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Intracellular calcium oscillation caused by receptor activator of nuclear factor kappa-B ligand has been demonstrated to promote the differentiation of osteoclasts. Osteoclasts are recruited on the surface of trabeculae, and are exposed to fluid flow caused by the deformation of the bone matrix. However, the roles of fluid shear stress (FSS) on calcium response during the differentiation process of osteoclasts are still unknown. In the current study, the formation of tartrate-resistant acid phosphatase-positive, multinucleated osteoclasts from RAW264.7 macrophage cells were induced by co-culturing them with the conditioned medium from MC3T3-E1 osteoblasts. The in situ observations showed a high correlation between the area and the nuclear number of osteoclasts. The cells were stimulated by FSS at different levels (1 or 10 dyne/cm2) before (0 day) or after being induced for 4 or 8 days. The mechanically-induced calcium response was recorded and analyzed. The results indicated a different property of calcium oscillation for the osteoclasts in different fusion stages (i.e., more calcium-responsive peaks appeared in small osteoclasts than those in the larger ones). The rates of calcium influx decreased and the time of recovery in osteoclast cytosol increased along with the fusion of osteoclasts. In addition, increasing the FSS level enhanced the calcium oscillation of osteoclasts at early induction (4 days). However, this effect was weakened at the late induction (8 days). The present work could help provide understanding regarding the mechanism of the involvement of calcium in mechanically induced bone remodeling.

Understanding the effect of cold storage on arterial tissues is essential in various clinical and experimental practices. Cold storage techniques could significantly affect the post-cryosurgical or post-cryopreservation mechanical behavior of arteries. Previously, arteries were considered homogenous and elastic and the changes in material properties due to cold storage were inconclusive. In this study, using a custom-made nanoindentation device, changes to the local viscoelastic properties of porcine thoracic aorta wall due to three common storage temperatures (+4, −20, and −80 °C) within 24 h, 48 h, 1 week, and 3 weeks were characterized. The changes to both elastic and relaxation behaviors were investigated considering the multilayer, heterogeneous nature of the aortic wall. The results showed that the average instantaneous Young’s modulus (E) of +4 °C storage samples decreased while their permanent average relaxation amplitude (G ∞) increased and after 48 h these changes became significant (10 and 13% for E and G ∞, respectively). Generally, in freezer storage, E increased and G ∞ showed no significant change. In prolonged preservation (>1 week), the results of −20 °C showed significant increase in E (20% after 3 weeks) while this increase for −80 °C was not significant, making it a better choice for tissue cold storage applications.

The induction of angiogenesis is a promising therapeutic strategy for the amelioration of peripheral arterial disease (PAD). This occlusive disease results in muscle ischemia, and neovascularization is a route to increasing the perfusion in the tissue. The vascular endothelial growth factor (VEGF) family of potent pro-angiogenic cytokines is a potential therapeutic agent, increasing VEGF-receptor signaling on tissue vasculature. To investigate the effects of possible therapies on the VEGF concentrations and gradients within the tissue, we consider three such strategies: VEGF gene therapy (e.g. by adeno-associated virus); VEGF cell-based therapy (injected myoblasts that overexpress VEGF); and chronic exercise (which upregulates VEGF receptor expression). The multi-scale computational model used to investigate these strategies is an integration of several components: an anatomical description of the muscle geometry and cell types; microvascular blood flow; tissue oxygen distribution; VEGF secretion from muscle fibers; VEGF transport through interstitial space; and VEGF-receptor binding on microvascular endothelial cells. Exercise training, which results in increased VEGF secretion in hypoxic tissue and increased VEGF receptor expression, exhibits increases in both VEGF concentration and VEGF gradients, and is predicted to be more effective than the other, VEGF-only treatments.

Transmural variations in the relationship between structural and fluid transport properties of myocardial capillary networks are determined via continuum modeling approaches using recent three-dimensional (3D) data on the microvascular structure. Specifically, the permeability tensor, which quantifies the inverse of the blood flow resistivity of the capillary network, is computed by volume-averaging flow solutions in synthetic networks with geometrical and topological properties derived from an anatomically-detailed microvascular data set extracted from the rat myocardium. Results show that the permeability is approximately ten times higher in the principal direction of capillary alignment (the “longitudinal” direction) than perpendicular to this direction, reflecting the strong anisotropy of the microvascular network. Additionally, a 30% increase in capillary diameter from subepicardium to subendocardium is shown to translate to a 130% transmural rise in permeability in the longitudinal capillary direction. This result supports the hypothesis that perfusion is preferentially facilitated during diastole in the subendocardial microvasculature to compensate for the severely-reduced systolic perfusion in the subendocardium.

A three-dimensional model is developed in this study to examine the transient and steady state temperature distribution in the brain during selective brain cooling (SBC) and subsequent rewarming. Selective brain cooling is induced through either wearing a cooling helmet or packing the head with ice. The ischemic region of the brain is simulated through reducing the blood perfusion rate to 20% of its normal value. The geometric and thermal properties and physiological characteristics for each layer, as well as the arterial blood temperature, are used as the input to the Pennes bioheat equation. Our data suggest that rapid cooling of the brain gray matter can be achieved by SBC on the head surface (26 min for adults versus 15 min for infants). Suboptimal thermal contact between the head surface and the coolant in most commercially available cooling helmets is suspected to be the main reason for delayed cooling in SBC as compared to the ice packing. The study has also demonstrated that the simulated 3 °C/h passive rewarming rate by exposing the head to room temperature after removing the source of cooling may be too rapid. © 2003 Biomedical Engineering Society. PAC2003: 8710+e, 8719La, 8719Pp, 8719Uv

Cardiac tissue conductivity measurements can be used to assess the electrical substrate underlying normal and abnormal wavefront propagation. We describe a method of solving the inverse cardiac bidomain model to estimate average longitudinal and transverse intra and extra-cellular conductivities and fiber angle relative to an electrode array placed arbitrarily on the epi- or endocardial surface. A Newton–Raphson reconstruction method and two Tikhonov-type regularizations were able to stably identify conductivities and fiber angles in tissue models having anisotropies similar to those in real cardiac tissue. The reconstruction methods were tested with data from increasingly realistic two dimensional cardiac bidomain models and performed well both when measurement noise was added, and when simulated experimental and forward model matching was diminished. This approach may be a suitable basis for continuous monitoring of myocardial condition in-vivo via a catheter based electrode array.

Neural prosthetic devices hold the potential to be used in the treatment of a variety of neurological disorders. However, their long-term clinical success is currently limited by the ability to achieve stable interfaces between devices and the CNS. Immunohistochemical analysis has shown that cellular responses occur in tissue surrounding implanted devices. These cellular responses have been correlated with the impedance measured from device electrodes, leading to the hypothesis that a possible mechanism resulting in inconsistent device performance is the formation of an electrically insulating glial sheath at the implantation site. However, little is known about what cellular and tissue changes affect impedance values and thus contribute to the decreases in electrode performance. We have designed an in vitro system in which cell conditions can be varied within an artificial tissue matrix surrounding a neural prosthetic device. In this study, high-density cultures of glial cells were analyzed by immunohistochemical methods and impedance spectroscopy. Astrocytes and microglia were cultured at various ratios within the matrix surrounding the probes, and were observed over a period of 2 weeks. Cell seeding conditions and confocal images were compared to impedance data to enable the effects of glial cell type on electrode impedance to be determined.

Blood flow to perfuse the muscle cells of the heart is distributed by the capillary blood vessels via the coronary arterial tree. Because the branching pattern and vascular geometry of the coronary vessels in the ventricles and atria are nonuniform, the flow in all of the coronary capillary blood vessels is not the same. This nonuniformity of perfusion has obvious physiological meaning, and must depend on the anatomy and branching pattern of the arterial tree. In this study, the statistical distribution of blood pressure, blood flow, and blood volume in all branches of the coronary arterial tree is determined based on the anatomical branching pattern of the coronary arterial tree and the statistical data on the lengths and diameters of the blood vessels. Spatial nonuniformity of the flow field is represented by dispersions of various quantities (SD/mean) that are determined as functions of the order numbers of the blood vessels. In the determination, we used a new, complete set of statistical data on the branching pattern and vascular geometry of the coronary arterial trees. We wrote hemodynamic equations for flow in every vessel and every node of a circuit, and solved them numerically. The results of two circuits are compared: oneasymmetric model satisfies all anatomical data (including the meanconnectivity matrix) and the other, asymmetric model, satisfies all mean anatomical data except the connectivity matrix. It was found that the mean longitudinal pressure drop profile as functions of the vessel order numbers are similar in both models, but the asymmetric model yields interesting dispersion profiles of blood pressure and blood flow. Mathematical modeling of the anatomy and hemodynamics is illustrated with discussions on its accuracy.