课程文献中心 更多>>

关键词： Microcarriers   Mesenchymal Stem Cell   Bioreactors  

摘要： 1253

关键词： hydrodynamic conditions   scalable vertical-wheel bioreactor   spherical cell aggregate  

摘要： 706

关键词： mathematical process models   model-assisted scale-up   Monte Carlo uncertainty analysis   quality by design  

摘要： Miniaturized bioreactor (MBR) systems are routinely used in the development of mammalian cell culture processes. However, scale-up of process strategies obtained in MBR- to larger scale is challenging due to mainly non-holistic scale-up approaches. In this study, a model-based workflow is introduced to quantify differences in the process dynamics between bioreactor scales and thus enable a more knowledge-driven scale-up. The workflow is applied to two case studies with antibody-producing Chinese hamster ovary cell lines. With the workflow, model parameter distributions are estimated first under consideration of experimental variability for different scales. Second, the obtained individual model parameter distributions are tested for statistical differences. In case of significant differences, model parametric distributions are transferred between the scales. In case study I, a fed-batch process in a microtiter plate (4 ml working volume) and lab-scale bioreactor (3750 ml working volume) was mathematically modeled and evaluated. No significant differences were identified for model parameter distributions reflecting process dynamics. Therefore, the microtiter plate can be applied as scale-down tool for the lab-scale bioreactor. In case study II, a fed-batch process in a 24-Deep-Well-Plate (2 ml working volume) and shake flask (40 ml working volume) with two feed media was investigated. Model parameter distributions showed significant differences. Thus, process strategies were mathematically transferred, and model predictions were simulated for a new shake flask culture setup and confirmed in validation experiments. Overall, the workflow enables a knowledge-driven evaluation of scale-up for a more efficient bioprocess design and optimization.

关键词： bioreactor   mesenchymal stem/stromal cells   GMP  

摘要： 1245

关键词： Cell Therapy - ES Cells and iPS Cells   Induced Pluripotent Stem Cells   Cell Processing  

摘要： 705

关键词： Simulation   Computational fluid dynamics (CFD)   Anaerobic digestion   Packed-bed bioreactor   Volatile fatty acids  

摘要： -In this study, a lab-scale continuous packed-bed bioreactor with multi-sized distributed particles has been simulated in a structured layout using computational fluid dynamics. The goal was to achieve a well-estimated simple model which can describe the hydrodynamic regime of flow as well as mass transfer of species within the bioreactor. A MATLAB program was coded to create the packed-bed geometry by generating non-overlapping spherical particles. The flow hydrodynamics was assumed to be single-phase creeping flow regime (Stokes flow). The kinetic data of batch experiments at similar operating conditions were used to formulate the rate of anaerobic reactions. The anaerobic methano-genesis reactions were assumed to occur at the particle surfaces (on the biofllm). The bioreactor temperature was fixed at 37 degrees C. The commercial software COMSOL Multiphysics 5.0 was employed to solve the governing equations. Velocity profiles and concentration distribution of volatile fatty acids (VFAs) are shown inside the packed-bed reactor. Simulation results were found to be in good agreement with the experimental data at various influent flow rates (23.8 - 43.5 mL/h) and various influent concentrations of VFAs (0.001 - 0.042 M). In all cases, the relative error was less than 15% which is acceptable. This proposed model is applicable for scale-up and optimization purposes as well as evaluation of other kinetic models. (C) 2021 Elsevier Ltd. All rights reserved.

关键词： Lentivirus   Scale-Up   iCELLis  

摘要： 1108

关键词： DNA   RNA   bioactive compounds   excipients   surfactants   mouthwash   oral gels   oxidative stress   reconstituted oral epithelium   bioreactors  

摘要： Background: DNA-RNA compounds have shown promising protection against cell oxidative stress. This study aimed to assess the cytotoxicity, protective, or preventive effect of different experimental formulations on oral epithelia's oxidative stress in vitro. Methods: Reconstituted human oral epithelia (RHOE) were grown air-lifted in a continuous-flow bioreactor. Mouthwashes and gels containing DNA-RNA compounds and other bioactive molecules were tested on a model of oxidative stress generated by hydrogen peroxide treatment. Epithelia viability was evaluated using a biochemical MTT-based assay and confocal microscopy;structural and ultrastructural morphology was evaluated by light microscopy and TEM. Results: DNA-RNA showed non-cytotoxic activity and effectively protected against oxidative stress, but did not help in its prevention. Gel formulations did not express adequate activity compared to the mouthwashes. Excipients played a fundamental role in enhancing or even decreasing the bioactive molecules' effect. Conclusion: A mouthwash formulation with hydrolyzed DNA-RNA effectively protected against oxidative stress without additional enhancement by other bioactive molecules. Active compounds, such as hyaluronic acid, beta-Glucan, allantoin, bisabolol, ruscogenin, and essential oils, showed a protective effect against oxidative stress, which was not synergistic with the one of DNA-RNA. Incorporation of surfactant agents showed a reduced, yet significant, cytotoxic effect.

关键词： Bioreactor   Microcarrier   Mesenchymal Stem Cell  

摘要： 119

关键词： S. cerevisiae   Bioethanol   Unconventional bioreactor   Magnetic field   H+ efflux   P-type H+-ATPase  

摘要： The aim of this work was to evaluate the bioethanol productivity in an unconventional bioreactor assisted by extremely low frequency (ELF) - electromagnetic field and elucidate the biophysical mechanism of action by which ELF magnetic fields improve the bioethanol production by S. cerevisiae. Fermentations were carried out under axial field lines at 10 mT magnetic flux density (B), using three different recycling arrangements (spiral-shape tube, u-shape tube and whole bioreactor) in a closed loop. Fermentation kinetics were monitored by cell growth, substrate consumption, ethanol and by-product formation. In addition, electrophysiological measurements of the H+ ion fluxes were carried out in yeast cells sampled at different fermentation stages. ELF magnetic fields increased the glucose uptake, bioethanol production and H+ efflux, shortening in 2 h the fermentation time. The greatest effects of the ELF magnetic fields were obtained in the whole bioreactor arrangement, reaching an average increase of 33% in the bioethanol production. The results are consistent with a stimulatory effect of ELF magnetic fields on the plasma membrane H+-ATPase activity, as indicated by the specific increase of the vanadate-sensitive component of the yeast cells H+ efflux, providing a new biophysical mechanism of action for the biological effect of magnetic fields. (C) 2021 Elsevier Ltd. All rights reserved.