Hydrogel 3D in vitro tumor models for screening cell aggregation mediated drug response
authors Monteiro, MV; Gaspar, VM; Ferreira, LP; Mano, JF
nationality International
journal BIOMATERIALS SCIENCE
keywords BREAST-CANCER; ANIMAL-MODELS; CULTURE; SPHEROIDS; DISCOVERY; STIFFNESS; MATRIGEL; MATRICES; SYSTEM
abstract Hydrogel-based 3D in vitro models comprising tumor ECM-mimetic biomaterials exhibit superlative potential as preclinical testing platforms for drug discovery and bioperformance screening. However, during hydrogel design and testing stages, the ideal selection between cancer cell laden 3D models or spheroid embedded hydrogel platforms remains to be elucidated. Selecting a disease-mimicking cellular arrangement within ECM hydrogels is paramount for anti-cancer therapeutics performance evaluation and may lead to differential outcomes. To investigate the effects assigned to varying cellular-arrangement, we developed dense 3D spheroid microtumors and cell-laden MG-63 osteosarcoma platforms embedded in GelMA and Matrigel ECM-mimetic scaffolds. These platforms enabled cancer cells/3D microtissues maturation and lorlatinib drug performance screening. Initial 3D spheroids assembly via the liquid overlay technique, resulted in the fabrication of dense cellular aggregates with reproducible size, morphology and necrotic core formation, thus mimicking the native tumor. Upon in vitro maturation, MG-63 spheroids encapsulated in hydrogel scaffolds exhibited significantly higher invasion and drug resistance than their cell laden hydrogel counterparts. Such data reveals inherent physiological and drug response variances among randomly distributed osteosarcoma cells and 3D spheroid-laden hydrogels. Overall, this highlights the importance of evaluating different cellular aggregation states when designing ECM-mimetic hydrogels for in vitro tumor modeling and high-throughput screening of anti-cancer therapeutics.
publisher ROYAL SOC CHEMISTRY
issn 2047-4830
year published 2020
volume 8
issue 7
beginning page 1855
ending page 1864
digital object identifier (doi) 10.1039/c9bm02075f
web of science category Materials Science, Biomaterials
subject category Materials Science
unique article identifier WOS:000528593000004
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journal analysis (jcr 2019):
journal impact factor 6.183
5 year journal impact factor 5.468
category normalized journal impact factor percentile 85.526
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