Tissue engineered heart valves (TEHV) have been observed to respond to mechanical conditioning in vitro by expression of activated myofibroblast phenotypes followed by improvements in tissue maturation. In separate studies, cyclic flexure, stretch, and flow (FSF) have been demonstrated to exhibit both independent and coupled stimulatory effects. Synthesis of these observations into a rational framework for TEHV mechanical conditioning has been limited, however, due to the functional complexity of trileaflet valves and the inherent differences of separate bioreactor systems. Toward quantifying the effects of individual mechanical stimuli similar to those that occur during normal valve function, a novel bioreactor was developed in which FSF mechanical stimuli can be applied to engineered heart valve tissues independently or in combination. The FSF bioreactor consists of two identically equipped chambers, each having the capacity to hold up to 12 rectangular tissue specimens (25 × 7.5 × 1 mm) via a novel "spiralbound" technique. Specimens can be subjected to changes-in-curvature up to 50 mm −1 and uniaxial tensile strains up to 75%. Steady laminar flow can be applied by a magnetically coupled paddlewheel system. Computational fluid dynamic (CFD) simulations were conducted and experimentally validated by particle image velocimetry (PIV). Tissue specimen wall shear stress profiles were predicted as a function of paddlewheel speed, culture medium viscosity, and the quasi-static state of specimen deformation (i.e., either undeformed or completely flexed). Velocity profiles predicted by 2D CFD simulations of the paddlewheel mechanism compared well with PIV measurements, and were used to determine boundary conditions in localized 3D simulations. For undeformed specimens, predicted inter-specimen variations in wall shear stress were on average ±7%, with an average wall shear stress of 1.145 dyne/cm 2 predicted at a paddlewheel speed of 2000 rpm and standard culture conditions. In contrast, while the average wall shear stress predicted for specimens in the quasi-static flexed state was ~59% higher (1.821 dyne/cm 2 ), flexed specimens exhibited a broad intra-specimen wall shear stress distribution between the convex and concave sides that correlated with specimen curvature, with peak wall shear stresses of ~10 dyne/ cm 2 . This result suggests that by utilizing simple flexed geometric configurations, the present system can also be used to study the effects of spatially varying shear stresses. We conclude that the present design provides a robust tool for the study of mechanical stimuli on in vitro engineered heart valve tissue formation.
We are developing an intravenous respiratory assist catheter, which uses hollow-fiber membranes wrapped around a pulsating balloon that increases oxygenation and CO2 removal with increased balloon pulsation. Our current pulsation system operates with a constant rate of pulsation and delivered balloon volume. This study examined the hypothesis that random balloon pulsation would disrupt fluid entrainment within the fiber bundle and increase our overall gas exchange. We implemented two different modes for random (rates and delivered volume) versus constant pulsation. The impact on gas exchange was measured in a 3 l/min water flow loop at 37 degrees C. CO2 gas exchange for randomized beat rate mode was comparable to its corresponding average constant pulsation (e.g., constant 286 beats/min versus randomized 200-400 beats/min was 299.5+/-0.9 and 302.2+/-1.4 ml/min/m, respectively). Random volume mode CO2 exchange was also comparable to constant delivered balloon volume (100% inflation and deflation) (e.g., 294.3+/-0.6 and 301.1+/-1.7 ml/min/m, random 50-100% inflation and constant, respectively). Greater active mixing was seen with constant pulsation as compared with randomly changing the parameters of balloon pulsation.
Our group is currently developing an intravenous respiratory assist device that uses a centrally located pulsatile balloon within a hollow fiber bundle to enhance gas exchange rate via active mixing mechanism. We tested the hypothesis that the nonsymmetric inflation and deflation of the balloon lead to both nonuniform balloon-generated secondary flow and nonuniform gas exchange rate in the fiber bundle. The respiratory catheter was placed in a 1-in. internal diameter rigid test section of an in vitro flow loop (3 L/min deionized water). Particle image velocimetry (PIV), which was used to map the velocity vector field in the lateral cross-section, showed that the balloon pulsation generated a nonuniform fluid flow surrounding the respiratory assist catheter. PIV was also used to characterize the fiber bundle movement, which was induced by the balloon pulsation. Gas permeability coefficient of the device was evaluated by using both the fluid velocity and the relative velocity between the fluid and the fiber bundle. The highest difference in the gas permeability coefficient predicted by using the relative velocity was about 17% to 23% (angular direction), which was more uniform than the 49% to 59% variation predicted by using the fluid velocity. The movement of the fiber bundle was responsible for reducing the variation in the fluid velocity passing through the bundle and for minimizing the nonuniformity of the gas permeability coefficient of the respiratory assist catheter.Our group has been actively developing the intravenous respiratory assist catheter based on hollow fiber membrane technology to provide a temporary support for patients with acute or acute-on-chronic respiratory failure such as, acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD).1 -3 The respiratory assist catheter consists of a constrained hollow fiber membrane bundle wrapped around a pulsating balloon. It is placed within the vena cava via the femoral vein insertion to supply oxygen and to remove carbon dioxide before the blood reaches the natural lung. As a result, the use of the respiratory assist catheter allows the lung to rest and heal, which is a benefit over mechanical ventilation. Respiratory support with this device may also potentially be less expensive and simpler than that with the extracorporeal membrane oxygenation (ECMO), because ECMO requires labor-intensive patient monitoring and increased blood or biomaterial contact in extracorporeal circuits. Copyright Our previous study with an ex vivo flow loop4 and acute animal testing5 confirmed that a rapid pulsation of the centrally placed balloon was capable of enhancing the O 2 and CO 2 transfer rates greater than the nonpulsating device such as IVOX (intravenous oxygenator). 6 -9 The enhancement in gas exchange primarily results from the generation of convective blood flow perpendicular to the fiber1 by the inflation and deflation of the balloon. Wickramasinghe et al.10 have looked at the oxygen exchange rate in hollow fiber membra...
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