Hypoplastic left heart syndrome is the most common lethal cardiac malformation of the newborn. Its treatment, apart from heart transplantation, is the Norwood operation. The initial procedure for this staged repair consists of reconstructing a circulation where a single outlet from the heart provides systemic perfusion and an interpositioning shunt contributes blood flow to the lungs. To better understand this unique physiology, a computational model of the Norwood circulation was constructed on the basis of compartmental analysis. Influences of shunt diameter, systemic and pulmonary vascular resistance, and heart rate on the cardiovascular dynamics and oxygenation were studied. Simulations showed that 1) larger shunts diverted an increased proportion of cardiac output to the lungs, away from systemic perfusion, resulting in poorer O2 delivery, 2) systemic vascular resistance exerted more effect on hemodynamics than pulmonary vascular resistance, 3) systemic arterial oxygenation was minimally influenced by heart rate changes, 4) there was a better correlation between venous O2 saturation and O2 delivery than between arterial O2 saturation and O2 delivery, and 5) a pulmonary-to-systemic blood flow ratio of 1 resulted in optimal O2 delivery in all physiological states and shunt sizes.

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Computational fluid dynamic methods based on a finite-element technique were applied to the study of (1) competition of flows in the inferior and superior venae cavae in total cavopulmonary connection, and (2) competition between flow in the superior vena cava and forward flow from a stenosed pulmonary artery in bidirectional cavopulmonary anastomosis. Models corresponding to various degrees of offsetting and shape of the inferior vena caval anastomosis were simulated to evaluate energy dissipation and flow distribution between the two lungs. A minimal energy loss with optimal flow distribution between the two lungs was obtained by enlarging the inferior vena caval anastomosis toward the right pulmonary artery. This modified technique of total cavopulmonary connection is described. A computational model of the operation was developed in an attempt to understand the mechanisms of postoperative failure. In tight pulmonary artery stenosis (75%), the pulsatile forward flow is primarily directed to the left pulmonary artery, with little influence on superior vena caval pressure and the right pulmonary artery. Pulsatile forward flows corresponding to 15%, 30%, 45%, and 60% of the systemic artery output increased the mean pulmonary artery and superior vena caval pressures by 1, 1.7, 2.4, and 3.6 mm Hg, respectively. Although the modeling studies were not able to determine the cause of postoperative failure, they emphasize the impact of local geometry on flow dynamics. More simulations are required for further investigation of the problem.

The control of stem cell response in vitro, including self-renewal and lineage commitment, has been proved to be directed by mechanical cues, even in the absence of biochemical stimuli. Through integrin-mediated focal adhesions, cells are able to anchor onto the underlying substrate, sense the surrounding microenvironment, and react to its properties. Substrate-cell and cell-cell interactions activate specific mechanotransduction pathways that regulate stem cell fate. Mechanical factors, including substrate stiffness, surface nanotopography, microgeometry, and extracellular forces can all have significant influence on regulating stem cell activities. In this paper, we review all the most recent literature on the effect of purely mechanical cues on stem cell response, and we introduce the concept of “force isotropy” relevant to cytoskeletal forces and relevant to extracellular loads acting on cells, to provide an interpretation of how the effects of insoluble biophysical signals can be used to direct stem cells fate in vitro.

Introduction: The effect of scaffold pore size and interconnectivity is undoubtedly a crucial factor for most tissue engineering applications. The aim of this study was to examine the effect of pore size and porosity on cartilage construct development in different scaffolds seeded with articular chondrocytes. Methods: We fabricated poly-L-lactide-co-trimethylene carbonate scaffolds with different pore sizes, using a solvent-casting/particulate-leaching technique. We seeded primary bovine articular chondrocytes on these scaffolds, cultured the constructs for 2 weeks and examined cell proliferation, viability and cell-specific production of cartilaginous extracellular matrix proteins, including GAG and collagen. Results: Cell density significantly increased up to 50% with scaffold pore size and porosity, likely facilitated by cell spreading on the internal surface of bigger pores, and by increased mass transport of gases and nutrients to cells, and catabolite removal from cells, allowed by lower diffusion barriers in scaffolds with a higher porosity. However, both the cell metabolic activity and the synthesis of cartilaginous matrix proteins significantly decreased by up to 40% with pore size. We propose that the association of smaller pore diameters, causing 3-dimensional cell aggregation, to a lower oxygenation caused by a lower porosity, could have been the condition that increased the cell-specific synthesis of cartilaginous matrix proteins in the scaffold with the smallest pores and the lowest porosity among those tested. Conclusions: In the initial steps of in vitro cartilage engineering, the combination of small scaffold pores and low porosity is an effective strategy with regard to the promotion of chondrogenesis