TY - JOUR
T1 - A Miniaturized EHT Platform for Accurate Measurements of Tissue Contractile Properties
AU - Dostanic, M.
AU - Stein, Jeroen
AU - Windt, Laura
AU - van Meer, Berend
AU - Bellin, Milena
AU - Orlova, Valeria
AU - Mastrangeli, M.
AU - Mummery, Christine
AU - Sarro, P.M.
PY - 2020/7/30
Y1 - 2020/7/30
N2 - We present a wafer-scale fabricated, PDMS-based platform for culturing miniaturized engineered heart tissues (EHTs) which allows highly accurate measurements of the contractile properties of these tissues. The design of the platform is an anisometrically downscaled version of the Heart-Dyno system, consisting of two elastic micropillars inside an elliptic microwell with volume ranging from 3 down to 1μL which supports EHT formation. Size downscaling facilitates fabrication of the platform and makes it compatible with accurate and highly reproducible batch wafer-scale processing; furthermore, downscaling reduces the cost of cell cultures and increases assay throughput. After fabrication, the devices were characterized by nanoindentation to assess the mechanical properties of the pillars and transferred to 96-well plates for cell seeding. Regardless the size of the platform, cell seeding resulted in successful formation of EHTs and all tissues were functionally active (i.e. showed cyclic contractions). The precise characterization of the stiffness of the micropillars enabled accurate measurements of the contractile forces exerted by the cardiac tissues through optical tracking of micropillar displacement. The miniature EHT platforms described in this paper represent a proper microenvironment for culturing and studying EHTs.
AB - We present a wafer-scale fabricated, PDMS-based platform for culturing miniaturized engineered heart tissues (EHTs) which allows highly accurate measurements of the contractile properties of these tissues. The design of the platform is an anisometrically downscaled version of the Heart-Dyno system, consisting of two elastic micropillars inside an elliptic microwell with volume ranging from 3 down to 1μL which supports EHT formation. Size downscaling facilitates fabrication of the platform and makes it compatible with accurate and highly reproducible batch wafer-scale processing; furthermore, downscaling reduces the cost of cell cultures and increases assay throughput. After fabrication, the devices were characterized by nanoindentation to assess the mechanical properties of the pillars and transferred to 96-well plates for cell seeding. Regardless the size of the platform, cell seeding resulted in successful formation of EHTs and all tissues were functionally active (i.e. showed cyclic contractions). The precise characterization of the stiffness of the micropillars enabled accurate measurements of the contractile forces exerted by the cardiac tissues through optical tracking of micropillar displacement. The miniature EHT platforms described in this paper represent a proper microenvironment for culturing and studying EHTs.
KW - Engineered heart tissue
KW - microfabrication
KW - nanoindentation
KW - organs-on-chip
KW - pluripotent stem cells
UR - http://www.scopus.com/inward/record.url?scp=85092543601&partnerID=8YFLogxK
U2 - 10.1109/JMEMS.2020.3011196
DO - 10.1109/JMEMS.2020.3011196
M3 - Article
SN - 1057-7157
VL - 29
SP - 881
EP - 887
JO - IEEE Journal of Microelectromechanical Systems
JF - IEEE Journal of Microelectromechanical Systems
IS - 5
ER -