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The developing zebrafish ventricle generates higher intraventricular pressure (IVP) with increasing stroke volume and cardiac output at different developmental stages to meet the metabolic demands of the rapidly growing embryo (Salehin et al. Ann Biomed Eng, 2021;49(9): 2080-2093). To understand the changing role of the developing embryonic heart, we studied its biomechanical characteristics during in vivo cardiac cycles. By combining changes in wall strains and IVP measurements, we assessed ventricular wall stiffness during diastolic filling and the ensuing systolic IVP-generation capacity during 3-, 4-, and 5-day post fertilization (dpf). We further examined the anisotropy of wall deformation, in different regions within the ventricle, throughout a complete cardiac cycle.We found the ventricular walls grow increasingly stiff during diastolic filling with a corresponding increase in IVP-generation capacity from 3- to 4- and 5-dpf groups. In addition, we found the corresponding increasing level of anisotropic wall deformation through cardiac cycles that favor the latitudinal direction, with the most pronounced found in the equatorial region of the ventricle.From 3- to 4- and 5-dpf groups, the ventricular wall myocardium undergoes increasing level of anisotropic deformation. This, in combination with the increasing wall stiffness and IVP-generation capacity, allows the developing heart to effectively pump blood to meet the rapidly growing embryo's needs.

The use of mathematical and numerical techniques to elucidate arterial hemodynamics has increased in recent years owing to the prevalence of arterial diseases. Many works have appeared employing three-dimensional models to simulate blood flow in arteries. However, this comes at a huge computational cost and power. In this work, a mathematical model for simulating and predicting blood flow dynamics in an arterial vessel has been developed to meet the teeming need for a computationally-cheap numerical model. The time-dependent one-dimensional hyperbolic system of quasilinear partial differential equations was established from the consideration of physical conservation laws of momentum and mass. This fluid-structure interaction model also incorporates an elastic mural model of the compliant arterial wall material. The combined arterial flow model was solved to simulate flow in the iliac artery using the method of lines. The results revealed that arterial hemodynamics can be adequately captured by a one-dimensional model as proposed. Also, the simulations generated for idealized healthy states could serve as a base model for the numerical simulation of diseased states in the artery.

During embryogenesis, the developing heart transforms from a linear peristaltic tube into a multi-chambered pulsatile pump with blood flow-regulating valves. In this work, we report how hemodynamic parameters evolve during the heart's development, leading to its rhythmic pumping and blood flow regulation as a functioning organ. We measured the time course of intra-ventricular pressure from zebrafish embryos at 3, 4, and 5 days post fertilization (dpf) using the servo null method. We also measured the ventricular volume and monitored the opening/closing activity of the AV and VB valves using 4D selective plane illumination microscopy (SPIM). Our results revealed significant increases in peak systolic pressure, stroke volume and work, cardiac output, and power generation, and a total peripheral resistance decrease from zebrafish at 4, 5 dpf versus 3 dpf. These data illustrate that the early-stage zebrafish heart's increasing efficiency is synchronous with the expected changes in valve development, chamber morphology and increasing vascular network complexity. Such physiological measurements in tractable laboratory model organisms are critical for understanding how gene variants may affect phenotype. As the zebrafish emerges as a leading biomedical model organism, the ability to effectively measure its physiology is critical to its translational relevance.

Using a microfluidic platform to apply negative aspiration pressure (–20, –25, –30, –35 and –40 cm H2O), we compared the differences in creep responses of Glioblastoma Multiforme (GBM) cells while migrating in confinement and at a stationary state on a 2D substrate. Cells were either migrating in a channel of 5 x 5 μm cross-section or stationary at the entrance to the channel. In response to aspiration pressure, we found actively migrating GBM cells exhibited a higher stiffness than stationary cells. Additionally, migrating cells absorbed more energy elastically with a relatively small dissipative energy loss. At elevated negative pressure loads up to – 30 cm H2O, we observed a linear increase in elastic deformation and a higher distribution in elastic storage than energy loss, and the response plateaued at further increasing negative pressure loads. To explore the underlying cause, we carried out immuno-cytochemical studies of these cells and found a polarized actin and myosin distribution at the front and posterior ends of the migrating cells, whereas the distribution of the stationary group demonstrated no specific regional differences. These differences in creep response and cytoskeletal protein distribution demonstrate the importance of a migrating cell’s kinematic state to the mechanism of cell migration.

In vivo quantitative assessment of structural and functional biomarkers is essential for understanding pathophysiology and identifying novel therapies for congenital heart disorders. Cardiac defect analysis through fixed tissue and histology has offered revolutionary insights into the tissue architecture, but section thickness limits the tissue penetration. This study demonstrated the potential of Light Sheet Fluorescence Microscopy (LSFM) for analyzing in vivo 4D (3d + time) cardiac contractility. Furthermore, we have described the utility of an improved feature detection framework for localizing cardiomyocyte nuclei in the zebrafish atrium and ventricle. Using the Hessian Difference of Gaussian (HDoG) scale space in conjunction with the watershed algorithm, we were able to quantify a statistically significant increase in cardiomyocyte nuclei count across different developmental stages.Furthermore, we assessed individual volumes and surface areas for the cardiomyocyte nuclei in the ventricle’s innermost and outermost curvature during cardiac systole and diastole. Using the segmented nuclei volumes from the feature detection, we successfully performed local area ratio analysis to quantify the degree of deformation suffered by the outermost ventricular region compared to the innermost ventricular region. This paper focuses on the merits of our segmentation and demonstrates its efficacy for cell counting and morphology analysis in the presence of anisotropic illumination across the field-of-view (FOV).

Aims To critically review studies of the biomechanical properties of connective tissue in the normal and prolapsed human vaginal wall and to identify criteria that are suitable for in vivo measurements which could improve patient management. Methods This review covers past and current ex vivo and in vivo instrumentation and analytical methods related to the elastic and viscoelastic properties of vaginal wall connective tissues. Results Classical methods, including digital evaluation of the vagina, histological and biomechanical studies of fresh and frozen-thawed extracts, and biomechanical cadaveric tissue studies have important limitations and have yielded inconsistent results. Newer biomechanical methods may resolve these inconsistencies. One of the more promising is transient, vacuum-induced tissue expansion and relaxation, via cutometer-like devices. The technique permits noninvasive observation, applicable to longitudinal studies of patients. In vivo and ex vivo biomechanical methods may better match vaginal wall tissue properties to help with the design of surgical mesh materials, thus improving surgical support and healing. Conclusion Methods have been identified to characterize the in vivo biomechanical behavior of the prolapsing vagina which may serve to advance the care of affected women. Neurourol. Urodynam. © 2016 Wiley Periodicals, Inc.

Wall injury is observed during stent expansion within atherosclerotic arteries, related in part to stimulation of the inflammatory process. Wall stress and strain induced by stent expansion can be closely examined by finite element analysis (FEA), thus shedding light on procedure-induced sources of inflammation. The purpose of this work was to use FEA to examine the interaction of a coiled polymer stent with a plaque-containing arterial wall during stent expansion. An asymmetric fibrotic plaque-containing arterial wall model was created from intravascular ultrasound (IVUS) images of a diseased artery. A 3D model for a coil stent at unexpanded state was generated in SolidWorks. They were imported into ANSYS for FEA of combined stent expansion and fibrotic plaque-distortion. We simulated the stent expansion in the plaqued lumen by increasing balloon pressure from 0 to 12 atm in 1 atm step. At increasing pressure, we examined how the expanding stent exerts forces on the fibrotic plaque and vascular wall components, and how the latter collectively resist and balance the expansive forces from the stent. Results show the expanding coiled stent creates high stresses within the plaque and the surrounding fibrotic capsule. Lower stresses were observed in adjacent medial and adventitial layers. High principal strains were observed in plaque and fibrotic capsule. The results suggest fibrotic capsule rupture might occur at localized regions. The FEA/IVUS method can be adapted for routine examination of the effects of the expansion of selected furled stents against IVUS-reconstructed diseased vessels, to improve stent deployment practices.

In the injured adult nervous system, re-establishment of growth-promoting molecular gradients is known to entice and guide nerve repair. However, incorporation of three-dimensional chemotactic gradients in nerve repair scaffolds, particularly in those with multi-luminal architectures, remains extremely challenging. We developed a method that establishes highly tunable three-dimensional molecular gradients in multi-luminal nerve guides by anchoring growth-factor releasing coiled polymeric fibers onto the walls of collagen-filled hydrogel microchannels. Differential pitch in the coiling of neurotrophin-eluting fibers generated sustained chemotactic gradients that appropriately induced the differentiation of Pheochromocytoma (PC12) cells into neural-like cells along an increasing concentration of nerve growth factor (NGF). Computer modeling estimated the stability of the molecular gradient within the luminal collagen, which we confirmed by observing the significant effects of neurotrophin gradients on axonal growth from dorsal root ganglia (DRG). Neurons growing in microchannels exposed to a NGF gradient showed a 60% increase in axonal length compared to those treated with a linear growth factor concentration. In addition, a two-fold increment in the linearity of axonal growth within the microchannels was observed and confirmed by a significant reduction in the turning angle ratios of individual axons. These data demonstrate the ability of growth factor-loaded polymeric coiled fibers to establish three-dimensional chemotactic gradients to promote and direct nerve regeneration in the nervous system and provides a unique platform for molecularly guided tissue repair.

Uncontrolled invasive cancer cell migration is among the major challenges for the treatment and management of brain cancer. Although the genetic profiles of brain cancer cells have been well characterized, the relationship between the genetic mutations and the cells’ mobility has not been clearly understood. In this study, using microfluidic devices that provide a wide range of physical confinements from 20 × 5 μm2 to 3 × 5 μm2 in cross sections, we studied the effect of physical confinement on the migratory capacity of cell lines with different types of mutations. Human glioblastoma and genetically modified mouse astrocytes were used. Human glioblastoma cells with EGFRvIII mutation were found to exhibit high degree of migratory capacity in narrow confinement. From mouse astrocytes, cells with triple mutations (p53−/− PTEN−/− BRAF) were found to exhibit the highest level of migratory capacity in narrow confinement compared to both double (p53−/− PTEN−/−) and single (p53−/−) mutant cells. Furthermore, when treating the triple mutant astrocytes with AZD-6244, an inhibitor of the RAF/MEK/ERK pathway, we found significant reduction in migration through the confined channels when compared to that of controls (83% decrease in 5 × 5 μm2 and 86% in 3 × 5 μm2 channels). Our data correlate genetic mutations from different cell lines to their motility in different degrees of confinement. Our results also suggest a potential therapeutic target such as BRAF oncogene for inhibition of brain cancer invasion.

To investigate the influence of elevated annealing temperature (70–90 °C) on the mechanical properties of coiled helical PLLA stents. PLLA 0.10 mm fibers and O3 mm × 12 mm stents were fabricated and annealed at 70, 80 and 90 °C for 25 min. The mechanical properties of the fibers and the functional characteristics of the stents were measured and compared to a control group processed at 21 °C. The stents were mounted, expanded and relaxed using an O3 mm × 2 cm balloon catheter to a maximum balloon pressure of 12 atm. Measurements of stent diameter, length, and the balloon pressure were used to determine the effective circumferential strain, incremental stiffness, elastic recoil, and lengthening of the stents. Stents exhibited progressively higher incremental stiffness with annealing temperature, higher collapse resistance and a reduction in elastic recoil vs. controls. Single fiber mechanical properties decreased as annealing temperature increased. Differential scanning calorimetry revealed crystallinity increased within thermally annealed stent fibers compared with controls. SEM examination indicated thermally annealed stents underwent less twisting than controls during balloon-induced unfurling. Thermal annealing of PLLA fibers and stents between 70 and 90 °C induced changes in crystalline structure, thereby favorably influencing fiber stress–strain behavior and stent expansion characteristics.

Brain tumor cells remain highly resistant to radiation and chemotherapy, particularly malignant and secondary cancers. In this study, we utilized microchannel devices to examine the effect of a confined environment on the viability and drug resistance of the following brain cancer cell lines: primary cancers (glioblastoma multiforme and neuroblastoma), human brain cancer cell lines (D54 and D54-EGFRvIII) and genetically modified mouse astrocytes (wild type, p53−/−, p53−/− PTEN−/−, p53−/− Braf and p53−/− PTEN−/− Braf). We found that loss of PTEN combined with Braf activation resulted in higher viability in narrow microchannels. In addition, Braf conferred increased resistance to the microtubule-stabilizing drug Taxol in narrow confinement. Similarly, survival of D54-EGFRvIII cells was unaffected following treatment with Taxol, whereas the viability of D54 cells was reduced by 75% under these conditions. Taken together, our data suggests key targets for anticancer drugs based on cellular genotypes and their specific survival phenotypes during confined migration.

We studied the effects of thermal treatment on the expansive characteristics of a coil-within-coil Poly(L-lactic acid) (PLLA) fiber stent developed at our institution to improve its mechanical performance and reproducibility. Following fabrication, furled stents were thermally treated at 62 degrees C for 25 min. The mechanical characteristics were measured compared with those of untreated stents when both were expanded via sequential balloon catheter pressure loading up to 12 atm. Treated stents reached full diameter at 3 atm and maintained that diameter despite further pressure increases. Using measurements of pressure, diameter, and axial length, we calculated the sequential mechanical work required to unfurl the stent. The mechanical work for complete unfurling of treated stents was significantly less than that required for untreated controls. Little axial dimensional change was observed for treated stents. Treated stents exhibited higher stiffness than controls at all pressure levels and also demonstrated higher resistance to external pressure-induced collapse, as measured in a special apparatus developed in our laboratory. Differential scanning calorimetry measurements indicated higher crystallinity values for fibers used in treated stents compared with controls. SEM examination of striations revealed that treated stents underwent less twist than controls following balloon-induced unfurling. The results indicate that, thermal treatment improves the reorientation and realignment of fiber crystalline structure, and favorably influences on the fiber stress-strain behavior and the expansive mechanical characteristics of the PLLA fiber stents.

Deposition of thin polymeric films on nanoporous membranes is shown to provide a mechanically simple and inexpensive approach to regulate trans-membrane gas flows. For this purpose, polymeric films were deposited on polycarbonate track-etched (PCTE) membranes of 50 nm and 100 nm pore size. The films were generated by low-pressure glow discharge plasma polymerization of vinyl acetic acid (CH2 CHCH2COOH) or perfluorohexane (n-C6F14) monomers. The plasma discharge was operated under pulsed conditions to provide better control of the polymeric film chemistry along with improved control of film thickness. The gradual reduction in average membrane pore sizes with increasing film thickness resulted in controlled decreases in the permeation rates of O2 and CO2 gases. In addition to film thickness, the permeation rates were observed to be functions of the specific composition and cross-link density of the polymer films deposited, as well as the nature of the permeant gases. It was determined that the plasma deposition process employed provides sufficient permeation control for use in applications requiring fine modulation of gas permeation rate such as those encountered in development of a blood oxygenator, a major motivation for the present study.

Polymeric vascular stents must employ other strategies than malleable deformation, as generally practiced with metal stents, to expand and withstand compressive stresses in situ. The stent expansion strategy must further consider induced flow perturbations and wall stresses that may injure the vessel wall and promote thrombogenesis. Analyzing the stresses furled stents undergo during balloon-assisted expansion is an important first step in achieving a better understanding of stent-wall mechanical interactions, thereby to improve stent function. To this end, we performed finite element (FE) analysis of the balloon-induced unfurling of an internally coiled, bioresorbable polymeric stent employing a 3D FE solid model of a 120 degrees symmetric stent segment and a large deformation finite strain formulation. Uni-axial tensile testing of stent fiber elastic to plastic yielding provided the mechanical property information, and the von Mises criterion was employed to establish the elastic-plastic transition in the FE model. The model was validated with pressure and deformation measurements obtained during stent expansion tests. The internal coils of this inner coil-outer coil design twisted as the stent expanded, leading to plastic yielding at the point of tangency of the inner and outer coils. The remaining stent fiber portions underwent elastic bending. Cross-sections revealed only the outside surface layer of the coiled fiber underwent plastic yielding. The interior elastic fiber was supported by this plastic shell. The analysis suggests that during balloon-induced expansion, local plastic yielding in torsion "sets" the stent fibers, imparting high radial collapse resistance. The results further suggest that the stent exerts non-uniform mechanical forces on the vessel wall during expansion.

To critically review studies of the biomechanical properties of connective tissue in the normal and prolapsed human vaginal wall and to identify criteria that are suitable for in vivo measurements which could improve patient management.This review covers past and current ex vivo and in vivo instrumentation and analytical methods related to the elastic and viscoelastic properties of vaginal wall connective tissues.Classical methods, including digital evaluation of the vagina, histological and biomechanical studies of fresh and frozen-thawed extracts, and biomechanical cadaveric tissue studies have important limitations and have yielded inconsistent results. Newer biomechanical methods may resolve these inconsistencies. One of the more promising is transient, vacuum-induced tissue expansion and relaxation, via cutometer-like devices. The technique permits noninvasive observation, applicable to longitudinal studies of patients. In vivo and ex vivo biomechanical methods may better match vaginal wall tissue properties to help with the design of surgical mesh materials, thus improving surgical support and healing.Methods have been identified to characterize the in vivo biomechanical behavior of the prolapsing vagina which may serve to advance the care of affected women. Neurourol. Urodynam. 36:499-506, 2017. © 2016 Wiley Periodicals, Inc.

Purpose Using finite element (FE) computer model simulation, we compared the mechanical characteristics of the mandible after bilateral sagittal split ramus osteotomy (BSSRO) through the use of 2 different techniques to stabilize the osteotomy. Materials and methods Based on the reconstructed geometry from computed tomography scans of dry adult skull with a mandibular deformity requiring surgical correction, we developed 3-dimensional FE models that simulate BSSRO with 2 different techniques to stabilize the osteotomy. Technique 1 uses 3 bicortical titanium screws. Technique 2 uses a curved titanium plate with 4 monocortical screws. Five different load cases were applied to the mandible after the simulated BSSRO with the mandible being constrained at both temporomandibular joints. To evaluate the efficacy of these 2 stabilization techniques, we compared 1) the resulting deflections at the central incisor, 2) the mechanical stresses developed in the bone in the vicinity of the stabilizing implants, and 3) the mechanical stresses developed within the screw/plating system themselves. Results Technique 1, using 3 bicortical titanium screws, leads to smaller deflections at the central incisor for all 5 load cases, suggesting higher mechanical stability. Technique 1 also leads to lower mechanical stresses in the bone and in the implanted screws, whereas technique 2 is associated with higher values in each of these quantities. Conclusions To stabilize osteotomies after a 3-dimensional simulated BSSRO, 3 bicortical screws forming an inverted-L configuration are shown to offer more effective load transmission in the mandibular construct. This technique, when examined in an FE model, leads to higher stability with lower mechanical stresses in the bone near the bicortical screws.

We report the influence of body mass index (BMI) on the biomechanical properties of human prolapsed anterior vaginal wall (AVW) tissue samples. We hypothesize that women with AVW prolapse would have the same vaginal wall biomechanical properties regardless of their weight.Following Institutional Review Board approval, age-comparable postmenopausal women with symptomatic stage II-III AVW prolapse underwent excision of a short vaginal wall sample during transvaginal prolapse repair. Excised samples were subjected to uniaxial tensile testing using an Instron 5655 (Instron, Norwood, MA, USA) within 2 h of harvest to measure intrinsic biomechanical properties. Patients were divided into two groups (A: BMI25 and B: BMI25) to compare tissue biomechanical properties after controlling for age and parity.From 2011 to 2013, 28 consecutive women were studied, 13 in group A and 15 in group B. Patients with BMI25 developed higher tissue stresses, including higher tangent moduli, at selected strain levels than patients with BMI25.Contrary to our hypothesis, this study observed a relationship between BMI and human AVW biomechanical properties, with more obese women having stiffer tissue properties.

Although it is known that cells promote structural reorganization of the collagen architecture, how individual cells exert mechanical tension on the matrix is not clearly understood. In the present study we have investigated the mechanical interaction of individual corneal fibroblasts with a collagen matrix using an improved version of our previously described in vitro force-measurement system (Roy, P. et al. Exp. Cell Res. 232:106-117, 1997). The elastic distortion of the collagen matrix exerted by cells was temporally recorded and analyzed using a two-dimensional finite-element model to quantify the forces exerted on the matrix. Time-lapse videomicroscopy of serum-cultured cells on the matrix for up to 6 h revealed that individual fibroblasts generated measurable tension on the matrix during pseudopodial extension and slow retraction. Fast retraction, an event observed during active cell migration, was associated with dramatic release of tension on the matrix. An apparent inverse correlation was observed between cell translocation and maintenance of matrix tension. Additional experiments with cells under serum-free conditions revealed that these cells fail to generate any detectable tension on the matrix despite undergoing filopodial extension and retraction. Since serum-free cells do not form focal adhesions or stress fibers, these experimental data suggest that contractility of nonmotile cells, coupled with strong cell-matrix adhesion, is the most favorable mechanism of generating and maintaining tension on the extracellular matrix.

To facilitate bioprosthetic heart valve design, especially in the use of novel antimineralization chemical technologies, a thorough understanding of the multiaxial mechanical properties of chemically treated bovine pericardium (BP) is needed. In this study, we utilized a small angle light scattering based tissue pre-sorting procedure to select BP specimens with a high degree of structural uniformity. Both conventional glutaraldehyde (GL) and photo-oxidation (PO) chemical treatment groups were studied, with untreated tissue used as the control group. A second set of GL and PO groups was prepared by prestretching them along the preferred fiber direction during the chemical treatment. An extensive biaxial test protocol was used and the resulting stress-strain data fitted to an exponential strain energy function. The high structural uniformity resulted in both a consistent mechanical response and low variability in the material constants. For free fixed tissues, the strain energy per unit volume for GL treated BP was ∼ 2.8 times that of PO treated BP at an equibiaxial Green’s strain level of 0.16. Prestretched tissues exhibited a profound increase in both stiffness and the degree of anisotropy, with the GL treatment demonstrating a greater effect. Thus, structural control leads to an improved understanding of chemically treated BP mechanical properties. Judicious use of this knowledge can facilitate the design and enhanced long-term performance of bioprosthetic heart valves. © 1998 Biomedical Engineering Society. PAC98: 8790+y, 8745Bp, 8780+s

Objective In-vivo measurement of the viscoelastic properties of the prolapsed anterior vaginal wall (AVW) in post-menopausal women undergoing cystocele repair. Study design A BTC-2000™ cutometer-like instrument was introduced during vaginal repair of symptomatic stage 2–3 AVW prolapse. Under anesthesia, 10-mm orifice probe was applied to the AVW at the level of the bladder neck. A suction pressure ramp (0 to −147mmHg in 6s) was delivered causing tissue uplift, followed by immediate release to 0mmHg, measuring tissue relaxation for 20s. Similar measurements were performed over the suprapubic region (SP) for comparison purpose. The rate of tissue recovery was obtained by fitting a Voigt model to the data and expressing results as the ratio E / η [(spring modulus E )/(dashpot viscosity η )]. The effective strain energy (SE) was calculated from the pressure-uplift data and evaluated from initiation to: (1) maximum storage in tissue at peak vacuum; (2) tissue recovery after vacuum release; (3) net SE loss over the entire loading-unloading cycle. Results In 22 women, higher AVW peak and residual tissue uplift values, and lower E / η ratios were found compared with SP results. The AVW stored less elastic strain energy at peak vacuum than did the SP, and AVW net energy loss over the uplift-recovery cycle was greater than for SP controls. Not only was the AVW more compliant than the SP, with higher viscous damping, but the tissue was also less able to store recoverable energy upon distension. Conclusion Such in-vivo measurements quantify the biomechanical properties of the prolapsed AVW and may assist in its management.

Cryopreservation of engineered tissue equivalents (TE) has achieved limited success. Successful preservation of a functional TE or tissue could provide prolonged transplantation time windows or off-the-shelf availability of engineered tissues. A quantitative understanding of the freezing-induced cell-fluid-matrix mechanical interaction is critical towards successful preservation of functional tissue. Using quantum dot-mediated cell image deformetry, Teo et al have experimentally mapped the instantaneous deformation of a TE during freezing process and showed its resulting volume change after thawing due to fluid loss [1]. To further our understanding of the freezing-induced fluid-matrix interaction, we have developed a biphasic model that simulates the transient of thermal load, its resulting TE elastic deformation, the corresponding pressure redistribution within, and the fluid movement in the TE.Copyright © 2011 by ASME

Vascular smooth muscle cells (VSMCs) are constantly exposed to cyclic stretch in the body, which makes it beneficial to study the effects of cyclic stretch on VSMCs. In this study, we developed a poly(dimethyl siloxane) (PDMS) compact six-well device that can be used to study the combined effect of cyclic strain and various growth factors on cultured VSMCs. Cell adhesion, alignment, and proliferation under 10% or 20% cyclic strain at 1 Hz were studied using this surface-enhanced PDMS device. The combined effects of cyclic strain with either transforming growth factor-β, vascular endothelial growth factor, fibroblast growth factor, or epidermal growth factor on VSMC proliferation was also examined. Results showed that VSMCs adhered well on the surface-enhanced multiwell device and they aligned perpendicularly to the direction of the cyclic strain. Cell proliferation was inhibited by 10% cyclic strain at 1 Hz compared with static control. The mitogenic effects of the growth factor were less potent under either 10% or 20% cyclic strain. With simple modification to accommodate more wells, this device could potentially be a useful tool for more economical, high throughput screening application.

We applied the pseudostrain energy function of Humphrey et al. [J. biomech. Engng 112, 333-346 (1990a, b)] to characterize the passive biaxial mechanical properties of the right ventricle free wall myocardium [Sacks and Chuong, J. biomech. Engng 115, 202-205 (1993)]. The myocardium was assumed to be incompressible, pseudoelastic, and transversely isotropic, with transmural variations in fiber orientation within test specimens accounted for by the strain energy function. Using nonlinear regression, material constants were determined for the right ventricle free wall myocardium from the sinus and conus regions. The pseudostrain energy function was found to model the biaxial mechanical data well (r20.99). Transmural variations in Cauchy stresses, as well as the magnitude of the in-plane shear stress, were found to be small. Although comparisons with the left ventricle midwall myocardium data [Humphrey et al., J. biomech. Engng 112, 340-346 (1990b)] show clear quantitative differences, there is an overall qualitative similarity in the mechanical behavior of ventricular myocardium.

A prerequisite to biomedical analyses of the right ventricular free wall (RVFW) is the characterization of its in vivo geometry and instantaneous wall thickness (WT). We present a method to reconstruct and mathematically model the in vivo RVFW surface geometry using ECG-gated magnetic resonance imaging (MRI). From digitized contours we reconstructed the endo- and epicardial surfaces of the entire heart, and approximated the RVFW surface geometry by local biquadric surface patches. An insurface coordinate system was developed, with respect to which the metric tensor, curvature tensor, major (k2), and minor (k1) principal curvatures were computed. The method was evaluated using MRI data from one dog, which showed that k2 was about 10 times k1, with k2 and k1 approximately perpendicular and parallel to the RV long axis, respectively. During systole, k1 and both principal curvature directions remained essentially unchanged, while k2 revealed only a 7% decrease (rho0.05) in the sinus region. These results suggest that while the RVFW undergoes small changes in surface geometry during systole, its overall curvature remained constant. The WT/mean radius of curvature ratio was less than 0.1 during systole throughout the RVFW, indicating it can be idealized as a thin shell.

Stents have been used as a medical device to restore blood flow in stenosed vessels. During this process of stent expansion, the balloon and stent could damage the endothelial lining of the vascular wall [Grewe, Farb] and alter the mechanical stress states of various tissue components. The subsequent tissue re-growth and vascular remodeling have been implicated among the causes leading to restenosis. Stent designs vary over a wide range from materials used, geometric shapes, fabrication methods, treatments, among many other parameters. There are many different stent designs. We have developed an internally coiled, furled helical PLLA fiber stent at our institution [Su 03, Zilberman 02, 04, 05]. We have previously shown the effect of 62°C thermal annealing on the expansive characteristics of this stent [Welch 08].Copyright © 2009 by ASME

Stents are a medical device used to restore blood flow in stenosed vessels. During the process of stent expansion, the balloon and stent could damage the endothelial lining of the vascular wall and alter the mechanical stress states of various tissue components. The evolution of stents has progressed from bare metal stents to drug eluting stents or stents coated with drugs such as Sirolimus. Drug eluting stents are currently used to address the restenosis event that occurs after implantation. These stents have been effective but late stent thrombosis has been an emerging issue with drug eluting stents. Bioresorbable stents have emerged as a potential candidate for drug eluting stents. Su 03 has shown drug-loading PLLA with curcumin can be used as an anti-inflammatory agent. We have developed an internally coiled, furled helical PLLA fiber stent at our institution [Su 03, Zilberman 02, 04, 05]. We have previously shown the effect of 62°C thermal annealing on the expansive characteristics of this stent [Welch 08].Copyright © 2009 by ASME

Nanostructured membranes with precisely engineered nanopores were fabricated on a thin silicon nitride membrane, using a combination of bulk micromachining and focused-ion-beam drilling. These membranes are designed to preserve microscale blood channel dimensions, thereby permitting the red cell shape change that enhances gas exchange in the pulmonary capillary. The membranes were tested for their mechanical stability and the results were verified with finite element analysis. Initial studies have proven the membranes to be robust, and capable of withstanding pressures typically experienced in blood oxygenator channels. A novel MEMS-based blood oxygenation system employing the nanoporous membranes is also presented. The oxygenation system is designed to have controlled blood and gas volumes for efficient blood oxygenation.

Stent navigation and expansion may injure vascular endothelium, including vulnerable plaque lesions. Balloon expansion and deployment of a stent can lead to injury or the endothelial lining and stretching of the arterial wall [1]. Understanding the traction forces an expanding stent imparts on the vascular wall at the endothelial surface, the underlying plaque lesions and other tissue components during expansion is an important step in improving short term stent-wall mechanics. More importantly, the long term influence of stent-vascular wall mechanical interactions in restenosis remains unknown, and this analysis may shed light on the process.Copyright © 2007 by ASME

To study the interaction between a stone and a cavitation jet during extracorporeal shock-wave lithotripsy (ESWL), we developed a model based on geometrical acoustics describing the impingement of a cavitation microjet on an elastic solid boundary and the subsequent propagation of the resultant shock waves in the solid. The model incorporated the acoustic and mechanical properties of different stone types to calculate the jet impact pressure at the stone surface and the stress and strain at the propagating shock fronts. This model was validated using stone phantoms in slab configuration fabricated to have comparable acoustic and mechanical properties to renal calculi. This chapter summarizes our efforts, both analytical and experimental, towards the understanding of stone fragmentation in extracorporeal shock wave lithotripsy.

An in vitro force measurement assay has been developed to quantify the forces exerted by single corneal fibroblasts during the early interaction with a collagen matrix. Corneal fibroblasts were sparsely seeded on top of collagen matrices whose stiffness was predetermined by micromanipulation with calibrated fine glass microneedles. The forces exerted by individual cells were calculated from time-lapse videomicroscopic recordings of the 2-D elastic distortion of the matrix. In additional experiments, the degree of permanent reorganization of the collagen matrices was assessed by lysing the cells with 1% Triton X-100 solution at the end of a 2-hour incubation and recording the subsequent relaxation. The data suggest that a cell can exert comparable centripetal force during either extension of a cell process or partial retraction of an extended pseudopodia. The rates of force associated with pseudopodial extension and partial retraction were 0.180 +/- 0.091 (x 10(-8)) N/min (n = 8 experiments) and 0.213 +/- 0.063 (x 10(-8)) N/min (n = 8 experiments), respectively. Rupture of pseudopodial adhesion associated with cell locomotion causes a release of force on the matrix and a complete recoil of the pseudopodia concerned; a simultaneous release of force on the matrix was also observed at the opposite end of the cell. Lysis of cells resulted in 84 +/- 18% relaxation of the matrix, suggesting that little permanent remodeling of matrix is produced by the actions of isolated migrating cells.

Advances in tissue engineering have led to the development of artificially grown dermal tissues for use in burn and ulcer treatments. An example of such an engineered tissue is Dermagraft™, which is grown using human neonatal fibroblasts on rectangular sheets of biodegradable mesh. Using small angle light scattering (SALS), we quantified the collagen fiber architecture of Dermagraft with the mesh scaffold contributions removed through the use of a structurally based optical model. Dermagraft collagen fibers were found to have a preferred direction nearly parallel to the long dimension of the kiteshaped mesh opening with small spatial variations over the mesh. This study demonstrated the utility of SALS as a rapid and inexpensive technique for the evaluation of gross collagen fiber architecture in engineered tissues.

The biaxial mechanical properties of right ventricular free wall (RVFW) myocardium were studied. Tissue specimens were obtained from the sub-epicardium of potassium-arrested hearts and different stretch protocols were used to characterize the myocardium’s mechanical response. To assess regional differences, we excised tissue specimens from the conus and sinus regions. The RVFW myocardium was found to be consistently anisotropic, with a greater stiffness along the preferred (or averaged) fiber direction. The anisotropy in the conus region was more pronounced than in the sinus region. A comparison with studies of left ventricle (LV) midwall myocardium revealed that, 1) the fiber direction stiffnesses are greater in the RVFW than in the LV, 2) the degree of anisotropy is greater in the RVFW than in the LV.

We used biplane cinefluorgraphy to study the regional deformation and local contractile function of the canine right ventricular free wall (RVFW) among the inflow, midventricular, and outflow regions. For a region delimited by three neighboring markers, under the assumption of homogeneous deformation, we identified the magnitudes and directions of principal shortening or elongation and changes in area every 16.7 ms. Furthermore, we extended this approach to study the alterations of these parameters during RV afterload increase by applying pulmonary artery (PA) occlusion. Results show that, at both control and PA occlusion states, the outflow region was subjected to maximal fractional area reduction (AR) and maximal time rate of fractional area reduction (ARR) during systole, with no differences between inflow and midventricular regions (P less than 0.05). At the control state, the percent AR and the corresponding value for ARR were 27% and 179%/s at the outflow, 19% and 112%/s at the midventricular, and 15% and 107%/s at the inflow region, respectively. During PA occlusion, they became 21% and 115%/s at the outflow, 14% and 97%/s at the midventricular, and 15% and 102%/s at the inflow region, respectively. Statistically, only the outflow region deformation was affected by PA occlusion (P less than 0.05). For the control state, we also compared the direction of regional principal shortening at end systole to the local transmural myocardial fiber orientations. The directions were found to correspond closely to the mean of all local transmural fiber orientations. This suggests that the regional RVFW deformation we measured is the combined deformation behavior from all the local participating myofibers.