Engineered Platforms for Maturing Pluripotent Stem Cell-Derived Liver Cells for Disease Modeling.

Several liver diseases (eg, hepatitis B/C viruses, alcoholic/nonalcoholic fatty liver, malaria, monogenic diseases, and drug-induced liver injury) significantly impact global mortality and morbidity. Species-specific differences in liver functions limit the use of animals to fully elucidate/predict human outcomes; therefore, in vitro human liver models are used for basic and translational research to complement animal studies. However, primary human liver cells are in short supply and display donor-to-donor variability in viability/quality. In contrast, human hepatocyte-like cells (HLCs) differentiated from induced pluripotent stem cells and embryonic stem cells are a near infinite cell resource that retains the patient/donor's genetic background; however, conventional protocols yield immature phenotypes. HLC maturation can be significantly improved using advanced techniques, such as protein micropatterning to precisely control cell-cell interactions, controlled sized spheroids, organoids with multiple cell types and layers, 3-dimensional bioprinting to spatially control cell populations, microfluidic devices for automated nutrient exchange and to induce liver zonation via soluble factor gradients, and synthetic biology to genetically modify the HLCs to accelerate and enhance maturation. Here, we present design features and characterization for representative advanced HLC maturation platforms and then discuss HLC use for modeling various liver diseases. Lastly, we discuss desirable advances to move this field forward. We anticipate that with continued advances in this space, pluripotent stem cell-derived liver models will provide human-relevant data much earlier in preclinical drug development and reduce animal usage, help elucidate liver disease mechanisms for the discovery of efficacious and safe therapeutics, and be useful as cell-based therapies for patients suffering from end-stage liver failure.

3DµF - Interactive Design Environment for Continuous Flow Microfluidic Devices.

The design of microfluidic Lab on a Chip (LoC) systems is an onerous task requiring specialized skills in fluid dynamics, mechanical design drafting, and manufacturing. Engineers face significant challenges during the labor-intensive process of designing microfluidic devices, with very few specialized tools that help automate the process. Typical design iterations require the engineer to research the architecture, manually draft the device layout, optimize for manufacturing processes, and manually calculate and program the valve sequences that operate the microfluidic device. The problem compounds when engineers not only have to test the functionality of the chip but are also expected to optimize them for the robust execution of biological assays. In this paper, we present an interactive tool for designing continuous flow microfluidic devices. 3DµF is the first completely open source interactive microfluidic system designer that readily supports state of the art design automation algorithms. Through various case studies, we show 3DµF can be used to reproduce designs from literature, provide metrics for evaluating microfluidic design complexity and showcase how 3DµF is a platform for integrating a wide assortment of engineering techniques used in the design of microfluidic devices as a part of the standard design workflow.