An Adaptable Soft-mold Embossing Process for Fabricating Optically-accessible, Microfeature-based Culture Systems and Application toward Liver Stage Antimalarial Compound Testing

Advanced cell culture methods to model organ function have been demonstrated to better replicate in vivo conditions and produce data with improved translational value. Because the liver is parituclarly important to human health, several advanced culture methods exist to experiment with liver disease states, including the infectious disease malaria, which can be better controlled with development of new antimalarials effective against the liver parasite population. We developed a novel fabrication method to emboss hepatocyte-confining microfeatures into polysytrene, resulting in microfeature-based hepatocyte confinement (µHEP) slides and plates. RNAseq of hepatocytes in µHEP systems demonstrated microfeatures sustain hepatic differentiation and function, suggesting broader utility for preclinical hepatic assays; while our tailorable embossing process could be repurposed for developing additional organ models. Overall design: Examination of primary human hepatocyte transcriptome in different culture platforms