Bioreactors: Tools or devices for generating products using the synthetic or chemical conversion capacity of a biological system. They can be classical fermentors, cell culture perfusion systems, or enzyme bioreactors. For production of proteins or enzymes, recombinant microorganisms such as bacteria, mammalian cells, or insect or plant cells are usually chosen.Waste Disposal, Fluid: The discarding or destroying of liquid waste products or their transformation into something useful or innocuous.Tissue Engineering: Generating tissue in vitro for clinical applications, such as replacing wounded tissues or impaired organs. The use of TISSUE SCAFFOLDING enables the generation of complex multi-layered tissues and tissue structures.Batch Cell Culture Techniques: Methods for cultivation of cells, usually on a large-scale, in a closed system for the purpose of producing cells or cellular products to harvest.Cell Culture Techniques: Methods for maintaining or growing CELLS in vitro.Biological Oxygen Demand Analysis: Testing for the amount of biodegradable organic material in a water sample by measuring the quantity of oxygen consumed by biodegradation of those materials over a specific time period.Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., GENETIC ENGINEERING) is a central focus; laboratory methods used include TRANSFECTION and CLONING technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction.Liver, Artificial: Devices for simulating the activities of the liver. They often consist of a hybrid between both biological and artificial materials.Waste Water: Contaminated water generated as a waste product of human activity.Tissue Scaffolds: Cell growth support structures composed of BIOCOMPATIBLE MATERIALS. They are specially designed solid support matrices for cell attachment in TISSUE ENGINEERING and GUIDED TISSUE REGENERATION uses.Industrial Microbiology: The study, utilization, and manipulation of those microorganisms capable of economically producing desirable substances or changes in substances, and the control of undesirable microorganisms.Weightlessness Simulation: Condition under normal Earth gravity where the force of gravity itself is not actually altered but its influence or effect may be modified and studied. (From ASGSB Bull 1992;5(2):27)Microbial Consortia: A group of different species of microorganisms that act together as a community.Sewage: Refuse liquid or waste matter carried off by sewers.Flow Injection Analysis: The analysis of a chemical substance by inserting a sample into a carrier stream of reagent using a sample injection valve that propels the sample downstream where mixing occurs in a coiled tube, then passes into a flow-through detector and a recorder or other data handling device.Biodegradation, Environmental: Elimination of ENVIRONMENTAL POLLUTANTS; PESTICIDES and other waste using living organisms, usually involving intervention of environmental or sanitation engineers.Water Purification: Any of several processes in which undesirable impurities in water are removed or neutralized; for example, chlorination, filtration, primary treatment, ion exchange, and distillation. It includes treatment of WASTE WATER to provide potable and hygienic water in a controlled or closed environment as well as provision of public drinking water supplies.Cupriavidus necator: A gram-negative, facultatively chemoautotrophic bacterium, formerly called Wautersia eutropha, found in water and soil.Comamonadaceae: A family of gram-negative aerobic bacteria in the class BETA PROTEOBACTERIA, encompassing the acidovorans rRNA complex. Some species are pathogenic for PLANTS.Disposable Equipment: Apparatus, devices, or supplies intended for one-time or temporary use.Fermentation: Anaerobic degradation of GLUCOSE or other organic nutrients to gain energy in the form of ATP. End products vary depending on organisms, substrates, and enzymatic pathways. Common fermentation products include ETHANOL and LACTIC ACID.Polyglycolic Acid: A biocompatible polymer used as a surgical suture material.Biomass: Total mass of all the organisms of a given type and/or in a given area. (From Concise Dictionary of Biology, 1990) It includes the yield of vegetative mass produced from any given crop.Equipment Design: Methods of creating machines and devices.Sphingomonas: A genus of gram-negative, aerobic, rod-shaped bacteria characterized by an outer membrane that contains glycosphingolipids but lacks lipopolysaccharide. They have the ability to degrade a broad range of substituted aromatic compounds.Equipment Failure Analysis: The evaluation of incidents involving the loss of function of a device. These evaluations are used for a variety of purposes such as to determine the failure rates, the causes of failures, costs of failures, and the reliability and maintainability of devices.Bacteria: One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive.Tissue Culture Techniques: A technique for maintaining or growing TISSUE in vitro, usually by DIFFUSION, perifusion, or PERFUSION. The tissue is cultured directly after removal from the host without being dispersed for cell culture.Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as AGAR or GELATIN.Cartilage: A non-vascular form of connective tissue composed of CHONDROCYTES embedded in a matrix that includes CHONDROITIN SULFATE and various types of FIBRILLAR COLLAGEN. There are three major types: HYALINE CARTILAGE; FIBROCARTILAGE; and ELASTIC CARTILAGE.Polyesters: Polymers of organic acids and alcohols, with ester linkages--usually polyethylene terephthalate; can be cured into hard plastic, films or tapes, or fibers which can be woven into fabrics, meshes or velours.Anaerobiosis: The complete absence, or (loosely) the paucity, of gaseous or dissolved elemental oxygen in a given place or environment. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Chondrogenesis: The formation of cartilage. This process is directed by CHONDROCYTES which continually divide and lay down matrix during development. It is sometimes a precursor to OSTEOGENESIS.Methane: The simplest saturated hydrocarbon. It is a colorless, flammable gas, slightly soluble in water. It is one of the chief constituents of natural gas and is formed in the decomposition of organic matter. (Grant & Hackh's Chemical Dictionary, 5th ed)Biocompatible Materials: Synthetic or natural materials, other than DRUGS, that are used to replace or repair any body TISSUES or bodily function.Microtechnology: Manufacturing technology for making microscopic devices in the micrometer range (typically 1-100 micrometers), such as integrated circuits or MEMS. The process usually involves replication and parallel fabrication of hundreds or millions of identical structures using various thin film deposition techniques and carried out in environmentally-controlled clean rooms.Holography: The recording of images in three-dimensional form on a photographic film by exposing it to a laser beam reflected from the object under study.Nerium: A plant genus of the family APOCYNACEAE. It is a very poisonous plant that contains cardioactive agents.Liquid Crystals: Materials in intermediate state between solid and liquid.Dimethylpolysiloxanes: Silicone polymers which consist of silicon atoms substituted with methyl groups and linked by oxygen atoms. They comprise a series of biocompatible materials used as liquids, gels or solids; as film for artificial membranes, gels for implants, and liquids for drug vehicles; and as antifoaming agents.Biofuels: Hydrocarbon-rich byproducts from the non-fossilized BIOMASS that are combusted to generate energy as opposed to fossilized hydrocarbon deposits (FOSSIL FUELS).EnglandExhibits as Topic: Discussions, descriptions or catalogs of public displays or items representative of a given subject.Smoke-Free Policy: Prohibition against tobacco smoking in specific areas to control TOBACCO SMOKE POLLUTION.Thoracoscopes: Endoscopes for examining the pleural cavity.Anura: An order of the class Amphibia, which includes several families of frogs and toads. They are characterized by well developed hind limbs adapted for jumping, fused head and trunk and webbed toes. The term "toad" is ambiguous and is properly applied only to the family Bufonidae.Equipment Reuse: Further or repeated use of equipment, instruments, devices, or materials. It includes additional use regardless of the original intent of the producer as to disposability or durability. It does not include the repeated use of fluids or solutions.Webcasts as Topic: Transmission of live or pre-recorded audio or video content via connection or download from the INTERNET.Newspapers: Publications printed and distributed daily, weekly, or at some other regular and usually short interval, containing news, articles of opinion (as editorials and letters), features, advertising, and announcements of current interest. (Webster's 3d ed)Psychology, Applied: The science which utilizes psychologic principles to derive more effective means in dealing with practical problems.Mass Media: Instruments or technological means of communication that reach large numbers of people with a common message: press, radio, television, etc.Blogging: Using an INTERNET based personal journal which may consist of reflections, comments, and often hyperlinks.

Antisense RNA strategies for metabolic engineering of Clostridium acetobutylicum. (1/1439)

We examined the effectiveness of antisense RNA (as RNA) strategies for metabolic engineering of Clostridium acetobutylicum. Strain ATCC 824(pRD4) was developed to produce a 102-nucleotide asRNA with 87% complementarity to the butyrate kinase (BK) gene. Strain ATCC 824(pRD4) exhibited 85 to 90% lower BK and acetate kinase specific activities than the control strain. Strain ATCC 824(pRD4) also exhibited 45 to 50% lower phosphotransbutyrylase (PTB) and phosphotransacetylase specific activities than the control strain. This strain exhibited earlier induction of solventogenesis, which resulted in 50 and 35% higher final concentrations of acetone and butanol, respectively, than the concentrations in the control. Strain ATCC 824(pRD1) was developed to putatively produce a 698-nucleotide asRNA with 96% complementarity to the PTB gene. Strain ATCC 824(pRD1) exhibited 70 and 80% lower PTB and BK activities, respectively, than the control exhibited. It also exhibited 300% higher levels of a lactate dehydrogenase activity than the control exhibited. The growth yields of ATCC 824(pRD1) were 28% less than the growth yields of the control. While the levels of acids were not affected in ATCC 824(pRD1) fermentations, the acetone and butanol concentrations were 96 and 75% lower, respectively, than the concentrations in the control fermentations. The lower level of solvent production by ATCC 824(pRD1) was compensated for by approximately 100-fold higher levels of lactate production. The lack of any significant impact on butyrate formation fluxes by the lower PTB and BK levels suggests that butyrate formation fluxes are not controlled by the levels of the butyrate formation enzymes.  (+info)

Steady-state nitrogen isotope effects of N2 and N2O production in Paracoccus denitrificans. (2/1439)

Nitrogen stable-isotope compositions (delta15N) can help track denitrification and N2O production in the environment, as can knowledge of the isotopic discrimination, or isotope effect, inherent to denitrification. However, the isotope effects associated with denitrification as a function of dissolved-oxygen concentration and their influence on the isotopic composition of N2O are not known. We developed a simple steady-state reactor to allow the measurement of denitrification isotope effects in Paracoccus denitrificans. With [dO2] between 0 and 1.2 microM, the N stable-isotope effects of NO3- and N2O reduction were constant at 28.6 per thousand +/- 1.9 per thousand and 12.9 per thousand +/- 2.6 per thousand, respectively (mean +/- standard error, n = 5). This estimate of the isotope effect of N2O reduction is the first in an axenic denitrifying culture and places the delta15N of denitrification-produced N2O midway between those of the nitrogenous oxide substrates and the product N2 in steady-state systems. Application of both isotope effects to N2O cycling studies is discussed.  (+info)

Immobilization patterns and dynamics of acetate-utilizing methanogens immobilized in sterile granular sludge in upflow anaerobic sludge blanket reactors. (3/1439)

Sterile granular sludge was inoculated with either Methanosarcina mazeii S-6, Methanosaeta concilii GP-6, or both species in acetate-fed upflow anaerobic sludge blanket (UASB) reactors to investigate the immobilization patterns and dynamics of aceticlastic methanogens in granular sludge. After several months of reactor operation, the methanogens were immobilized, either separately or together. The fastest immobilization was observed in the reactor containing M. mazeii S-6. The highest effluent concentration of acetate was observed in the reactor with only M. mazeii S-6 immobilized, while the lowest effluent concentration of acetate was observed in the reactor where both types of methanogens were immobilized together. No changes were observed in the kinetic parameters (Ks and mumax) of immobilized M. concilii GP-6 or M. mazeii S-6 compared with suspended cultures, indicating that immobilization does not affect the growth kinetics of these methanogens. An enzyme-linked immunosorbent assay using polyclonal antibodies against either M. concilii GP-6 or M. mazeii S-6 showed significant variations in the two methanogenic populations in the different reactors. Polyclonal antibodies were further used to study the spatial distribution of the two methanogens. M. concilii GP-6 was immobilized only on existing support material without any specific pattern. M. mazeii S-6, however, showed a different immobilization pattern: large clumps were formed when the concentration of acetate was high, but where the acetate concentration was low this strain was immobilized on support material as single cells or small clumps. The data clearly show that the two aceticlastic methanogens immobilize differently in UASB systems, depending on the conditions found throughout the UASB reactor.  (+info)

The role of benzoate in anaerobic degradation of terephthalate. (4/1439)

The effects of acetate, benzoate, and periods without substrate on the anaerobic degradation of terephthalate (1, 4-benzene-dicarboxylate) by a syntrophic methanogenic culture were studied. The culture had been enriched on terephthalate and was capable of benzoate degradation without a lag phase. When incubated with a mixture of benzoate and terephthalate, subsequent degradation with preference for benzoate was observed. Both benzoate and acetate inhibited the anaerobic degradation of terephthalate. The observed inhibition is partially irreversible, resulting in a decrease (or even a complete loss) of the terephthalate-degrading activity after complete degradation of benzoate or acetate. Irreversible inhibition was characteristic for terephthalate degradation only because the inhibition of benzoate degradation by acetate could well be described by reversible noncompetitive product inhibition. Terephthalate degradation was furthermore irreversibly inhibited by periods without substrate of only a few hours. The inhibition of terephthalate degradation due to periods without substrate could be overcome through incubation of the culture with a mixture of benzoate and terephthalate. In this case no influence of a period without substrate was observed. Based on these observations it is postulated that decarboxylation of terephthalate, resulting in the formation of benzoate, is strictly dependent on the concomitant fermentation of benzoate. In the presence of higher concentrations of benzoate, however, benzoate is the favored substrate over terephthalate, and the culture loses its ability to degrade terephthalate. In order to overcome the inhibition of terephthalate degradation by benzoate and acetate, a two-stage reactor system is suggested for the treatment of wastewater generated during terephthalic acid production.  (+info)

Identification of a novel group of bacteria in sludge from a deteriorated biological phosphorus removal reactor. (5/1439)

The microbial diversity of a deteriorated biological phosphorus removal reactor was investigated by methods not requiring direct cultivation. The reactor was fed with media containing acetate and high levels of phosphate (P/C weight ratio, 8:100) but failed to completely remove phosphate in the effluent and showed very limited biological phosphorus removal activity. Denaturing gradient gel electrophoresis (DGGE) of PCR-amplified 16S ribosomal DNA was used to investigate the bacterial diversity. Up to 11 DGGE bands representing at least 11 different sequence types were observed; DNA from the 6 most dominant of these bands was further isolated and sequenced. Comparative phylogenetic analysis of the partial 16S rRNA sequences suggested that one sequence type was affiliated with the alpha subclass of the Proteobacteria, one was associated with the Legionella group of the gamma subclass of the Proteobacteria, and the remaining four formed a novel group of the gamma subclass of the Proteobacteria with no close relationship to any previously described species. The novel group represented approximately 75% of the PCR-amplified DNA, based on the DGGE band intensities. Two oligonucleotide rRNA probes for this novel group were designed and used in a whole-cell hybridization analysis to investigate the abundance of this novel group in situ. The bacteria were coccoid and 3 to 4 microm in diameter and represented approximately 35% of the total population, suggesting a relatively close agreement with the results obtained by the PCR-based DGGE method. Further, based on electron microscopy and standard staining microscopic analysis, this novel group was able to accumulate granule inclusions, possibly consisting of polyhydroxyalkanoate, inside the cells.  (+info)

Fluorescence in situ hybridization using 16S rRNA-targeted oligonucleotides reveals localization of methanogens and selected uncultured bacteria in mesophilic and thermophilic sludge granules. (6/1439)

16S rRNA-targeted in situ hybridization combined with confocal laser scanning microscopy was used to elucidate the spatial distribution of microbes within two types of methanogenic granular sludge, mesophilic (35 degrees C) and thermophilic (55 degrees C), in upflow anaerobic sludge blanket reactors fed with sucrose-, acetate-, and propionate-based artificial wastewater. The spatial organization of the microbes was visualized in thin sections of the granules by using fluorescent oligonucleotide probes specific to several phylogenetic groups of microbes. In situ hybridization with archaeal- and bacterial-domain probes within granule sections clearly showed that both mesophilic and thermophilic granules had layered structures and that the outer layer harbored mainly bacterial cells while the inner layer consisted mainly of archaeal cells. Methanosaeta-, Methanobacterium-, Methanospirillum-, and Methanosarcina-like cells were detected with oligonucleotide probes specific for the different groups of methanogens, and they were found to be localized inside the granules, in both types of which dominant methanogens were members of the genus Methanosaeta. For specific detection of bacteria which were previously detected by whole-microbial-community 16S ribosomal DNA (rDNA)-cloning analysis (Y. Sekiguchi, Y. Kamagata, K. Syutsubo, A. Ohashi, H. Harada, and K. Nakamura, Microbiology 144:2655-2665, 1998) we designed probes specific for clonal 16S rDNAs related to unidentified green nonsulfur bacteria and clones related to Syntrophobacter species. The probe designed for the cluster closely related to Syntrophobacter species hybridized with coccoid cells in the inner layer of the mesophilic granule sections. The probe for the unidentified bacteria which were clustered with the green nonsulfur bacteria detected filamentous cells in the outermost layer of the thermophilic sludge granule sections. These results revealed the spatial organizations of methanogens and uncultivated bacteria and their in situ morphologies and metabolic functions in both mesophilic and thermophilic granular sludges.  (+info)

High-rate anaerobic treatment of wastewater at low temperatures. (7/1439)

Anaerobic treatment of a volatile fatty acid (VFA) mixture was investigated under psychrophilic (3 to 8 degrees C) conditions in two laboratory-scale expanded granular sludge bed reactor stages in series. The reactor system was seeded with mesophilic methanogenic granular sludge and fed with a mixture of VFAs. Good removal of fatty acids was achieved in the two-stage system. Relative high levels of propionate were present in the effluent of the first stage, but propionate was efficiently removed in the second stage, where a low hydrogen partial pressure and a low acetate concentration were advantageous for propionate oxidation. The specific VFA-degrading activities of the sludge in each of the modules doubled during system operation for 150 days, indicating a good enrichment of methanogens and proton-reducing acetogenic bacteria at such low temperatures. The specific degradation rates of butyrate, propionate, and the VFA mixture amounted to 0.139, 0.110, and 0.214 g of chemical oxygen demand g of volatile suspended solids-1 day-1, respectively. The biomass which was obtained after 1.5 years still had a temperature optimum of between 30 and 40 degrees C.  (+info)

Functional arteries grown in vitro. (8/1439)

A tissue engineering approach was developed to produce arbitrary lengths of vascular graft material from smooth muscle and endothelial cells that were derived from a biopsy of vascular tissue. Bovine vessels cultured under pulsatile conditions had rupture strengths greater than 2000 millimeters of mercury, suture retention strengths of up to 90 grams, and collagen contents of up to 50 percent. Cultured vessels also showed contractile responses to pharmacological agents and contained smooth muscle cells that displayed markers of differentiation such as calponin and myosin heavy chains. Tissue-engineered arteries were implanted in miniature swine, with patency documented up to 24 days by digital angiography.  (+info)

  • In order to take advantage of recent advances in stem cell culture, biomaterials, and tissue engineering techniques, Resodyn Corporation proposes to develop, design, fabricate, and test a multi-functional bioreactor platform system. (sbir.gov)
  • As a starting point for this multi-functional system, Resodyn Corporation will use its highly scalable (50-1,500ml) and successful (>1x108 cells/ml) hypoxia perfusion bioreactor. (sbir.gov)
  • Bose Corporation has introduced the 3DCulturePro™ system, a new multi-specimen perfusion bioreactor designed for biologists, biomedical researchers and scientists who require reproducible and reliable tissue growth. (news-medical.net)
  • This report "Membrane Bioreactor (MBR) Systems Market, By Application (Municipal & Industrial), Type (Hollow Fiber, Flat Sheet & Multi Tubular) & Configuration (Submerged & Sidestream) - Global Trends & Forecasts to 2017" analyses the Membrane bioreactor (MBR) market by geography, applications, configurations, and types of MBR. (benzinga.com)
  • The report also examines the industry in terms of revenue [Million USD] and volume [k MT]. The Membrane Bioreactor Systems market report History Year: 2013-2017 Base Year: 2017 Estimated Year: 2018 Forecast Year 2018 to 2025. (amazingfacts24.com)
  • We utilized custom-designed perfusion bioreactors to culture bone constructs for 5 weeks using a wide range of superficial flow velocities (80, 400, 800, 1,200, and 1,800μm/s), corresponding to estimated initial shear stresses ranging from 0.6 to 20mPa. (elsevier.com)
  • This paper reviews bioreactor designs and their use for protein production under solid state fermentation (SSF) conditions using various agricultural by-products. (ulster.ac.uk)
  • Robinson, T & Singh - Nee Nigam, P 2003, ' Bioreactor design for protein enrichment of agricultural residues by solid state fermentation ', Biochemical Engineering Journal , vol. 13, no. 2-3, S, pp. 197-203. (ulster.ac.uk)
  • My research focuses on woodchip bioreactors - simple trenches that can be constructed on farms to clean the water that flows out of tile drains. (csmonitor.com)
  • Woodchip bioreactors can be installed without requiring farmers to take land out of production, and require very little annual maintenance. (csmonitor.com)
  • Woodchip bioreactors are being implemented for the removal of nitrates in groundwater and tile water drainage. (usda.gov)
  • Woodchip bioreactors are recognized as an effective best management practice in the Iowa Nutrient Reduction Strategy. (usda.gov)
  • Based on that, the single-use bioreactor design phase and the material selection phase are initiated, both closely linked to each other. (bioprocessintl.com)
  • During the past several years, single-use bioreactors have been gradually established in modern biopharmaceutical processes (1, 2). (bioprocessintl.com)
  • Bioreactors are integral to development of high value products and reducing reliance on existing chemical based commodity processes. (mixing-solution.com)
  • Bioreaction engineering is fundamental to the optimization of biotechnological processes and the production of biochemicals by enzymes, microbial, plant and animal cells and higher organisms.A reference text for postgraduate students and researchers in biochemical engineering and bioreactor design, Multiphase Bioreactor Design describes the fundamentals of bioreactors and their increasingly complex varieties. (find-more-books.com)
  • The mass transfer coefficient (k L )and the value of the interfacial area (a), is used to characterize bioreactor systems for their oxygen transfer capability. (ispe.org)
  • Comparisons between the gas phase bioreactors and conventional shaken cultures and sparged liquid bioreactors showed that the gas phase bioreactors offer advantages over the other two systems for the degradation of methane in air. (montana.edu)
  • Continuous optimization, design improvements and characterization of bioreactors are crucial factors placing high demands for innovation in biopharmaceutical manufacturing. (ispe.org)
  • In the biopharmaceutical industry, glass bioreactors are used mainly for process development and optimization, but also scale-down models for process characterization. (bioprocessintl.com)
  • The knowledge obtained in this study provides new insight into the scaffold-based cell culture process in perfusion bioreactors and allows for potential optimization of the cell culture process by regulating the process parameters as well as the scaffold structure during its fabrication. (usask.ca)
  • Perfusion vs. Fed-batch Bioreactors - are there any Differences in Protein Quality? (biotage.com)
  • This led to the interesting comparison between traditional fed-batch bioreactors to perfusion bioreactors for protein quality and productivity. (biotage.com)
  • Also, levels of clipping were significantly lower in the perfusion bioreactor compared to the fed-batch reactor due to lower residence time of the protein inside the bioreactor. (biotage.com)
  • This also led to the distribution of charge variants of the protein being more uniform with higher presence of the main charge variant compared to protein from fed-batch bioreactors. (biotage.com)
  • Perfusion bioreactors have been used to improve the nutrient and gas transfer capabilities and reduce the size limitations inherent to static culture, as well as to modulate cellular responses by hydrodynamic shear. (elsevier.com)