood-brain barrier-on-a-chip and neurovascular-unit-on-a-chip models represent a versatile and scalable platform that offers a cost-effective, human-relevant alternative to traditional animal models. These platforms facilitate drug screening and accelerate the discovery of treatments for neurodegenerative diseases.
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PALMA FLOREZ, Sujey. Development of a Neurovascular Microfluidic Model with an Endothelial Barrier-Integrity Sensor for Pharmaceutical Innovation in Neurodegenerative Diseases. [consulta: 28 de novembre de 2025]. [Disponible a: https://hdl.handle.net/2445/221097]