Mehmet H. Kural

Planar biaxial characterization of diseased human coronary and carotid arteries for computational modeling

Computational models have the potential to provide precise estimates of stresses and strains associated with sites of coronary plaque rupture. However, lack of adequate mathematical description of diseased human vessel wall mechanical properties is hindering computational accuracy. The goal of this study is to characterize the behavior of diseased human coronary and carotid arteries using planar biaxial testing. Diseased coronary specimens exhibit relatively high stiffness (50-210 kPa) and low extensibility (1-10%) at maximum equibiaxial stress (250 kPa) compared to human carotid specimens and values commonly reported for porcine coronary arteries. A thick neointimal layer observed histologically appears to be associated with heightened stiffness and the direction of anisotropy of the specimens. Fung, Choi-Vito and modified Mooney-Rivlin constitutive equations fit the multiaxial data from multiple stress protocols well, and parameters from representative coronary specimens were utilized in a finite element model with fluid-solid interactions. Computed locations of maximal stress and strain are substantially altered, and magnitudes of maximum principal stress (48-65 kPa) and strain (6.5-8%) in the vessel wall are lower than previously predicted using parameters from uniaxial tests. Taken together, the results demonstrate the importance of utilizing disease-matched multiaxial constitutive relationships within patient-specific computational models to accurately predict stress and strain within diseased coronary arteries.

Regulating tension in three-dimensional culture environments

The processes of development, repair, and remodeling of virtually all tissues and organs, are dependent upon mechanical signals including external loading, cell-generated tension, and tissue stiffness. Over the past few decades, much has been learned about mechanotransduction pathways in specialized two-dimensional culture systems; however, it has also become clear that cells behave very differently in two- and three-dimensional (3D) environments. Three-dimensional in vitro models bring the ability to simulate the in vivo matrix environment and the complexity of cell-matrix interactions together. In this review, we describe the role of tension in regulating cell behavior in three-dimensional collagen and fibrin matrices with a focus on the effective use of global boundary conditions to modulate the tension generated by populations of cells acting in concert. The ability to control and measure the tension in these 3D culture systems has the potential to increase our understanding of mechanobiology and facilitate development of new ways to treat diseased tissues and to direct cell fate in regenerative medicine and tissue engineering applications.

Planar Biaxial Characterization of Human Coronary and Carotid Arteries for Computational Modeling

Finite element analyses (FEA) provide contributions to clinical cardiovascular applications such as assessment of plaque vulnerability, the mechanical optimization of balloon angioplasty and stent deployment. However, FEA-predicted stresses for physiological and pathological states are dependent heavily on the accuracy of material models utilized. Thus, developing accurate quantitative descriptions for the multiaxial mechanical behavior of blood vessels is essential for developing accurate computational models for arterial stiffness.Copyright

A device for dynamic modulation of cell-generated tension in 3D biopolymer gels

The mechanical environment surrounding cells has a critical impact on their behavior, including differentiation, migration, shape and proliferation. Studies have shown that substrate stiffness plays a key role in the behavior of cells grown on 2D substrates, and substrates with dynamic modulus. However, methods for studying cellular response to active changes in stiffness in 3D are lacking. The goal of this project was to develop a method to mechanically modulate the boundary stiffness experienced by fibroblasts in a 3D gel to mimic extracellular matrix. We created a device that utilizes thin stainless steel cantilevered beams that support cell-seeded gels suspended within a culture well. The boundary stiffness is dynamically modulated by a clamp which changes the active length of the cantilever beams. The tensile forces generated by the cells can be quantified based on the calculated spring constant for the active length of the particular set of beams and the subsequent deflection of the beams from cellular contraction of the collagen gel. Spring constants at various clamp heights were validated using force vs. displacement testing of the prototype. In future experiments, collagen gels populated with cells will be grown around the end of the beams, tension will be quantified based on deflection, and active length will be actuated to observe changes in gel contraction, cell proliferation and differentiation. This device has the potential to add significantly to our knowledge of how cells respond to changes in their mechanical environment.

3D Computational Fluid-Structure Interaction Model of Canine Heart With Different Patch Materials for Optimal Myocardium Regeneration

Myocardial tissue regeneration techniques are being developed for the potential that viable myocardium may be regenerated to replace scar tissues in the heart or used as patch material in heart surgery [1]. The material property of the patch on which myocardium cells are placed has important impact on cell adhesion and multiplication [2]. Fluid-structure interaction (FSI) models for canine heart with patch was introduced to quantify regional flow and mechanical conditions in the patch area and investigate the influence of the different patch materials on myocardium regeneration.© 2013 ASME

Effect of Boundary Stiffness on Contractility Profile of Valvular Interstitial Cells

Heart valve disease leads to approximately 300,000 heart valve replacement surgeries each year worldwide. Valvular interstitial cells (VICs) are believed to play a vital role in the repair of heart valves and also most disease processes. VICs synthesize, remodel, and repair the ECM; however, when VICs excessively differentiate to the highly contractile and synthetic myofibroblast phenotype, valvular fibrosis may ensue. Elevated mechanical stress triggers the differentiation of VICs into myofibroblasts. Transforming growth factor beta-1 (TGF-β1) is also critical for the formation of thicker stress fibers positive for α-smooth muscle actin (α-SMA), the defining characteristic of myofibroblasts.Copyright

Advanced human coronary plaque wall thickness correlates positively with flow shear stress and negatively with plaque wall stress: An IVUS-based FSI study

Conference Name:ASME 2013 Summer Bioengineering Conference, SBC 2013. Conference Address: Sunriver, OR, United states. Time:June 26, 2013 - June 29, 2013.

A Novel Surgical Approach Using Contracting Band to Improve Right Ventricle Ejection Fraction for Patients With Repaired Tetralogy of Fallot, a Patient-Specific CMR-Based Modeling Study

Patients with repaired Tetralogy of Fallot (ToF) account for the majority of cases with late onset right ventricle (RV) failure. The current surgical approach, which includes pulmonary valve replacement/insertion (PVR), has yielded mixed results [1–2]. A new surgical option placing an elastic band in the right ventricle is proposed to improve RV cardiac function measured by ejection fraction (EF).Copyright

A Framework to Assess Human Coronary Plaque Vulnerability Using Intravascular Ultrasound, On-Site Pressure, Angiography, and Anisotropic FSI Models

Atherosclerotic plaque rupture is believed to be associated with critical flow and stress/strain conditions. Image-based computational models have been developed to identify critical flow and stress/strain conditions in the plaque [1–3]. In vivo image-based coronary plaque modeling papers are relatively rare because clinical recognition of vulnerable coronary plaques has remained challenging [4]. In this paper, a framework adopting intravascular ultrasound (IVUS) imaging with on-site pressure and flow measurements, biaxial mechanical testing and computational modeling is proposed to construct 3D coronary plaque for more accurate stress/strain predictions.© 2012 ASME