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Biomedical subjects

Francesco Migliavacca

Publications and source records attributed to Francesco Migliavacca.

At least 19 recordsLinked to original sources

Prediction of the micro-fluid dynamic environment imposed to three-dimensional engineered cell systems in bioreactors.

Bioreactors allowing culture medium perfusion overcome diffusion limitations associated with static culturing and provide flow-mediated mechanical stimuli. The hydrodynamic stress imposed to cells will depend not only on the culture medium flow rate, but also on the scaffold three-dimensional (3D) micro-architecture. We developed a CFD model of the flow of culture medium through a 3D scaffold of homogeneous geometry, with the aim of predicting the shear stress acting on cells as a function of parameters that can be controlled during the scaffold fabrication process, such as the scaffold porosity and the pore size, and during the cell culture, such as the medium flow rate and the diameter of the perfused scaffold section. We built three groups of models corresponding to three pore sizes: 50, 100 and 150 microm. Each group was made of four models corresponding to 59%, 65%, 77%, and 89% porosity. A commercial finite-element code was used to set up and solve the problem and to analyze the results. The mode value of shear stress varied between 2 and 5 mPa, and was obtained for a circular scaffold of 15.5 mm diameter, perfused by a flow rate of 0.5 ml/min. The simulations showed that the pore size is a variable strongly influencing the predicted shear stress level, whereas the porosity is a variable strongly affecting the statistical distribution of the shear stresses, but not their magnitude. Our results provide a basis for the completion of more exhaustive quantitative studies to further assess the relationship between perfusion, at known micro-fluid dynamic conditions, and tissue growth in vitro.

Bioreactors↗

Multiscale modelling in biofluidynamics: application to reconstructive paediatric cardiac surgery.

Multiscale computing is a challenging area even in biomechanics. Application of such a methodology to quantitatively compare postoperative hemodynamics in congenital heart diseases is very promising. In the treatment of hypoplastic left heart syndrome, which is a congenital heart disease where the left ventricle is missing or very small, the necessity to feed the pulmonary and systemic circulations is obtained with an interposition shunt. Two main options are available and differ from the sites of anastomoses: (i) the systemic-to-pulmonary conduit (Blalock-Taussig shunt known as the Norwood Operation (NO)) connecting the innominate artery (NO-BT) or the aorta (NO-CS) to the right pulmonary artery and (ii) the right ventricle to pulmonary artery shunt (known as Sano operation (SO)). The proposition that the SO is superior to the NO remains controversial. 3-D computer models of the NO (NO-BT and NO-CS) and SO were developed and investigated using the finite volume method. Conduits of 3, 3.5 and 4 mm were used in the NO models, whereas conduits of 4, 5 and 6 mm were used in the SO model. The hydraulic nets (lumped resistances, compliances, inertances and elastances) which represent the systemic, coronary and pulmonary circulations and the heart were identical in the two models. A multiscale approach was adopted to couple the 3-D models with the circulation net. Computer simulation results were compared with post-operative catheterization data. Results showed that (i) there is a good correlation between predicted and observed data: higher aortic diastolic pressure, decreased pulmonary arterial pressure, lower pulmonary-to-systemic flow ratio and higher coronary perfusion pressure in SO; (ii) there is a minimal regurgitant flow in the SO conduit. The close correlation between predicted and observed clinical data supports the use of mathematical modelling, with a mandatory multiscale approach, in the design and assessment of surgical procedures.

Algorithms↗

Computational modeling of vascular anastomoses.

Recent development of computational technology allows a level of knowledge of biomechanical factors in the healthy or pathological cardiovascular system that was unthinkable a few years ago. In particular, computational fluid dynamics (CFD) and computational structural (CS) analyses have been used to evaluate specific quantities, such as fluid and wall stresses and strains, which are very difficult to measure in vivo. Indeed, CFD and CS offer much more variability and resolution than in vitro and in vivo methods, yet computations must be validated by careful comparison with experimental and clinical data. The enormous parallel development of clinical imaging such as magnetic resonance or computed tomography opens a new way toward a detailed patient-specific description of the actual hemodynamics and structural behavior of living tissues. Coupling of CFD/CS and clinical images is becoming a standard evaluation that is expected to become part of the clinical practice in the diagnosis and in the surgical planning in advanced medical centers. This review focuses on computational studies of fluid and structural dynamics of a number of vascular anastomoses: the coronary bypass graft anastomoses, the arterial peripheral anastomoses, the arterio-venous graft anastomoses and the vascular anastomoses performed in the correction of congenital heart diseases.

Anastomosis, Surgical↗

Multiscale modeling of the cardiovascular system: application to the study of pulmonary and coronary perfusions in the univentricular circulation.

The objective of this study is to compare the coronary and pulmonary blood flow dynamics resulting from two configurations of systemic-to-pulmonary artery shunts currently utilized during the Norwood procedure: the central (CS) and modified Blalock Taussig (MBTS) shunts. A lumped parameter model of the neonatal cardiovascular circulation and detailed 3-D models of the shunt based on the finite volume method were constructed. Shunt sizes of 3, 3.5 and 4 mm were considered. A multiscale approach was adopted to prescribe appropriate and realistic boundary conditions for the 3-D models of the Norwood circulation. Results showed that the average shunt flow rate is higher for the CS option than for the MBTS and that pulmonary flow increases with shunt size for both options. Cardiac output is higher for the CS option for all shunt sizes. Flow distribution between the left and the right pulmonary arteries is not completely balanced, although for the CS option the discrepancy is low (50-51% of the pulmonary flow to the right lung) while for the MBTS it is more pronounced with larger shunt sizes (51-54% to the left lung). The CS option favors perfusion to the right lung while the MBTS favors the left. In the CS option, a smaller percentage of aortic flow is distributed to the coronary circulation, while that percentage rises for the MBTS. These findings may have important implications for coronary blood flow and ventricular function.

Blood Flow Velocity↗

A predictive study of the mechanical behaviour of coronary stents by computer modelling.

Intravascular stents are small tube-like structures expanded into stenotic arteries to restore blood flow perfusion to the downstream tissues. The stent expansion is an important factor to define the effectiveness of the surgical procedure: it depends on the stent geometry and includes large displacements and deformations, geometric and material non-linearity. Numerical analyses seem appropriate to study such a complex behaviour after a free stent expansion. In this study the finite element method (FEM) was applied to a new generation coronary stent. Results from computations were compared with those from a laboratory experiment in terms of radial expansion and elastic recoil. By means of a scanning electronic microscopy the area of plastic deformation were also detected and compared with those obtained in the numerical simulation. Matching between the different measurements was quite satisfactory even if some discrepancies were present due to the absence of the balloon in the numerical model.

Angioplasty, Balloon, Coronary↗

Computational studies of shape memory alloy behavior in biomedical applications.

BACKGROUND: Nowadays, shape memory alloys (SMAs) and in particular Ni-Ti alloys are commonly used in bioengineering applications as they join important qualities as resistance to corrosion, biocompatibility, fatigue resistance, MR compatibility, kink resistance with two unique thermo-mechanical behaviors: the shape memory effect and the pseudoelastic effect. They allow Ni-Ti devices to undergo large mechanically induced deformations and then to recover the original shape by thermal loading or simply by mechanical unloading. METHOD OF APPROACH: A numerical model is developed to catch the most significant SMA macroscopic thermo-mechanical properties and is implemented into a commercial finite element code to simulate the behavior of biomedical devices. RESULTS: The comparison between experimental and numerical response of an intravascular coronary stent allows to verify the model suitability to describe pseudo-elasticity. The numerical study of a spinal vertebrae spacer where the effects of different geometries and material characteristic temperatures are investigated, allows to verify the model suitability to describe shape memory effect. CONCLUSION: the results presented show the importance of computational studies in designing and optimizing new biomedical devices.

Alloys↗

On the use of computational models for the quantitative assessment of surgery in congenital heart disease.

The surgical repair of congenital heart disease often involves significant modifications to the circulatory tree. Resections, reconstructions, graft insertions and the deployment of implants and biomedical devices have an impact on local and systemic haemodynamics, which may be difficult to foresee or to assess quantitatively by clinical investigation alone. Mathematical models can be employed to visualise, estimate or predict events and physical quantities that are difficult to observe or measure, and can be successfully applied to the study of the pre- and post-operative physiology of cardiovascular malformations. This paper analyses the potentialities of computation fluid dynamics in this respect, outlining the method, its requirements and its limitations. Examples are given of lumped parameter models, axi-symmetric models, three-dimensional models, fluid-structure interaction simulations and multiscale computing applied to total cavo-pulmonary connection, aortic coarctation and aortic arch reconstruction.

Cardiovascular Surgical Procedures↗

Stainless and shape memory alloy coronary stents: a computational study on the interaction with the vascular wall.

Balloon-expandable and self-expandable stents are the two types of coronary stents available. Basically, they differ in the modality of expansion. The present study analyses the stress state induced on the vascular wall, by the expansion of balloon- and self-expandable stents, using the finite element method. Indeed, modified mechanical stress state is in part responsible in the restenosis process. The balloon-expandable stents herein investigated are assumed to be made of stainless steel, while the self-expandable stents are made of a shape memory alloy. The effects of the severity of the coronary stenosis, the atherosclerotic plaque stiffness and the stent design are investigated. Comparing the self-expandable stent with the balloon-expandable one, the former induces fewer stresses and lower damage to the vessel, but, on the other hand, its lower stiffness induces a lower capability to restore vasal lumen and to contrast arterial elastic recoil.

Alloys↗

Numerical investigation of the intravascular coronary stent flexibility.

Nowadays stent therapy is widely adopted to treat atherosclerotic vessel diseases. The high commercial value of these devices and the high prototypation costs require the use of finite element analyses, instead of classical trial and error technique, to design and verify new models. In this paper, we explore the advantages of the finite element method (FEM) in order to investigate new generation stent performance in terms of flexibility. Indeed, the ability of the stent to bend in order to accommodate curvatures and angles of vessels during delivery is one of the most significant prerequisites for optimal stent performance. Two different FEM models, resembling two new generation intravascular stents, were developed. The main model dimensions were obtained by means of a stereo microscope, analyzing one Cordis BX-Velocity and one Carbostent Sirius coronary stent. Bending tests under displacement control in the unexpanded and expanded configuration were carried out. The curvature index, defined as the ratio between the sum of rotation angles at the extremes and the length of the stent, yielded comparative information about the capability of the device to be delivered into tortuous vessels and to conform to their contours. Results, expressed in terms of the bending moment-curvature index, demonstrated a different response for the two models. In particular the Cordis model showed a higher flexibility. Lower flexibility in the expanded configurations for both models was detected. However this flexibility depends on how the contact takes place between the different parts of the struts.

Coronary Vessels↗

Computational fluid dynamic study of flow optimization in realistic models of the total cavopulmonary connections.

OBJECTIVES AND BACKGROUND: In the Fontan circulation, pulmonary and systemic vascular resistances are in series. The influence of various inferior vena cava to pulmonary artery connections in this unique circulatory arrangement was evaluated using computation fluid dynamics methods. METHODS: Realistic three-dimensional models of total cavopulmonary connections were created from angiographic measurements to include the hepatic vein, superior vena cava, and branches of the pulmonary arteries. Steady-state finite volume analyses were performed using identical in vivo boundary conditions. Computational solutions calculated the percent hydraulic power dissipation and left-to-right pulmonary arterial flow distribution. RESULTS: Simulations of the lateral tunnel, intra-atrial tube, extracardiac conduit with left and right pulmonary artery anastomosis demonstrated extracardiac conduit with left pulmonary artery anastomosis having the lowest energy loss. Varying the extracardiac conduit from 10 to 30 mm resulted in the least energy dissipation at 20 mm. Serial dilation of the lateral tunnel pathway showed a small incremental worsening of energy loss. CONCLUSIONS: Maximizing energy conservation in a low-energy flow domain, such as the Fontan circulation, can be significant to its fluid dynamic performance. Although computational modeling cannot predict postoperative failure or functional outcome, this study confirms the importance of local geometry of the surgically created pathway in the total cavopulmonary connection.

Blood Vessel Prosthesis↗

Contact stresses and fatigue life in a knee prosthesis: comparison between in vitro measurements and computational simulations.

The evaluation of contact areas and pressures in total knee prosthesis is a key issue to prevent early failure. The first part of this study is based on the hypothesis that the patterns of contact stresses on the tibial insert of a knee prosthesis at different stages of the gait cycle could be an indicator of the wear performances of a knee prosthesis. Contact stresses were calculated for a mobile bearing knee prosthesis by means of finite element method (FEM). Contact areas and stresses were also measured through in vitro tests using Fuji Prescale film in order to support the FEM findings. The second part of this study addresses the long-term structural integrity of metal tibial components in terms of fatigue life by means of experimental tests and FEM simulations. Fatigue experimental evaluations were performed on Cr-Co alloy tibial tray, based on ISO standards. FEM models were used to calculate the stress patterns. The failure risk was estimated with a standard fatigue criterion on the basis of the results obtained from the FEM calculations. Experimental and computational results showed a positive matching.

Computer Simulation↗

The effect of media perfusion on three-dimensional cultures of human chondrocytes: integration of experimental and computational approaches.

This work examines the effect of perfusion on human mature articular chondrocytes cultured on synthetic biodegradable scaffolds (DegraPol). Human chondrocytes were isolated, seeded on the scaffolds and subjected to perfused culture at a flow rate of 0.5 ml/min, corresponding to an average inlet fluid velocity of 44 microm/s, with flow inversion every 1 minute. The flow was imposed at the construct surface in some constructs, it was forced through the construct thickness in other constructs and was absent in the static controls. We compared cell viability and morphology and we evaluated material properties of the constructs at 1 month of culture. Thickness-perfused constructs showed significantly higher material properties and roughly a two-fold cell viability, when compared both to surface-perfused constructs and to static controls. Chondrocytes maintained a phenotypic morphology in all experiments, probably favoured by a limited cell-scaffold interaction. Biosynthetic activity could be demonstrated only in the bioreactor-cultured constructs. In this experimental model, a bi-directional flow of culture medium was applied to the cells at a macroscopic level and computational modelling was used to quantify the fluid-dynamic environment induced on the cells at a microscopic level. This method may be used to quantify the effects of fluid-dynamic shear on the growth modulation of tissue-engineered cartilage constructs, to potentially enhance tissue growth in vitro.

Biomechanical Phenomena↗