TY - JOUR
T1 - Development of a device useful to reproducibly produce large quantities of viable and uniform stem cell spheroids with controlled diameters
AU - Decarli, Monize Caiado
AU - de Castro, Mateus Vidigal
AU - Nogueira, Júlia Adami
AU - Nagahara, Mariana Harue T
AU - Westin, Cecília Buzatto
AU - de Oliveira, Alexandre Leite R
AU - da Silva, Jorge Vicente L
AU - Moroni, Lorenzo
AU - Mota, Carlos
AU - Moraes, Ângela Maria
N1 - Copyright © 2022 Elsevier B.V. All rights reserved.
PY - 2022/4
Y1 - 2022/4
N2 - Three-dimensional cellular aggregates can mimic the natural microenvironment of tissues and organs and obtaining them through controlled and reproducible processes is mandatory for scaling up and implementing drug cytotoxicity and efficacy tests, as well as tissue engineering protocols. The purpose of this work was to develop and evaluate the performance of a device with two different geometries fabricated by additive manufacturing. The methodology was based on casting a microwell array insert using a non-adhesive hydrogel to obtain highly regular microcavities to standardize spheroid formation and morphology. Spheroids of dental pulp stem cells, bone marrow stromal cells and embryonic stem cells showing high cell viability and average diameters of around 253, 220, and 500 μm, respectively, were produced using the device with the geometry considered most adequate. The cell aggregates showed sphericity indexes above 0.9 and regular surfaces (solidity index higher than 0.96). Around 1000 spheroids could be produced in a standard six-well plate. Overall, these results show that this method facilitates obtaining a large number of uniform, viable spheroids with pre-specified average diameters and through a low-cost and reproducible process for a myriad of applications.
AB - Three-dimensional cellular aggregates can mimic the natural microenvironment of tissues and organs and obtaining them through controlled and reproducible processes is mandatory for scaling up and implementing drug cytotoxicity and efficacy tests, as well as tissue engineering protocols. The purpose of this work was to develop and evaluate the performance of a device with two different geometries fabricated by additive manufacturing. The methodology was based on casting a microwell array insert using a non-adhesive hydrogel to obtain highly regular microcavities to standardize spheroid formation and morphology. Spheroids of dental pulp stem cells, bone marrow stromal cells and embryonic stem cells showing high cell viability and average diameters of around 253, 220, and 500 μm, respectively, were produced using the device with the geometry considered most adequate. The cell aggregates showed sphericity indexes above 0.9 and regular surfaces (solidity index higher than 0.96). Around 1000 spheroids could be produced in a standard six-well plate. Overall, these results show that this method facilitates obtaining a large number of uniform, viable spheroids with pre-specified average diameters and through a low-cost and reproducible process for a myriad of applications.
KW - 3D cell culture
KW - 3D cell model
KW - CULTURE
KW - Cell spheroid
KW - DESIGN
KW - DRUG
KW - In vitro model
KW - MODELS
KW - MULTICELLULAR SPHEROIDS
KW - Microwell array
KW - NECROSIS
KW - ON-A-CHIP
KW - Stem cells
KW - additive manufacturing
U2 - 10.1016/j.msec.2022.112685
DO - 10.1016/j.msec.2022.112685
M3 - Article
C2 - 35589471
SN - 0928-4931
VL - 135
JO - Biomaterials Advances
JF - Biomaterials Advances
M1 - 112685
ER -