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A mathematical model for a granular biofilm reactor for leachate treatment was validated by long-term measured data to investigate the mechanisms and drivers influencing biological nitrogen removal and microbial consortia dynamics. The proposed model, based on Activated Sludge Model (ASM1), included anaerobic ammonium oxidation (anammox), nitrifying and heterotrophic denitrifying bacteria which can attach and grow on granular activated carbon (GAC) particles. Two kinetic descriptions for the model were proposed: with and without soluble microbial products (SMP) and extracellular polymeric substance (EPS). The model accuracy was checked using recorded total inorganic nitrogen concentrations in the effluent and estimated relative abundance of active bacteria using quantitative fluorescence in-situ hybridization (qFISH). Results suggested that the model with EPS kinetics fits better for the relative abundance of anammox bacteria and nitrifying bacteria compared to the model without EPS. The model with EPS and SMP confirms that the growth and existence of heterotrophs in anammox biofilm systems slightly increased due to including the kinetics of SMP production in the model. During the one-year simulation period, the fractions of autotrophs and EPS in the biomass were almost stable but the fraction of heterotrophs decreased which is correlated with the reduction in nitrogen surface loading on the biofilm.

In cellular, tissue-level or whole organ bioreactors, the level of dissolved oxygen is one of the most important factors requiring control. Hypoxic environments may lead to cellular apoptosis, while hyperoxic environments may lead to cellular damage or dedifferentiation, both resulting in loss of overall tissue function. This manuscript describes the creation, characterization and validation of a bioreactor system that can control oxygen delivery based on real-time metabolic demand of cultured whole lung tissue. A mathematical model describing and predicting gas exchange within the tunable bioreactor system is developed. In addition, the inherent gas exchange properties of the bioreactor and the inherent oxygen consumption rates of native rat lungs are determined, thereby providing a quantitative relationship between system parameters and levels of dissolved oxygen. Finally, the mathematical model is validated during whole lung culture under a range of system parameters. The system presented here provides a quantitative relationship between the concentration of dissolved oxygen, tissue oxygen consumption rates, and controllable system parameters that introduce gasses into the bioreactor. This relationship not only enables the maintenance of constant levels of dissolved oxygen throughout a culture period during which cells are replicating, but also provides noninvasive and real-time estimation of the metabolic and proliferative states of native or engineered lung tissue simply through dissolved oxygen measurements. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

Endothelial cells (ECs) exist in different microenvironments in vivo, including under different levels of shear stress in arteries versus veins. Standard stem cell differentiation protocols to derive ECs and EC-subtypes from human induced pluripotent stem cells (hiPSCs) generally use growth factors or other soluble factors in an effort to specify cell fate. In this study, a biomimetic flow bioreactor was used to subject hiPSC-derived ECs (hiPSC-ECs) to shear stress to determine the impacts on phenotype and upregulation of markers associated with an anti-thrombotic, anti-inflammatory, arterial-like phenotype. The in vitro bioreactor system was able to efficiently mature hiPSC-ECs into arterial-like cells in 24 h, as demonstrated by qRT-PCR for arterial markers EphrinB2, CXCR4, Conexin40 and Notch1, as well protein-level expression of Notch1 intracellular domain (NICD). Furthermore, the exogenous addition of soluble factors was not able to fully recapitulate this phenotype that was imparted by shear stress exposure. The induction of these phenotypic changes was biomechanically mediated in the shear stress bioreactor. This biomimetic flow bioreactor is an effective means for the differentiation of hiPSC-ECs toward an arterial-like phenotype, and is amenable to scale-up for culturing large quantities of cells for tissue engineering applications., (Copyright © 2015 Elsevier Ltd. All rights reserved.)