A high‐throughput microfluidic microphysiological system (PREDICT‐96) to recapitulate hepatocyte function in dynamic flow conditions

Abstract

Microphysiological systems (MPSs) are dynamic cell culture platforms that incorporate mechanical and chemical cues to recapitulate organ‐specific functions and architecture. Recent advances in microfabrication technologies and processes have enabled the development of enhanced in vitro models that capture human physiology more accurately while increasing throughput and reducing material‐based technical artifacts. A common candidate for MPS development is liver due to its crucial role in drug metabolism, inflammation and human disease. While several liver‐on‐chip models exist, few studies have combined long term culture with dynamic inputs, such as media flow, in a high‐throughput format. Herein, we have developed an oxygen permeable, high‐throughput (96‐well form factor), thermoplastic MPS (PREDICT‐96 array) integrated with an on‐board, ultra‐low volume, recirculating pumping system (PREDICT‐96 pump) to facilitate media flow in the system; collectively, these technologies comprise the PREDICT‐96 platform. To demonstrate usability of the PREDICT‐96 array, we introduce PHHs using standard handling procedures for multi‐well plates and maintain viable culture for up to 14 days. By incorporating media flow to mimic in vivo mass transport, we observe a robust increase in metabolic and secretory functions of PHHs when compared to static culture. The PHHs demonstrate reproducible baseline metabolic activity and secretion markers which underscores the utility of the system for drug screening applications. Furthermore, long‐term culture with fluid flow allows for the periodic introduction of media components (e.g., fatty acids, cytokines) and resolve cellular responses to chronic stimuli over time. The low‐volume footprint of the pump and small media volume in the MPS allow for the interrogation of hepatic responses incorporating secretion feedback to a stimulus, which is essential for disease model development and drug interrogation. We envision future development of this liver model to incorporate key primary hepatic cells, multi‐cellular co‐cultures and integration with high‐throughput analytical tools.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.