On June 6th 2023 Milica Dostanic successfully defended her thesis, entitled: ‘Miniature sensorized platform for engineered heart tissues’ at Delft University of Technology. Her research was performed under the supervision of Lina Sarro and Massimo Mastrangeli from the faculty of Electrical Engineering, Mathematics and Computer Science.
Engineered Heart Tissues (EHTs) are promising 3D in vitro models aiming at recapitulating the (patho)physiology of adult human myocardium. Development of these models requires the symbiotic effort of many disciplines, such as biology, engineering, physics, chemistry, etc. Within this dissertation, an artificial dynamic microenvironment has been developed to facilitate the formation and promote maturation of EHTs assembled of three different iPSC-derived cardiac cell types.
The platform development was realized within several steps. First, the mechanical support for the tissue formation was created in the form of two elastic micropillars, made of PDMS, within the elliptic well. Fine-tuning of the micropillar geometry enabled control over tissue formation position and experiment reproducibility. Contractile force readouts were incorporated using optical (external) and electrical (integrated) methods. A stand-alone app was developed for optical tracking of the tip displacement of bending micropillars. Electrical force measurement was achieved by integrating a pair of co-planar capacitive sensors within the PDMS substrate below the pillars. The requirements for electrical stimulation of tissues were met by incorporating a pair of pacing microelectrodes within the platform. Finally, the developed single-chip platform was upscaled into a multi-well plate format. The developed system represents a step towards the dynamic microenvironment that could provide needed stimuli to the EHTs and monitor its formation and maturation in an automated manner.
