Flow dynamics in bioreactors containing tissue engineering scaffolds.

Bioreactors are widely used in tissue engineering as a way to distribute nutrients within porous materials and provide physical stimulus required by many tissues. However, the fluid dynamics within the large porous structure are not well understood. In this study, we explored the effect of reactor geometry by using rectangular and circular reactors with three different inlet and outlet patterns. Geometries were simulated with and without the porous structure using the computational fluid dynamics software Comsol Multiphysics 3.4 and/or ANSYS CFX 11 respectively. Residence time distribution analysis using a step change of a tracer within the reactor revealed non-ideal fluid distribution characteristics within the reactors. The Brinkman equation was used to model the permeability characteristics with in the chitosan porous structure. Pore size was varied from 10 to 200 microm and the number of pores per unit area was varied from 15 to 1,500 pores/mm(2). Effect of cellular growth and tissue remodeling on flow distribution was also assessed by changing the pore size (85-10 microm) while keeping the number of pores per unit area constant. These results showed significant increase in pressure with reduction in pore size, which could limit the fluid flow and nutrient transport. However, measured pressure drop was marginally higher than the simulation results. Maximum shear stress was similar in both reactors and ranged approximately 0.2-0.3 dynes/cm(2). The simulations were validated experimentally using both a rectangular and circular bioreactor, constructed in-house. Porous structures for the experiments were formed using 0.5% chitosan solution freeze-dried at -80 degrees C, and the pressure drop across the reactor was monitored.

Modeling nutrient consumptions in large flow-through bioreactors for tissue engineering.

Flow-through bioreactors are utilized in tissue regeneration to ensure complete nutrient distribution and apply defined hydrodynamic stresses. The fundamental concepts in designing these bioreactors for regenerating large high aspect ratio tissues (large surface area relative to the thickness of the matrix such as skin, bladder, and cartilage) are not well defined. Further, tissue regeneration is a dynamic process where the porous characteristics change due to proliferation of cells, de novo deposition of matrix components, and degradation of the porous architecture. These changes affect the transport characteristics and there is an imminent need to understand the influence of these factors. Using computational fluid dynamic tools, changes in the pressure drop, shear stress distribution and nutrient consumption patterns during tissue regeneration were assessed in rectangular and circular reactors described by Lawrence et al. [Biotechnol Bioeng 2009;102(3):935-947]. Further, six new designs with different inlet and outlet shapes were analyzed. The fluid flow was defined by the Brinkman equation on the porous regions using the pore characteristics of 85 microm and 120 pores/mm(2). The minimum flow requirements to satisfy nutrient (oxygen and glucose) requirements for three different cell types (SMCs, chondrocytes, and hepatocytes) was evaluated using convective diffusion equation. For consumption reaction, the Michaelis-Menten rate law was used, with constants (k(m) and v(m) values) extracted from literature. Simulations were performed by varying the flow rate as well as the cell number. One of the circular reactors with semicircular inlet and outlet shape decreased (i) non-uniformity in hydrodynamic stress within the porous structure and (ii) non-uniform nutrient distribution. All cell types showed increased consumption of oxygen than glucose. Hepatocytes needed a very high flow rate relative to other cell types. Increase in cell number suggested a need for increasing the flow in circular reactors.

Measurement and prediction of mass transfer coefficients for syngas constituents in a hollow fiber reactor.

Syngas fermentation for producing biofuels and other products suffers from mass transfer limitations due to low CO and H2 solubility in liquid medium. Therefore, it is critical to characterize mass transfer rates of these gases to guide bioreactor design and optimization. This work presents a novel technique to measure the volumetric mass transfer coefficients (kia) for H2 and CO using gas chromatography in a non-porous hollow fiber reactor (HFR). The largest measured kia for H2 and CO were 840 and 420 h-1, respectively. A model was developed to predict kia for H2 and CO that agreed well with experimental data. This study is the first to measure, compare, and model both H2 and CO mass transfer coefficients in an HFR. Based on model predictions, HFRs have the potential to be a reactor of choice for syngas fermentation as a result of high mass transfer that can support high cell densities.

Ethanol production during semi-continuous syngas fermentation in a trickle bed reactor using Clostridium ragsdalei.

An efficient syngas fermentation bioreactor provides a mass transfer capability that matches the intrinsic kinetics of the microorganism to obtain high gas conversion efficiency and productivity. In this study, mass transfer and gas utilization efficiencies of a trickle bed reactor during syngas fermentation by Clostridium ragsdalei were evaluated at various gas and liquid flow rates. Fermentations were performed using a syngas mixture of 38% CO, 28.5% CO2, 28.5% H2 and 5% N2, by volume. Results showed that increasing the gas flow rate from 2.3 to 4.6sccm increased the CO uptake rate by 76% and decreased the H2 uptake rate by 51% up to Run R6. Biofilm formation after R6 increased cells activity with over threefold increase in H2 uptake rate. At 1662h, the final ethanol and acetic acid concentrations were 5.7 and 12.3g/L, respectively, at 200ml/min of liquid flow rate and 4.6sccm gas flow rate.

A comparison of mass transfer coefficients between trickle-bed, hollow fiber membrane and stirred tank reactors.

Trickle-bed reactor (TBR), hollow fiber membrane reactor (HFR) and stirred tank reactor (STR) can be used in fermentation of sparingly soluble gasses such as CO and H2 to produce biofuels and bio-based chemicals. Gas fermenting reactors must provide high mass transfer capabilities that match the kinetic requirements of the microorganisms used. The present study compared the volumetric mass transfer coefficient (K(tot)A/V(L)) of three reactor types; the TBR with 3 mm and 6 mm beads, five different modules of HFRs, and the STR. The analysis was performed using O2 as the gaseous mass transfer agent. The non-porous polydimethylsiloxane (PDMS) HFR provided the highest K(tot)A/V(L) (1062 h(-1)), followed by the TBR with 6mm beads (421 h(-1)), and then the STR (114 h(-1)). The mass transfer characteristics in each reactor were affected by agitation speed, and gas and liquid flow rates. Furthermore, issues regarding the comparison of mass transfer coefficients are discussed.