In vitro microfluidic modelling of the human blood-brain-barrier microvasculature and testing of nanocarrier transport


https://doi.org/10.4081/bse.105
Vol. 1 No. 1 (2020)
Published: 12 February 2020
Human blood-brain-barrier, in vitro testing platform, microfluidic device, self-organized microvasculature, polymer nanoparticles
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Authors

  • Marco Campisi Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy.
  • Sharon W. L. Lee Singapore-MIT Alliance for Research and Technology; Singapore Immunology Network, A*STAR, Singapore.
  • Tatsuya Osaki Institute of Industrial Science, The University of Tokyo, Japan; Department of Biological and Mechanical Engineering, MIT, Cambridge, MA, United States.
  • Luca Possenti Department of Materials and Chemical Engineering, Politecnico di Milano, Milan, Italy.
  • Clara Mattu Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy.
  • Giulia Adriani
  • Valeria Chiono Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy.
  • Roger D. Kamm Department of Biological and Mechanical Engineering, MIT, Cambridge, MA, United States.

The blood-brain barrier (BBB) protects the brain from pathogens but also hinders drug delivery to the central nervous system. Most of the BBB models developed up to date failed to reproduce the human anatomical complexity of brain barriers, contributing to less predictive experimental platforms and poor patient outcomes. To overcome those limitations, the development of reliable in vitro models represents a crucial step towards more effective therapies. This contribution was focused on the development of an in vitro microfluidic model of the BBB able to replicate the human neurovascular organization. The microfluidic model included human induced pluripotent stem cell-derived endothelial cells, brain pericytes, and astrocytes as self-assembled microvascular networks in a 3-dimensional fibrin gel. As previously demonstrated, the BBB model exhibited perfusable and selective microvasculature, with permeability lower than conventional in vitro models and comparable with in vivo rat brain. Permeability of polystyrene nanoparticles (NPs) and synthesized polyurethane NP was measured across the BBB model as compared to conventional Transwell assays. This physiologically relevant BBB model offers an innovative and valuable platform to preclinically predict transport efficacy of drugs and carriers.


Campisi, M., Lee, S. W. L., Osaki, T., Possenti, L., Mattu, C., Adriani, G., Chiono, V., & Kamm, R. D. (2020). In vitro microfluidic modelling of the human blood-brain-barrier microvasculature and testing of nanocarrier transport. Biomedical Science and Engineering, 1(1). https://doi.org/10.4081/bse.105

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