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Updated: Apr 13, 2026
Preparation of 3D Collagen Gels and Microchannels for the Study of 3D Interactions In Vivo
Published on: May 9, 2016
Collagen I Microfiber Promotes Brain Capillary Network Formation in Three-Dimensional Blood-Brain Barrier
Kimiko Nakayama-Kitamura1, Yukari Shigemoto-Mogami1, Marie Piantino2
1Laboratory of Neuropharmacology, Division of Pharmacology, National Institute of Health Sciences, 3-25-26, Tonomachi, Kawasaki-ku, Kawasaki City 210-9501, Kanagawa, Japan.
Background:
The blood-brain barrier (BBB) strictly regulates the penetration of substances into the brain, which, although important for maintaining brain homeostasis, may delay drug development because of the difficulties in predicting pharmacokinetics/pharmacodynamics (PKPD), toxicokinetics/toxicodynamics (TKTD), toxicity, safety, and efficacy in the central nervous system (CNS). Moreover, BBB functional proteins show species differences; therefore, humanized in vitro BBB models are urgently needed to improve the predictability of preclinical studies. Recently, international trends in the 3Rs in animal experiments and the approval of the FDA Modernization Act 2.0 have accelerated the application of microphysiological systems (MPSs) in preclinical studies, and in vitro BBB models have become synonymous with BBB-MPSs. Recently, we developed an industrialized humanized BBB-MPS, BBB-NET. In our previous report, we reproduced transferrin receptor (TfR)-mediated transcytosis with high efficiency and robustness, using hydrogels including fibrin and collagen I microfibers (CMFs).
Methods:
We investigated how adding CMFs to the fibrin gel benefits BBB-NETs.
Results:
We showed that CMFs accelerate capillary network formation and maturation by promoting astrocyte (AC) survival, and clarified that integrin β1 is involved in the mechanism of CMFs.
Conclusions:
Our data suggest that the quality control (QC) of CMFs is important for ensuring the stable production of BBB-NETs.
