Mcm Marcel Rutten

Electrospinning versus knitting: two scaffolds for tissue engineering of the aortic valve

Two types of scaffolds were developed for tissue engineering of the aortic valve; an electrospun valvular scaffold and a knitted valvular scaffold. These scaffolds were compared in a physiologic flow system and in a tissue-engineering process. In fibrin gel enclosed human myofibroblasts were seeded onto both types of scaffolds and cultured for 23 days under continuous medium perfusion. Tissue formation was evaluated by confocal laser scanning microscopy, histology and DNA quantification. Collagen formation was quantified by a hydroxyproline assay. When subjected to physiologic flow, the spun scaffold tore within 6 h, whereas the knitted scaffold remained intact. Cells proliferated well on both types of scaffolds, although the cellular penetration into the spun scaffold was poor. Collagen production, normalized to DNA content, was not significantly different for the two types of scaffolds, but seeding efficiency was higher for the spun scaffold, because it acted as a cell impermeable filter. The knitted tissue constructs showed complete cellular in-growth into the pores. An optimal scaffold seems to be a combination of the strength of the knitted structure and the cell-filtering ability of the spun structure.

A wave propagation model of blood flow in large vessels using an approximate velocity profile function

Lumped-parameter models (zero-dimensional) and wave-propagation models (one-dimensional) for pressure and flow in large vessels, as well as fully three-dimensional fluid–structure interaction models for pressure and velocity, can contribute valuably to answering physiological and patho-physiological questions that arise in the diagnostics and treatment of cardiovascular diseases. Lumped-parameter models are of importance mainly for the modelling of the complete cardiovascular system but provide little detail on local pressure and flow wave phenomena. Fully three-dimensional fluid–structure interaction models consume a large amount of computer time and must be provided with suitable boundary conditions that are often not known. One-dimensional wave-propagation models in the frequency and time domain are well suited to obtaining clinically relevant information on local pressure and flow waves travelling through the arterial system. They can also be used to provide boundary conditions for fully three-dimensional models, provided that they are defined in, or transferred to, the time domain. Most of the one-dimensional wave propagation models in the time domain described in the literature assume velocity profiles and therefore frictional forces to be in phase with the flow, whereas from exact solutions in the frequency domain a phase difference between the flow and the wall shear stress is known to exist. In this study an approximate velocity profile function more suitable for one-dimensional wave propagation is introduced and evaluated. It will be shown that this profile function provides first-order approximations for the wall shear stress and the nonlinear term in the momentum equation, as a function of local flow and pressure gradient in the time domain. The convective term as well as the approximate friction term are compared to their counterparts obtained from Womersley profiles and show good agreement in the complete range of the Womersley parameter α. In the limiting cases, for Womersley parameters α → 0 and α → ∞, they completely coincide. It is shown that in one-dimensional wave propagation, the friction term based on the newly introduced approximate profile function is important when considering pressure and flow wave propagation in intermediate-sized vessels.

Dynamic Straining Combined with Fibrin Gel Cell Seeding Improves Strength of Tissue-Engineered Small-Diameter Vascular Grafts

Vascular tissue engineering represents a promising approach for the development of living small-diameter vascular grafts that can be used for replacement therapy. The culture of strong human tissue-engineered (TE) vascular grafts has required long culture times, up to several months, whether or not combined with gene therapy. This article describes the culture of strong, genetically unmodified, human TE vascular grafts in 4 weeks Small-diameter vascular grafts were engineered using a fast-degrading polyglycolic acid scaffold coated with poly-4-hydroxybutyrate combined with fibrin gel and seeded with myofibroblasts isolated from discarded saphenous veins from patients undergoing coronary bypass surgery. The TE grafts were subjected to dynamic strain conditions. After 28 d of in vitro culture, the grafts demonstrated burst pressures of 903 +/- 123 mmHg. Comparison with native vessels (intact human left internal mammary arteries (LIMAs) and saphenous veins) showed no significant differences in the amount of DNA, whereas the TE vessels contained approximately 50% of the native collagen content. In the physiological pressure range, up to 300 mmHg, the mechanical properties of the TE vessels were comparable to the LIMA. In this study, we showed that dynamic conditioning combined with fibrin gel cell seeding enhances the mechanical properties of small-diameter TE grafts. These grafts might provide a promising alternative to currently used vascular replacements.

A physiologically representative in vitro model of the coronary circulation

With the development of clinical diagnostic techniques to investigate the coronary circulation in conscious humans, the in vitro validation of such newly developed techniques is of major importance. The aim of this study was to develop an in vitro model that is able to mimic the coronary circulation in such a way that coronary pressure and flow signals under baseline as well as hyperaemic conditions are approximated as realistically as possible and are in accordance with recently gained insights into such signals in conscious man. In the present in vitro model the heart, the systemic and coronary circulation are modelled on the basis of the elements of a lumped parameter mathematical model only consisting of elements that can be represented by segments in an experimental set-up. A collapsible tube, collapsed by the ventricular pressure, represents the variable resistance and volume behaviour of the endocardial part of the myocardium. The pressure and flow signals obtained are similar to physiological human coronary pressure and flow, both for baseline and hyperaemic conditions. The model allows for in vitro evaluation of clinical diagnostic techniques.

A mathematical model to evaluate control strategies for mechanical circulatory support

Continuous flow ventricular assist devices (VADs) for mechanical circulatory support (MCS) are generally smaller and believed to be more reliable than pulsatile VADs. However, regarding continuous flow, there are concerns about the decreased pulsatility and ventricular unloading. Moreover, pulsatile VADs offer a wider range in control strategies. For this reason, we used a computer model to evaluate whether pulsatile operation of a continuous flow VAD would be more beneficial than the standard constant pump speed. The computer model describes the left and right ventricle with one-fiber heart contraction models, and the systemic, pulmonary, and coronary circulation with lumped parameter hemodynamical models, while the heart rate is regulated with a baroreflex model. With this computer model, both normal and heart failure hemodynamics were simulated. A HeartMate II left ventricular assist device model was connected to this model, and both constant speed and pulsatile support were simulated. Pulsatile support did not solve the decreased pulsatility issue, but it did improve perfusion (cardiac index and coronary flow) and unloading (stroke work and heart rate) compared with constant speed. Also, pulsatile support would be beneficial for developing control strategies, as it offers more options to adjust assist device settings to the patients needs. Because the mathematical model used in this study can simulate different assist device settings, it can play a valuable role in developing mechanical circulatory support control strategies.

Non-linear viscoelastic behavior of abdominal aortic aneurysm thrombus

The objective of this work was to determine the linear and non-linear viscoelastic behavior of abdominal aortic aneurysm thrombus and to study the changes in mechanical properties throughout the thickness of the thrombus. Samples are gathered from thrombi of seven patients. Linear viscoelastic data from oscillatory shear experiments show that the change of properties throughout the thrombus is different for each thrombus. Furthermore the variations found within one thrombus are of the same order of magnitude as the variation between patients. To study the non-linear regime, stress relaxation experiments are performed. To describe the phenomena observed experimentally, a non-linear multimode model is presented. The parameters for this model are obtained by fitting this model successfully to the experiments. The model cannot only describe the average stress response for all thrombus samples but also the highest and lowest stress responses. To determine the influence on the wall stress of the behavior observed the model proposed needs to implemented in the finite element wall stress analysis.

Complex flow patterns in a real-size intracranial aneurysm phantom: phase contrast MRI compared with particle image velocimetry and computational fluid dynamics

The aim of this study was to validate the flow patterns measured by high‐resolution, time‐resolved, three‐dimensional phase contrast MRI in a real‐size intracranial aneurysm phantom. Retrospectively gated three‐dimensional phase contrast MRI was performed in an intracranial aneurysm phantom at a resolution of 0.2 × 0.2 × 0.3 mm3 in a solenoid rat coil. Both steady and pulsatile flows were applied. The phase contrast MRI measurements were compared with particle image velocimetry measurements and computational fluid dynamics simulations. A quantitative comparison was performed by calculating the differences between the magnitude of the velocity vectors and angles between the velocity vectors in corresponding voxels. Qualitative analysis of the results was executed by visual inspection and comparison of the flow patterns. The root‐mean‐square errors of the velocity magnitude in the comparison between phase contrast MRI and computational fluid dynamics were 5% and 4% of the maximum phase contrast MRI velocity, and the medians of the angle distribution between corresponding velocity vectors were 16° and 14° for the steady and pulsatile measurements, respectively. In the phase contrast MRI and particle image velocimetry comparison, the root‐mean‐square errors were 12% and 10% of the maximum phase contrast MRI velocity, and the medians of the angle distribution between corresponding velocity vectors were 19° and 15° for the steady and pulsatile measurements, respectively. Good agreement was found in the qualitative comparison of flow patterns between the phase contrast MRI measurements and both particle image velocimetry measurements and computational fluid dynamics simulations. High‐resolution, time‐resolved, three‐dimensional phase contrast MRI can accurately measure complex flow patterns in an intracranial aneurysm phantom. Copyright

A NONINVASIVE METHOD TO ESTIMATE ARTERIAL IMPEDANCE BY MEANS OF ASSESSMENT OF LOCAL DIAMETER CHANGE AND THE LOCAL CENTER-LINE BLOOD FLOW VELOCITY USING ULTRASOUND

Vascular impedance is defined as the ratio between the frequency components of the local blood pressure waveform and those of the local blood volume flow waveform. Assessment of vascular impedance is, for example, important to study heart load and distal vascular bed vasomotricity. However, only a few studies on vascular impedance have been performed in humans because pulsatile pressure and volume flow waveforms, simultaneously recorded at the same location, are difficult to obtain noninvasively. The noninvasive assessment of arterial impedance as described in this study is based on the replacement of the pressure waveform by the distension (change in diameter) waveform and the volume flow waveform by the center-line blood flow velocity waveform. Both waveforms can simultaneously and accurately be assessed by means of pulsed ultrasound. It will be shown that, depending on the Womersley number, the volume flow waveform may be replaced by the center-line blood flow velocity waveform for a given frequency range and that the pressure waveform may be replaced by the distension waveform for a wide frequency range. The validation of the proposed ultrasound method was performed through an in vitro study in a flow model with a distensible tube terminated with a hydraulic load (modified windkessel model). It is shown that, in vitro, the proposed method gives the same results as the local spectral pressure-flow relationship.

Toward Noninvasive Blood Pressure Assessment in Arteries by Using Ultrasound

A new method has been developed to measure local pressure waveforms in large arteries by using ultrasound. The method is based on a simultaneous estimation of distension waveforms and velocity profiles from a single noninvasive perpendicular ultrasound B-mode measurement. Velocity vectors were measured by applying a cross-correlation based technique to ultrasound radio-frequency (RF) data. From the ratio between changes in flow and changes in cross-sectional area of the vessel, the local pulse wave velocity (PWV) was estimated. This PWV value was used to convert the distension waveforms into pressure waveforms. The method was validated in a phantom set-up. Physiologically relevant pulsating flows were considered, employing a fluid which mimics both the acoustic and rheologic properties of blood. A linear array probe attached to a commercially available ultrasound scanner was positioned parallel to the vessel wall. Since no steering was used, the beam was perpendicular to the flow. The noninvasively estimated pressure waveforms showed a good agreement with the reference pressure waveforms. Pressure values were predicted with a precision of 0.2 kPa (1.5 mm Hg). An accurate beat to beat pressure estimation could be obtained, indicating that a noninvasive pressure assessment in large arteries by means of ultrasound is feasible.

Real Time, Non-Invasive Assessment of Leaflet Deformation in Heart Valve Tissue Engineering

In heart valve tissue engineering, most bioreactors try to mimic physiological flow and operate with a preset transvalvular pressure applied to the tissue. The induced deformations are unknown and can vary during culturing as a consequence of changing mechanical properties of the engineered construct. Real-time measurement and control of local tissue strains are desired to systematically study the effects of mechanical loading on tissue development and, consequently, to design an optimal conditioning protocol. In this study, a method is presented to assess local tissue strains in heart valve leaflets during culturing. We hypothesize that local tissue strains can be determined from volumetric deformation. Volumetric deformation is defined as the amount of fluid displaced by the deformed heart valve leaflets in a stented configuration, and is measured, non-invasively, using a flow sensor. A numerical model is employed to relate volumetric deformation to local tissue strains in various regions of the leaflets (e.g. belly and commissures). The flow-based deformation measurement method was validated and its functionality was demonstrated in a tissue engineering experiment. Tri-leaflet, stented heart valves were cultured in vitro and during mechanical conditioning, realistic values for volumetric and local deformation were obtained.