Brain-on-a-chip: An emerging platform for studying the nanotechnology-biology interface for neurodegenerative disorders
Open accessAbstract
Neurological disorders have for a long time been a global challenge dismissed by drug companies, especially due to the low efficiency of most therapeutic compounds to cross the brain capillary wall, that forms the blood-brain barrier (BBB) and reach the brain. This has boosted an incessant search for novel carriers and methodologies to drive these compounds throughout the BBB. However, it remains a challenge to artificially mimic the physiology and function of the human BBB, allowing a reliable, reproducible and throughput screening of these rapidly growing technologies and nanoformulations (NFs). To surpass these challenges, brain-on-a-chip (BoC) - advanced microphysiological platforms that emulate key features of the brain composition and functionality, with the potential to emulate pathophysiological signatures of neurological disorders, are emerging as a microfluidic tool to screen new brain-targeting drugs, investigate neuropathogenesis and reach personalized medicine. In this review, the advance of BoC as a bioengineered screening tool of new brain-targeting drugs and NFs, enabling to decipher the intricate nanotechnology-biology interface is discussed. Firstly, the main challenges to model the brain are outlined, then, examples of BoC platforms to recapitulate the neurodegenerative diseases and screen NFs are summarized, emphasizing the current most promising nanotechnological-based drug delivery strategies and lastly, the integration of high-throughput screening biosensing systems as possible cutting-edge technologies for an end-use perspective is discussed as future perspective.
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Brain-on-a-chip technology, unlike conventional static in vitro models, incorporates endothelial barrier formation, fluid flow, and cell-cell interactions, enabling a more accurate assessment of NPs transport mechanisms and their effects in a realistic model that mimics key features of AD physiology.
“More specifically, brain-on-a-chip technology, unlike conventional static in vitro models, incorporates endothelial barrier formation, fluid flow, and cell–cell interactions, enabling a more accurate assessment of NPs transport mechanisms and their effects in a realistic model that mimics key features of AD physiology [132].”
From Advances in Strategies to Transport Nanoparticles Across the Blood–Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer’s Disease (2026) · cites this paper as [132]
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Experimental — accuracy not yet measuredOrgan-on-a-chip platforms have gathered increased attention due to their capacity to emulate human physiology and homeostasis with enhanced reproducibility while reducing animal use in accordance with the 3Rs principle.
“Recently, organ-on-a-chip platforms have gathered increased attention due to their capacity to emulate human physiology and homeostasis with enhanced reproducibility while reducing animal use in accordance with the 3Rs principle.”
From Advances in Strategies to Transport Nanoparticles Across the Blood–Brain Barrier for Drug Delivery into the Brain for the Treatment of Alzheimer’s Disease (2026) · cites this paper as [132]
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- Authors
- Rodrigues, R. O., Shin, S.-R., & Bañobre-López, M.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Shin, Su-Ryon
- ORCID
- Rodrigues, Raquel O.
- Venue
- Journal of Nanobiotechnology
- Published
- 2024-09-18
- Volume
- 22
- Issue
- 1
- Pages
- 573-573
- ISSN
- 1477-3155 (ISSN-L)
- PMC
- PMC11409741
- OpenAlex
- W4402640156
- Cited by
- 44
- References
- 127
- Citations by year
- 2026: 19 · 2025: 23 · 2024: 2
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Nanobiotechnology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- European Commission (2014‐2020, HORIZON2020, 0624_2IQBIONEURO_6_E, 101032481)
- Interreg (0624_2IQBIONEURO_6_E, 2014-2020)
- HORIZON EUROPE Marie Sklodowska-Curie Actions (No 101032481)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neural Engineering
- Keywords
- brain-on-a-chip, blood-brain barrier, neurodegenerative diseases, nanoformulations, microphysiological systems, high-throughput screening, biosensing, personalized medicine, drug screening
- MeSH terms
- Animals, Blood-Brain Barrier, Brain, Humans, Drug Delivery Systems, Neurodegenerative Diseases, Nanotechnology, Lab-On-A-Chip Devices
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