A versatile bioreactor suitable for dynamic suspension cell culture under tunable shear stress conditions has been developed and preliminarily tested culturing cancer cell spheroids. By adopting simple technological solutions and avoiding rotating components, the bioreactor exploits the laminar hydrodynamics establishing within the culture chamber enabling dynamic cell suspension in an environment favourable to mass transport, under a wide range of tunable shear stress conditions. The design phase of the device has been supported by multiphysics modelling and has provided a comprehensive analysis of the operating principles of the bioreactor. Moreover, an explanatory example is herein presented with multiphysics simulations used to set the proper bioreactor operating conditions for preliminary in vitro biological tests on a human lung carcinoma cell line. The biological results demonstrate that the ultralow shear dynamic suspension provided by the device is beneficial for culturing cancer cell spheroids. In comparison to the static suspension control, dynamic cell suspension preserves morphological features, promotes intercellular connection, increases spheroid size (2.4-fold increase) and number of cycling cells (1.58-fold increase), and reduces double strand DNA damage (1.5-fold reduction). It is envisioned that the versatility of this bioreactor could allow investigation and expansion of different cell types in the future.
A49 increased skin autofl uorescence and rate of increase. By not being infl uenced by single dialysis sessions, SAF shows to be a useful marker for assessing AGE accumulation and studying the related CV risk in HD patients. O1 (EI0222)Objectives: To measure annual increase in skin autofl uorescence (AF), a marker of accumulation of Advanced Glycation end products (AGEs) in the skin of hemodialysis (HD) patients and various plasma markers including heart-type fatty acid binding protein (H-FABP) in order to fi nd factors that can predict the mortality of HD patients. Materials and Methods: One hundred sixty-nine HD patients were enrolled in a clinical prospective study. Skin AF was measured at 4 time points at approximately 6 months intervals. At the same time points the routine blood chemistry and plasma markers of oxidative stress (Superoxide Dismutase and Myeloperoxydase), infl ammation (C-Reactive Protein: CRP), endothelial activation (intercellular Adhesion Molecule-1: ICAM-1 and von Willebrand Factor) and myocardial and kidney damage (H-FABP) were measured. The entire study lasted 32 months. Results: Skin AF was increased in HD patients, especially in those with diabetes, in which it showed to be the sole independent marker of the presence of cardiovascular diseases (CVD). The mean annual increase of Skin AF (ΔAF) was 0.15 ± 0.09 AU (mean ± standard error). Seasonal fl uctuations in Skin AF with a mean of 0.31 ± 0.10 AU (mean ± standard error) were only present in patients with Hepatitis C. In the multivariate Cox regression analysis we found that age diabetes, hypertension, annual ΔAF and values of CRP, ICAM-1 and H-FABP at the start of the study were independent predictors of overall mortality. Strong predictors of CVD mortality were age, diabetes, male gender, annual ΔAF and H-FABP and albumins. Moreover, combined use of annual ΔAF and single measurement H-FABP gives even better results in the prediction of the CVD mortality risk than separate use. Conclusions: Annual ΔAF and single measurement of H-FABP are strong independent predictors of overall and CVD mortality in HD patients.Objectives: Advanced glycation endproducts (AGEs) accumulate in all human subjects, e.g. in the skin. Because part of the AGEs shows autofl uorescence, skin autofl uorescence (SAF) generally increases with calendar age. SAF values above normal have been reported in patients with cardiovascular (CV) risk. SAF was a strong marker of CV mortality in hemodialysis (HD) patients [Meerwaldt, JASN 2005]. High levels of plasma AGEs were reported as well in HD patients compared to control subjects [Floridi, NDT 2002]. A consortium was formed to study the use of SAF for measuring the effectiveness of interventions that aim to decrease (CV) risk in dialysis patients. Methods: SAF was measured non-invasively with the AGE Reader (DiagnOptics Technologies B.V., Groningen, The Netherlands) at the inner forearm in HD patients: 33 (Umeå), 170 (Skopje), and 109 (Groningen). In Umeå and Skopje measurements were repeated at least twice a year for 15...
Recent research on biological materials and bioartificial systems has created one of the most dynamic field at the confluence of physical sciences, molecular engineering, cell biology, materials sciences, biotechnology and (nano) medicine. This field concerns better understanding of living systems, design of bio-inspired materials, synthesis of bioartificial technologies with new properties depending on their multi-scale architectures. Biological and man-made systems show the first level of organization at the nanoscale, where the fundamental properties and functions are settled (e.g., proteome and genome). The nanoscale properties reflect on larger scales: mesoscale, microscale, and continuum. Mechanisms by which phenomena at the different length and time scales are coupled and influence each other is the central issue in linking properties to functionalities, with a dramatic impact in designing and engineering biosystems. To get insights into the progressive trough-scales cascade effects-from molecular to macroscale level and from nanoseconds to life expectancy duration-multiscale/multiphysics models are required, dealing with inorganic, biological and hybrid matter. Thus, bioartificial systems technology depends upon our ability in assembling molecules into objects, hierarchically along several length scales, and in disassembling objects into molecules, in a tailored manner. As a peculiar feature, in bioartificial systems, the definition of the interactions between artificial and biological components needs to incorporate the “time” variable, in order to reproduce the evolution of the overall system, and to simulate complex phenomena as biodegradation and tissue remodeling. Herein, a number of paradigmatic multiscale models that attend the investigation of biological systems and the engineering of bioartificial systems is reviewed and discussed.
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