Manara - Qatar Research Repository
3 files

Micropatterned Neurovascular Interface to Mimic the Blood–Brain Barrier’s Neurophysiology and Micromechanical Function: A BBB-on-CHIP Model

journal contribution
submitted on 2024-04-24, 06:32 and posted on 2024-04-24, 06:33 authored by Ajay Vikram Singh, Vaisali Chandrasekar, Peter Laux, Andreas Luch, Sarada Prasad Dakua, Paolo Zamboni, Amruta Shelar, Yin Yang, Vaibhav Pandit, Veronica Tisato, Donato Gemmati

A hybrid blood–brain barrier (BBB)-on-chip cell culture device is proposed in this study by integrating microcontact printing and perfusion co-culture to facilitate the study of BBB function under high biological fidelity. This is achieved by crosslinking brain extracellular matrix (ECM) proteins to the transwell membrane at the luminal surface and adapting inlet–outlet perfusion on the porous transwell wall. While investigating the anatomical hallmarks of the BBB, tight junction proteins revealed tortuous zonula occludens (ZO-1), and claudin expressions with increased interdigitation in the presence of astrocytes were recorded. Enhanced adherent junctions were also observed. This junctional phenotype reflects in-vivo-like features related to the jamming of cell borders to prevent paracellular transport. Biochemical regulation of BBB function by astrocytes was noted by the transient intracellular calcium effluxes induced into endothelial cells. Geometry-force control of astrocyte–endothelial cell interactions was studied utilizing traction force microscopy (TFM) with fluorescent beads incorporated into a micropatterned polyacrylamide gel (PAG). We observed the directionality and enhanced magnitude in the traction forces in the presence of astrocytes. In the future, we envisage studying transendothelial electrical resistance (TEER) and the effect of chemomechanical stimulations on drug/ligand permeability and transport. The BBB-on-chip model presented in this proposal should serve as an in vitro surrogate to recapitulate the complexities of the native BBB cellular milieus.

Other Information

Published in: Cells
See article on publisher's website:



  • English



Publication Year

  • 2022

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Medical Corporation
  • Hamad Bin Khalifa University
  • College of Science and Engineering - HBKU

Usage metrics

    College of Science and Engineering - HBKU



    Ref. manager