Background-Growing evidence suggests that intramyocardial biomaterial injection improves cardiac functions after myocardial infarction (MI) in rodents. Cell therapy is another promising approach to treat MI, although poor retention of transplanted cells is a major challenge. In this study, we hypothesized that intramyocardial injection of self-assembling peptide nanofibers (NFs) thickens the infarcted myocardium and increases transplanted autologous bone marrow mononuclear cell (MNC) retention to attenuate cardiac remodeling and dysfunction in a pig MI model. Methods and Results-A total of 40 mature minipigs were divided into 5 groups: sham, MIϩnormal saline, MIϩNFs, MIϩMNCs, and MIϩMNCs/NFs. MI was induced by coronary occlusion followed by intramyocardial injection of 2 mL normal saline or 1% NFs with or without 1ϫ10 8 isolated autologous MNCs. NF injection significantly improved diastolic function and reduced ventricular remodeling 28 days after treatment. Injection of MNCs alone ameliorated systolic function only, whereas injection of MNCs with NFs significantly improved both systolic and diastolic functions as indicated by ϩdP/dt and ϪdP/dt (1214.5Ϯ91.9 and Ϫ1109.7Ϯ91.2 mm Hg/s in MIϩNS, 1693.7Ϯ84.7 and Ϫ1809.6Ϯ264.3 mm Hg/s in MIϩMNCs/NFs, respectively), increased transplanted cell retention (29.3Ϯ4.5 cells/mm 2 in MIϩMNCs and 229.4Ϯ41.4 cells/mm 2 in MIϩMNCs/NFs) and promoted capillary density in the peri-infarct area. Conclusions-We demonstrated that NF injection alone prevents ventricular remodeling, whereas cell implantation withNFs improves cell retention and cardiac functions after MI in pigs. This unprecedented combined treatment in a large animal model has therapeutic effects, which can be translated to clinical applications in the foreseeable future. (Circulation. 2010; 122[suppl 1]:S132-S141.)Key Words: biomaterials Ⅲ bone marrow mononuclear cells Ⅲ cardiac tissue engineering Ⅲ myocardial infarction C ongestive heart failure is a leading cause of death in the United States and other developed countries. The dominant cause of heart failure is loss of myocardium due to coronary artery disease and the limited regeneration potential of cardiomyocytes. Cardiac tissue engineering is a promising and actively developing area of research aiming to repair, replace, and regenerate the myocardium. Several studies have demonstrated the feasibility of this approach and indicated that direct injection of biomaterials into the infarcted myocardium may be beneficial in preventing deleterious remodeling and reducing cardiac dysfunction. [1][2][3][4] Previous studies using intramyocardial injection of self-assembling peptide nanofibers (NFs), a highly biocompatible 5,6 and biodegradable 7 material, have also revealed their therapeutic potentials for angiogenesis, controlled drug/growth factor release, cell delivery, and stem cell recruitment. [5][6][7][8][9][10] These results indicate that NFs may impact a broad spectrum of applications in myocardial tissue engineering.Cell therapy is another promising approach to h...

Results of calculations and experiments on the flow of a viscous liquid through an axisymmetric conduit expansion are reported. The streamlines and vorticity contours are presented as functions of the Reynolds number of the flow. The dynamic interaction between the main flow and the captive eddy between it and the walls is analysed, and it is concluded that, for laminar flow, the main role of the eddy is that of shaping the flow with a rather small energy exchange.

An implicit finite-difference technique employing orthogonal curvilinear co-ordinates is used to solve the Navier–Stokes equations for peristaltic flows in which both the wall-wave curvature and the Reynolds number are finite (§2). The numerical solutions agree closely with experimental flow visualizations. The kinematic characteristics of both extensible and inextensible walls (§3) are found to have a distinct influence on the flow processes only near the wall. Without vorticity, peristaltic flow observed from a reference frame moving with the wave will be equivalent to steady potential flow through a stationary wavy channel of similar geometry (§4). Solutions for steady viscous flow (§5) are obtained from simulation of unsteady flow processes beginning from an initial condition of potential peristaltic flow. For nonlinear flows due to a single peristaltic wave of dilatation, the highest stresses and energy exchange rates (§6) occur along the wall and in two instantaneous stagnation regions in the bolus core. A series of computations for periodic wave trains reveals that increasing the Reynolds number from 2[sdot ]3 to 251 yields a modest augmentation in the ratio of flow rate to Reynolds number but induces a much greater increase in the shear stress (§7.1). The transport effectiveness is markedly reduced for pumping against a mild adverse pressure drop (§7.2). Increasing the wave amplitude will lead to the development of travelling vortices within the core region of the peristaltic flow (§7.3).

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Some insight into the mechanism of solid-particle transport by peristalsis is sought experimentally through a two-dimensional model study (§ 2). The peristaltic wave is characterized by a single bolus sweeping by the particle, resulting in oscillatory motion of the particle. Because of fluid-particle interaction and the significant curvature in the wall wave, the peristaltic flow is highly nonlinear and time dependent.For a neutrally buoyant particle propelled along the axis of the channel by a single bolus, the net particle displacement can be either positive or negative. The instantaneous force acting upon the particle and the resultant particle trajectory are sensitive to the Reynolds number of the flow (§ 3 and 4). The net forward movement of the particle increases slightly with the particle size but decreases rapidly as the gap width of the bolus increases. The combined dynamic effects of the gap width and Reynolds number on the particle displacement are studied (§ 5). Changes in both the amplitude and the form of the wave have significant effects on particle motion. A decrease in wave amplitude along with an increase in wave speed may lead to a net retrograde particle motion (§ 6). For a non-neutrally buoyant particle, the gravitational effects on particle transport are modelled according to the ratio of the Froude number to the Reynolds number. The interaction of the particle with the wall for this case is also explored (§ 7).When the centre of the particle is off the longitudinal axis, the particle will undergo rotation as well as translation. Lateral migration of the particle is found to occur in the curvilinear flow region of the bolus, leading to a reduction in the net longitudinal transport (§ 8). The interaction of the curvilinear flow field with the particle is further discussed through comparison of flow patterns around a particle with the corresponding cases without a particle (§ 9).

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An in-vivo experimental technique was employed to determine the linear and nonlinear characteristics of viscoelastic properties of the spinal cord of anesthetized cats. The stress relaxation and recovery curves were reproducible in a group of cat experiments. The data of linear viscoelastic properties were used to develop a power law model with Boltzmann's convolution integral. The model was capable of predicting a prolonged stress relaxation and recovery curve. For larger deformation, the results were quantified using a nonlinear analysis of viscoelastic response of the spinal cord under the uniaxial experiment.