A Miniaturized EHT Platform for Accurate Measurements of Tissue Contractile Properties
M. Dostanic (TU Delft - Electronic Components, Technology and Materials)
Jeroen Stein (Leiden University Medical Center)
Laura Windt (Leiden University Medical Center)
Berend van Meer (Leiden University Medical Center)
Milena Bellin (Università degli Studi di Padova, Leiden University Medical Center)
Valeria Orlova (Leiden University Medical Center)
Massimo Mastrangeli (TU Delft - Electronic Components, Technology and Materials)
Christine Mummery (Leiden University Medical Center)
Pasqualina M Sarro (TU Delft - Electronic Components, Technology and Materials)
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Abstract
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.
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