A poroelastic model describing nutrient transport and cell stresses within a cyclically strained collagen hydrogel.

In the creation of engineered tissue constructs, the successful transport of nutrients and oxygen to the contained cells is a significant challenge. In highly porous scaffolds subject to cyclic strain, the mechanical deformations can induce substantial fluid pressure gradients, which affect the transport of solutes. In this article, we describe a poroelastic model to predict the solid and fluid mechanics of a highly porous hydrogel subject to cyclic strain. The model was validated by matching the predicted penetration of a bead into the hydrogel from the model with experimental observations and provides insight into nutrient transport. Additionally, the model provides estimates of the wall-shear stresses experienced by the cells embedded within the scaffold. These results provide insight into the mechanics of and convective nutrient transport within a cyclically strained hydrogel, which could lead to the improved design of engineered tissues.

The influence of fluid flow on modeling quorum sensing in bacterial biofilms.

In this paper, we study quorum sensing in Pseudomonas aeruginosa biofilms. Quorum sensing is a process where bacteria monitor their population density through the release of extra-cellular signalling molecules. The presence of these molecules affects gene modulation leading to changes in behaviour such as the release of virulence factors. Here, we use numerical methods to approximate a 2-D model of quorum sensing. It is observed that the shape of the biofilm can have a profound effect on the onset of quorum sensing. This has serious repercussions for experimental observations since biofilms of the same biomass but different shapes can produce quite different results.

Mathematical Model for Computer-Assisted Modification of Medication Dosing Rules.

OBJECTIVE: Medication dosing in pediatrics is complex and prone to errors that may lead to patient harm. To improve computer-assisted dosing, a mathematical model and algorithm were developed to optimize clinical decision support dosing rules and reduce spurious alerts. The objective was to evaluate the feasibility of using this algorithm to adjust dosing rules. MATERIALS AND METHODS: Incorporating historical ordering data, a mathematical model and algorithm were developed to automatically determine optimal dosing rule parameters. The algorithm optimizes the dosing rules by balancing the number of alerts generated for a medication with a minimal length dose interval. In all, 5 candidate medications were tested. An analysis was performed to compare the number of alerts generated by the new model with the current dosing rules. RESULTS: For the 5 medications, the algorithm generated multiple clinically relevant rule possibilities and the rules returned performed as well as current dosing rule or matched historical prescriber behavior. The rules were comparable to or better than the existing system rules in reducing the total alert burden. DISCUSSION: The mathematical model and algorithm are an accurate and scalable solution to adjusting medication dosing rules. They can be implemented to change suboptimal rules more quickly than current manual methods and can be used to help identify and correct poor quality rules. CONCLUSIONS: Mathematical modeling using historic prescribing data can generate clinically appropriate electronic dosing rule parameters. This approach represents an automatable and scalable solution that could help reduce alert fatigue and decrease medication dosing errors.

Trapping of embolic particles in a vessel phantom by cavitation-enhanced acoustic streaming.

Cavitation clouds generated by short, high-amplitude, focused ultrasound pulses were previously observed to attract, trap, and erode thrombus fragments in a vessel phantom. This phenomenon may offer a noninvasive method to capture and eliminate embolic fragments flowing through the bloodstream during a cardiovascular intervention. In this article, the mechanism of embolus trapping was explored by particle image velocimetry (PIV). PIV was used to examine the fluid streaming patterns generated by ultrasound in a vessel phantom with and without crossflow of blood-mimicking fluid. Cavitation enhanced streaming, which generated fluid vortices adjacent to the focus. The focal streaming velocity, uf, was as high as 120 cm/s, while mean crossflow velocities, uc, were imposed up to 14 cm/s. When a solid particle 3-4 mm diameter was introduced into crossflow, it was trapped near the focus. Increasing uf promoted particle trapping while increasing uc promoted particle escape. The maximum crossflow Reynolds number at which particles could be trapped, Rec, was approximately linear with focal streaming number, Ref, i.e. Rec = 0.25Ref + 67.44 (R(2) = 0.76) corresponding to dimensional velocities uc = 0.084uf + 3.122 for 20 < uf < 120 cm/s. The fluidic pressure map was estimated from PIV and indicated a negative pressure gradient towards the focus, trapping the embolus near this location.

A mechanochemical model of striae distensae.

Striae distensae, otherwise known as stretch marks, are common skin lesions found in a variety of clinical settings. They occur frequently during adolescence or pregnancy where there is rapid tissue expansion and in clinical situations associated with corticosteroid excess. Heralding their onset is the appearance of parallel inflammatory streaks aligned perpendicular to the direction of skin tension. Despite a considerable amount of investigative research, the pathogenesis of striae remains obscure. The interpretation of histologic samples - the major investigative tool - demonstrates an association between dermal lymphocytic inflammation, elastolysis, and a scarring response. Yet the primary causal factor in their aetiology is mechanical; either skin stretching due to underlying tissue expansion or, less frequently, a compromised dermis affected by normal loads. In this paper, we investigate the pathogenesis of striae by addressing the coupling between mechanical forces and dermal pathology. We develop a mathematical model that incorporates the mechanical properties of cutaneous fibroblasts and dermal extracellular matrix. By using linear stability analysis and numerical simulations of our governing nonlinear equations, we show that this quantitative approach may provide a realistic framework that may account for the initiating events.

Combination of fluid and solid mechanical stresses contribute to cell death and detachment in a microfluidic alveolar model.

Studies using this micro-system demonstrated significant morphological differences between alveolar epithelial cells (transformed human alveolar epithelial cell line, A549 and primary murine alveolar epithelial cells, AECs) exposed to combination of solid mechanical and surface-tension stresses (cyclic propagation of air-liquid interface and wall stretch) compared to cell populations exposed solely to cyclic stretch. We have also measured significant differences in both cell death and cell detachment rates in cell monolayers experiencing combination of stresses. This research describes new tools for studying the combined effects of fluid mechanical and solid mechanical stress on alveolar cells. It also highlights the role that surface tension forces may play in the development of clinical pathology, especially under conditions of surfactant dysfunction. The results support the need for further research and improved understanding on techniques to reduce and eliminate fluid stresses in clinical settings.