Generation, probing, and biophysical stimulation of human microtissues in microfluidic Organ-on-Chip platforms

Abstract

Over the last decade Organ-on-Chip (OoC) emerged as disruptive technology combining aspects of microfluidics and tissue engineering. OoCs culture human tissues in tailored microenvironments under microfluidic perfusion, yielding an unprecedented recapitulation of human physiology. So far, most systems predominantly focus on physiological tissue generation. However, it is crucial to integrate stimulation and readout capabilities, leveraging OoCs from bare tissue generation tools to advanced integrated experimental platforms. This thesis focuses on the development and characterization of novel microphysiological systems to probe and actuate tissues on the microscale. We present two Heart-on-Chip platforms enabling the generation of aligned cardiac muscle fibers and investigate the integration of force and O2 sensing as well as electrical stimulation capabilities. Furthermore, we introduce and characterize two OoCs enabling the precise delivery of biomechanical stretch and compression stimuli. All in all, the systems developed in the framework of this thesis provide a flexible toolkit amenable for disease modeling or personalized medicine, offering advanced experimental capabilities for manipulating and interrogating integrated tissues.