Rapid Biofabrication of an Advanced Microphysiological System Mimicking Phenotypical Heterogeneity and Drug Resistance in Glioblastoma.

Autor: Pun S; Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, 45221, USA., Prakash A; Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, 45221, USA.; Abbvie, Worcester, Massachusetts, 01605, USA., Demaree D; Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, 45221, USA.; Thermo Fisher Scientific, Waltham, Massachusetts, 02451, USA., Krummel DP; Department of Neurology, University of Cincinnati, Cincinnati, OH, 45219, USA.; Department of Neurosurgery, University of North Carolina, Chapel Hill, NC, 27599, USA., Sciumè G; Institute of Mechanics and Engineering-12 M, University of Bordeaux, Bordeaux, 33607, France., Sengupta S; Department of Neurology, University of Cincinnati, Cincinnati, OH, 45219, USA.; Department of Neurosurgery, University of North Carolina, Chapel Hill, NC, 27599, USA.; Department of Neurology, University of North Carolina, Chapel Hill, NC, 27599-7025, USA.; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, 27599-7295, USA., Barrile R; Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, 45221, USA.; Center for Stem Cells and Organoid Medicine (CuSTOM), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
Jazyk: angličtina
Zdroj: Advanced healthcare materials [Adv Healthc Mater] 2024 Aug 05, pp. e2401876. Date of Electronic Publication: 2024 Aug 05.
DOI: 10.1002/adhm.202401876
Abstrakt: Microphysiological systems (MPSs) reconstitute tissue interfaces and organ functions, presenting a promising alternative to animal models in drug development. However, traditional materials like polydimethylsiloxane (PDMS) often interfere by absorbing hydrophobic molecules, affecting drug testing accuracy. Additive manufacturing, including 3D bioprinting, offers viable solutions. GlioFlow3D, a novel microfluidic platform combining extrusion bioprinting and stereolithography (SLA) is introduced. GlioFlow3D integrates primary human cells and glioblastoma (GBM) lines in hydrogel-based microchannels mimicking vasculature, within an SLA resin framework using cost-effective materials. The study introduces a robust protocol to mitigate SLA resin cytotoxicity. Compared to PDMS, GlioFlow3D demonstrated lower small molecule absorption, which is relevant for accurate testing of small molecules like Temozolomide (TMZ). Computational modeling is used to optimize a pumpless setup simulating interstitial fluid flow dynamics in tissues. Co-culturing GBM with brain endothelial cells in GlioFlow3D showed enhanced CD133 expression and TMZ resistance near vascular interfaces, highlighting spatial drug resistance mechanisms. This PDMS-free platform promises advanced drug testing, improving preclinical research and personalized therapy by elucidating complex GBM drug resistance mechanisms influenced by the tissue microenvironment.
(© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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