@article {2991,
	title = {On the adhesion-cohesion balance and oxygen consumption characteristics of liver organoids},
	journal = {Plos One},
	year = {2017},
	month = {03/2017},
	abstract = {<p class="rtejustify">Liver organoids (LOs) are of interest in tissue replacement, hepatotoxicity and pathophysiological studies. However, it is still unclear what triggers LO self-assembly and what the optimal environment is for their culture. Hypothesizing that LO formation occurs as a result of a fine balance between cell-substrate adhesion and cell-cell cohesion, we used 3 cell types (hepatocytes, liver sinusoidal endothelial cells and mesenchymal stem cells) to investigate LO self-assembly on different substrates keeping the culture parameters (e.g. culture media, cell types/number) and substrate stiffness constant. As cellular spheroids may suffer from oxygen depletion in the core, we also sought to identify the optimal culture conditions for LOs in order to guarantee an adequate supply of oxygen during proliferation and differentiation. The oxygen consumption characteristics of LOs were measured using an O<sub>2</sub> sensor and used to model the O<sub>2</sub> concentration gradient in the organoids. We show that no LO formation occurs on highly adhesive hepatic extra-cellular matrix-based substrates, suggesting that cellular aggregation requires an optimal trade-off between the adhesiveness of a substrate and the cohesive forces between cells and that this balance is modulated by substrate mechanics. Thus, in addition to substrate stiffness, physicochemical properties, which are also critical for cell adhesion, play a role in LO self-assembly.</p>
},
	keywords = {Bioengineering},
	doi = {http://dx.doi.org/10.1371/journal.pone.0173206},
	url = {http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0173206},
	author = {G. Mattei and C. Magliaro and S. Giusti and S. D. Ramachandran and S. Heinz and J. Braspenning and A. Ahluwalia}
}
@conference {2278,
	title = {Autonomous bioreactor modules for disease models and detection of systemic toxicity},
	booktitle = {ALTEX Proceedings},
	year = {2014},
	pages = {43},
	address = {Prague, Czech Republic},
	abstract = {<p>Advanced systems based on bioreactors and scaffolds are an essential step towards the development of more predictive and ethical alternatives to animal experiments. Size, modularity, automation, monitoring and essential design are crucial because these elements will ease the transition from old technology and accelerate their acceptance into mainstream research. Based on these requirements, the interconnected transparent sensorised {\^a}{\texteuro}{\oe}lego{\^a}{\texteuro} bioreactors designed in our labs have been used to generate physiologically relevant disease and toxicity models which recapitulate systemic responses impossible to observe in standard cell cultures. The disease model is an interconnected bioreactor circuit with i) adipose tissue in 3D in 3 different concentrations representing normo-weight, over weight and obese body mass indices, ii) human hepatocytes on porous collagen scaffolds and iii) monolayers of human endothelial cells. High adiposity and elevated glucose levels induce systemic and endothelial inflammation in the circuit, as observed in overweight and diabetic humans (Iori et al., 2012). Using similar technology a three-tissue circuit for monitoring the absorption, distribution, metabolism and toxicity of nanoparticles was developed in the context of the EU project InLiveTox (Ucciferri et al., 2014). The results were strikingly similar to those observed in animal experiments demonstrating that the dynamic 3D in-vitro models are ethical, meaningful and economically viable replacements.</p>
},
	keywords = {Bioengineering},
	author = {A. Ahluwalia and S. Giusti and Sbrana, T. and M. Wilkinson and A. Misto and Lehr, C.-M. and M. Liley},
	editor = {S. Horst and D. J{\'\i}rov{\'a}}
}
