We developed a live imaging system enabling dynamic visualization of single cell alignment induced by external mechanical force in a 3-D collagen matrix. The alignment dynamics and migration of smooth muscle cells (SMCs) were studied by time lapse differential interference contrast and /or phase contrast microscopy. Fluorescent and reflection confocal microcopy were used to study the SMC morphology and the microscale collagen matrix remodeling induced by SMCs. A custom developed program was used to quantify the cell migration and matrix remodeling. Our system enables cell concentration-independent alignment eliminating cell-to-cell interference and enables dynamic cell tracking, high magnification observation and rapid cell alignment accomplished in a few hours compared to days in traditional models. We observed that cells sense and response to the mechanical signal before cell spreading. Under mechanical stretch the migration directionality index of SMCs is 46.3% more than those cells without external stretch; the dynamic direction of cell protrusion is aligned to that of the mechanical force; SMCs showed directional matrix remodeling and the alignment index calculated from the matrix in front of cell protrusions is about 3 fold of that adjacent to cell bodies. Our results indicate that the mechanism of cell alignment is directional cell protrusion. Mechano-sensing, directionality in cell protrusion dynamics, cell migration and matrix remodeling are highly integrated. Our system provides a platform for studying the role of mechanical force on the cell matrix interactions and thus find strategies to optimize selected properties of engineered tissues.
Many rat/mouse pressure ulcer (PU) models have been developed to test different hypotheses to gain deeper understanding of various causative risk factors, the progress of PUs, and assessing effectiveness of potential treatment modalities. The recently emphasized deep tissue injury (DTI) mechanisms for PU formation has received increased attention and several studies reported findings on newly developed DTI animal models. However, concerns exist for the clinical relevance and validity of these models, especially when the majority of the reported rat PU/DTI models were not built upon SCI animals and many of the DTI research did not simulate well the clinical observation. In this study, we propose a rat PU and DTI model which is more clinically relevant by including chronic SCI condition into the rat PU model and to simulate the role of bony prominence in DTI formation by using an implant on the bone-tissue interface. Histological data and imaging findings confirmed that the condition of chronic SCI had significant effect on pressure-induced tissue injury in a rat PU model and the including a simulated bony prominence in rat DTI model resulted in significantly greater injury in deep muscle tissue. Further integration of the SCI condition and the simulated bony prominence would result a rat PU/DTI model which can simulate even more accurately the clinical phenomenon and yield research more clinically relevant findings.
Hydraulic fracturing in unconsolidated or poorly consolidated formations has been used as a technique for well stimulation and for sand control. Although a large number of hydraulic fracturing operations have been performed in soft formations, the exact mechanisms of failure and fracture propagation remain an unresolved issue. Conventional hydraulic fracturing models based on the theory of linear elastic fracture mechanics (LEFM) often lead to inaccurate results because large inelastic deformations and strong fluid-solid coupling are neglected in such models.
A fully three-dimensional hydraulic fracture growth model for soft sands is developed. Our model can simulate non-planar fracture growth in poro-elasto-plastic materials, fluid flow inside the fracture with proppant transport, and fluid leak-off from the fracture to the porous reservoir. This paper presents the formulation and implementation of a new model. The model is verified by comparisons with analytical solutions. The model predicts considerably higher net fracturing pressure due to plasticity, which is consistent with observations from the field and laboratory experiments. This is because the stress concentrations at the crack tip in a plastic material are lower than in an elastic material and the plastic yielding shields the tip from the fracturing pressure. This induces shorter and wider fractures than without plasticity. Also, fluid leak-off and the pore pressure diffusion in the reservoir are computed numerically in this model. Higher leak-off leads to a poroelastic backstress that builds up around the fracture and results in shorter fractures.
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