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

Article dans une revue avec comité de lecture
Author
ccPUN, Sirjana
ccPRAKASH, Anusha
107363 University of Cincinnati [UC]
DEMAREE, Dalee
107363 University of Cincinnati [UC]
KRUMMEL, Daniel Pomeranz
ccSCIUME, Giuseppe
1002421 Institut de Mécanique et d'Ingénierie de Bordeaux [I2M]
SENGUPTA, Soma
44261 University of North Carolina [Chapel Hill] [UNC]
BARRILE, Riccardo

URI
http://hdl.handle.net/10985/25648
DOI
10.1002/adhm.202401876
Date
2024-08-05
Journal
Advanced Healthcare Materials

Abstract

AbstractMicrophysiological 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.

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