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Porous optically transparent cellulose acetate scaffolds for biomimetic blood-brain barrier in vitro models

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journal contribution
posted on 13.09.2021, 13:20 by Attilio Marino, Micol Baronio, Umberto Buratti, Elisa MeleElisa Mele, Gianni Ciofani
In vitro blood-brain barrier (BBB) models represent an efficient platform to conduct high-throughput quantitative investigations on BBB crossing ability of different drugs. Such models provide a closed system where different fundamental variables can be efficaciously tuned and monitored, and issues related to scarce accessibility of animal brains and ethics can be addressed. In this work, we propose the fabrication of cellulose acetate (CA) porous bio-scaffolds by exploiting both vapor-induced phase separation (VIPS) and electrospinning methods. Parameters of fabrication have been tuned in order to obtain porous and transparent scaffolds suitable for optical/confocal microscopy, where endothelial cell monolayers are allowed to growth thus obtaining biomimetic BBB in vitro models. Concerning VIPS-based approach, CA membranes fabricated using 25% H2O + 75% EtOH as non-solvent showed submicrometer-scale porosity and an optical transmittance comparable to that one of commercially available poly(ethylene terephthalate) membranes. CA membranes fabricated via VIPS have been exploited for obtaining multicellular BBB models through the double seeding of endothelial cells and astrocytes on the two surfaces of the membrane. Electrospun CA substrates, instead, were characterized by micrometer-sized pores, and were unsuitable for double seeding approach and long term studies. However, the potential exploitation of the electrospun CA substrates for modeling blood-brain-tumor barrier and studying cell invasiveness has been speculated. The features of the obtained models have been critically compared and discussed for future applications.

Funding

European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Program (grant agreement N◦ 709613, SLaMM)

History

School

  • Aeronautical, Automotive, Chemical and Materials Engineering

Department

  • Materials

Published in

Frontiers in Bioengineering and Biotechnology

Volume

9

Publisher

FRONTIERS MEDIA SA

Version

VoR (Version of Record)

Rights holder

© The authors

Publisher statement

This is an Open Access Article. It is published by Frontiers Media under the Creative Commons Attribution 4.0 Unported Licence (CC BY). Full details of this licence are available at: http://creativecommons.org/licenses/by/4.0/

Acceptance date

20/01/2021

Publication date

2021-02-10

Copyright date

2021

ISSN

2296-4185

eISSN

2296-4185

Language

en

Depositor

Dr Elisa Mele. Deposit date: 7 September 2021

Article number

630063