COMPARISON OF ANALYTICAL AND FINITE ELEMENT IMPLEMENTATION OF EXPONENTIAL CONSTITUTIVE MODELS FOR VALVE TISSUE UNDER MICROPIPETTE ASPIRATION SBC2010-19245

INTROUDUCTION Micropipette aspiration (MA) has been widely used to measure the biomechanical properties of cells and biomaterials The goal of this study was to determine whether aortic valve tissue material parameters estimated by the easily-implemented analytical approach [3] differ from those obtained by finite element (FE) analysis aortic valve tissue under MA. To do so, we implemented an exponential hyperelastic constitutive model in the FE model and used an inverse FE approach to predict material parameters METHODS AND MATERIALS Material models To fit the MA experimental measurements of the embryonic atrioventricular cushions, Butcher et al. implemented an exponential constitutive model [2] where W is the strain energy, C and α are material constants and E is the Green's finite strain with the 2 nd Piola-Kirchoff stress (S) being calculated by S = ∂W/∂E. To relate the stress and strain in the constitutive model to experimental measurements, Butcher et al. directly assigned the measured aspiration length (L) to pipette radius (a) ratio as the Green's strain, and the measured aspiration pressure ΔP as the Lagrangian stress T, which is calculated by T = λS with the stretch ratio in the aspiration direction (λ) given by λ = (E + 1) 0.5 To account for the multicomponent stress-strain field in the valve tissue during MA process, we implemented an incompressible isotropic exponential constitutive model. The strain energy density function of this model is expressed as where W is the strain energy, C and α are material constants and I 1 is the first strain invariant, defined as I 1 = with λ 1 , λ 2 and λ 3 being the principal stretches. This isotropic exponential constitutiv

The Development and Application of Tools to Study the Multiscale Biomechanics of the Aortic Valve

Calcific aortic valve disease (CAVD) is one of the most common causes of cardiovascular disease in North America. Mechanical factors have been closely linked to the pathogenesis of CAVD and may contribute to the disease by actively regulating the mechanobiology of valve interstitial cells (VICs). Mechanical forces affect VIC function through interactions between the VIC and the extracellular matrix (ECM). Studies have shown that the transfer of mechanical stimulus during cell-ECM interaction depends on the local material properties at hierarchical length scales encompassing tissue, cell and cytoskeleton. In this thesis, biomechanical tools were developed and applied to investigate hierarchical cell-ECM interactions, using VICs and valve tissue as a model system. Four topics of critical importance to understanding VIC-ECM interactions were studied: focal biomechanical material properties of aortic valve tissue; viscoelastic properties of VICs; transduction of mechanical deformation from the ECM to the cytoskeletal network; and the impact of altered cell-ECM interactions on VIC survival. To measure focal valve tissue properties, a micropipette aspiration (MA) method was implemented and validated. It was found that nonlinear elastic properties of the top layer of a multilayered biomaterial can be estimated by MA by using a pipette with a diameter smaller than the top layer thickness. Using this approach, it was shown that the effective stiffness of the fibrosa layer is greater than that of the ventricularis layer in intact aortic valve leaflets (p<0.01). To characterize the viscoelastic properties of VICs, an inverse FE method of single cell MA was developed and compared with the analytical half-space model. It was found that inherent differences in the half-space and FE models of single cell MA yield different cell viscoelastic material parameters. However, under particular experimental conditions, the parameters estimated by the half-space model are statistically indistinguishable from those predicted by the FE model. To study strain transduction from the ECM to cytoskeleton, an improved texture correlation algorithm and a uniaxial tension release device were developed. It was found that substrate strain fully transfers to the cytoskeletal network via focal adhesions in live VICs under large strain tension release. To study the effects of cell-ECM interactions on VIC survival, two mechanical stimulus systems that can simulate the separate effects of cell contraction and cell monolayer detachment were developed. It was found that cell sheet detachment and disrupted cell-ECM signaling is likely responsible for the apoptosis of VICs grown in culture on thin collagen matrices, leading to calcification. The studies presented in this thesis refine existing biomechanical tools and provide new experimental and analytical tools with which to study cell-ECM interactions. Their application resulted in an improved understanding of hierarchical valve biomechanics, mechanotransduction, and mechanobiology.Ph

Recent Advances in CXCL12/CXCR4 Antagonists and Nano-Based Drug Delivery Systems for Cancer Therapy

Chemokines can induce chemotactic cell migration by interacting with G protein-coupled receptors to play a significant regulatory role in the development of cancer. CXC chemokine-12 (CXCL12) can specifically bind to CXC chemokine receptor 4 (CXCR4) and is closely associated with the progression of cancer via multiple signaling pathways. Over recent years, many CXCR4 antagonists have been tested in clinical trials; however, Plerixafor (AMD3100) is the only drug that has been approved for marketing thus far. In this review, we first summarize the mechanisms that mediate the physiological effects of the CXCL12/CXCR4 axis. Then, we describe the use of CXCL12/CXCR4 antagonists. Finally, we discuss the use of nano-based drug delivery systems that exert action on the CXCL12/CXCR4 biological axis

NANOG restores the impaired myogenic differentiation potential of skeletal myoblasts after multiple population doublings

Adult skeletal muscle regeneration relies on the activity of satellite cells residing in the skeletal muscle niche. However, systemic and intrinsic factors decrease the myogenic differentiation potential of satellite cells thereby impairing muscle regeneration. Here we present data showing that late passage C2C12 myoblasts exhibited significantly impaired myogenic differentiation potential that was accompanied by impaired expression of myogenic regulatory factors (Myf5, MyoD, Myogenin, and MRF4) and members of myocyte enhancer factor 2 family. Notably, ectopic expression of NANOG preserved the morphology and restored the myogenic differentiation capacity of late passage myoblasts, possibly by restoring the expression level of these myogenic factors. Muscle regeneration was effective in 2D cultures and in 3D skeletal microtissues mimicking the skeletal muscle niche. The presence of NANOG was required for at least 15 days to reverse the impaired differentiation potential of myoblasts. However, it was critical to remove NANOG during the process of maturation, as it inhibited myotube formation. Finally, myoblasts that were primed by NANOG maintained their differentiation capacity for 20 days after NANOG withdrawal, suggesting potential epigenetic changes. In conclusion, these results shed light on the potential of NANOG to restore the myogenic differentiation potential of myoblasts, which is impaired after multiple rounds of cellular division, and to reverse the loss of muscle regeneration. Keywords: Aging, Skeletal muscle loss, Sarcopenia, Satellite cells, C2C12 myoblasts, Myogenic differentiatio

Decoupling Cell and Matrix Mechanics in Engineered Microtissues Using Magnetically Actuated Microcantilevers

International audienceA novel bio-magnetomechanical microtissue system is described for magnetic actuation of arrays of 3D microtissues using microcantilevers. This system enables both in situ measurements of fundamental mechanical properties of engineered tissue, such as contractility and stiffness, as well as dynamic stimulation of the microtissues. Using this system, cell and extracellular matrix contributions to the tissue mechanical properties are decoupled for the first time under both static and dynamic loading conditions

Parametric finite element study on slotted rectangular and square HSS tension connections

A parametric finite element analysis study was carried out on slotted rectangular and square hollow structural section (HSS) tension connections without welding at the end of the gusset plate for different weld length ratio, slot orientation, weld size and level of HSS corner strength compared to its flat segment. Finite element models for the parametric study were developed and validated against test results of the connection with the tube slotted. The modified weld length ratio was found to be a better parameter than the modified eccentricity ratio in characterizing the net section efficiency of a slotted HSS tension member when the weld length is short. Improvements to provisions in CSA-S16-01 and ANSI/AISC-360-05 for slotted tubular tension connections were proposed based on results of the study

Additional file 1 of Tobacco and menthol flavored nicotine-free electronic cigarettes induced inflammation and dysregulated repair in lung fibroblast and epithelium

Supplementary Material 1: Full western blot images reflecting all blots/bands are given in Suppl Fig