02268nas a2200229   4500008003900000245008800039210006900127260002700196300000700223520152800230653001901758100001801777700001401795700001401809700001801823700001401841700001501855700001401870700001401884700001701898856012301915       2014                          d00aAutonomous bioreactor modules for disease models and detection of systemic toxicity0 aAutonomous bioreactor modules for disease models and detection o  aPrague, Czech Republic  a433 a<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 â€œlegoâ€ 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>
10aBioengineering1 aAhluwalia, A.1 aGiusti, S1 aSbrana, T1 aWilkinson, M.1 aMisto, A.1 aLehr, C -M1 aLiley, M.1 aHorst, S.1 aJírová, D.  uhttp://118699.obes.asia/publications/autonomous-bioreactor-modules-disease-models-and-detection-systemic-toxicity.html01787nas a2200205   4500008004100000022001400041245013800055210006900193520112600262653001901388100001701407700001701424700001401441700001501455700001301470700001701483700001501500700001801515856004801533       2013                        eng d  a1743-540400aIn vitro toxicological screening of nanoparticles on primary human endothelial cells and the role of flow in modulating cell response0 aIn vitro toxicological screening of nanoparticles on primary hum3 a<p>Abstract After passage through biological barriers, nanomaterials inevitably end up in contact with the vascular endothelium and physiological flow, and can induce cardiovascular damage. In this study the toxicity and sublethal effects of 6 nanoparticles, including 4 of industrial and biomedical importance, on human endothelial cells was investigated using different in vitro assays. The results show that all the particles investigated induce some level of damage to the cells and that silver particles were most toxic, followed by titanium dioxide. Furthermore endothelial cells were shown to be more susceptible when exposed to silver nanoparticles under flow conditions in a bioreactor. The study underlines that although simple in vitro tests are useful to screen compounds and to identify the type of effect induced on cells, they may not be sufficient to define safe exposure limits. Therefore, once initial toxicity screening has been conducted on nanomaterials, it is necessary to develop more physiologically relevant in vitro models to better understand how nanomaterials can impact on human health.</p>
10aBioengineering1 aUcciferri, N1 aCollnot, E M1 aGaiser, B1 aTirella, A1 aStone, V1 aDomenici, C.1 aLehr, C -M1 aAhluwalia, A.  uhttp://www.ncbi.nlm.nih.gov/pubmed/23909703