Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Dailey HL, Ricles LM, Yalcin HC, Ghadiali SN. Image-based finite element modeling of alveolar epithelial cell injury during airway reopening. J Appl Physiol 106: 221-232, 2009. First published November 13, 2008 doi:10.1152/japplphysiol.90688.2008.-The acute respiratory distress syndrome (ARDS) is characterized by fluid accumulation in small pulmonary airways. The reopening of these fluidfilled airways involves the propagation of an air-liquid interface that exerts injurious hydrodynamic stresses on the epithelial cells (EpC) lining the airway walls. Previous experimental studies have demonstrated that these hydrodynamic stresses may cause rupture of the plasma membrane (i.e., cell necrosis) and have postulated that cell morphology plays a role in cell death. However, direct experimental measurement of stress and strain within the cell is intractable, and limited data are available on the mechanical response (i.e., deformation) of the epithelium during airway reopening. The goal of this study is to use image-based finite element models of cell deformation during airway reopening to investigate how cell morphology and mechanics influence the risk of cell injury/necrosis. Confocal microscopy images of EpC in subconfluent and confluent monolayers were used to generate morphologically accurate three-dimensional finite element models. Hydrodynamic stresses on the cells were calculated from boundary element solutions of bubble propagation in a fluid-filled parallel-plate flow channel. Results indicate that for equivalent cell mechanical properties and hydrodynamic load conditions, subconfluent cells develop higher membrane strains than confluent cells. Strain magnitudes were also found to decrease with increasing stiffness of the cell and membrane/cortex region but were most sensitive to changes in the cell's interior stiffness. These models may be useful in identifying pharmacological treatments that mitigate cell injury during airway reopening by altering specific biomechanical properties of the EpC. flow-induced cell injury; epithelial cell mechanics; orthotropic membrane; ADINA CERTAIN PATHOLOGICAL CONDITIONS such as pneumonia and sepsis can lead to the development of the acute respiratory distress syndrome (ARDS), which is the most severe manifestation of acute lung injury (ALI). This condition is characterized by increased permeability of the alveolar-capillary barrier leading to fluid accumulation in the distal airways (43). In many cases, mechanical ventilation is necessary to stabilize patients with ARDS. However, ventilators can generate injurious mechanical forces that exacerbate the existing lung trauma. These mechanical forces, which are typically applied to lung epithelial cells (EpC), can cause cell necrosis (6, 46), further barrier disruption (9, 10, 46), and upregulation of inflammatory pathways (36). These mechanical and biological responses lead to additional lung injury known as ventilator-associated lung injury (VALI) (12). Although recent advances in ventilation protocols, including low tidal volu...

No abstract

No abstract

Solvent-cast 3D printing with peptide–polymer conjugates introduces a versatile platform to spatially organize peptides to guide local cell behavior.

The reopening of fluid-occluded pulmonary airways generates microbubble flows which impart complex hydrodynamic stresses to the epithelial cells lining airway walls. In this study we used boundary element solutions and finite element techniques to investigate how cell rheology influences the deformation and injury of cells during microbubble flows. An optimized Prony-Dirichlet series was used to model the cells' power-law rheology (PLR) and results were compared with a Maxwell fluid model. Results indicate that membrane strain and the risk for cell injury decreases with increasing channel height and bubble speed. In addition, the Maxwell and PLR models both indicate that increased viscous damping results in less cellular deformation/injury. However, only the PLR model was consistent with the experimental observation that cell injury is not a function of stress exposure duration. Correlation of our models with experimental observations therefore highlights the importance of using PLR in computational models of cell mechanics/deformation. These computational models also indicate that altering the cell's viscoelastic properties may be a clinically relevant way to mitigate microbubble-induced cell injury.

Quantitative assessment of bone fracture healing remains a significant challenge in orthopaedic trauma research. Accordingly, we developed a new technique for assessing bone healing using virtual mechano-structural analysis of computed tomography (CT) scans. CT scans from 19 fractured human tibiae at 12 weeks after surgery were segmented and prepared for finite element analysis (FEA). Boundary conditions were applied to the models to simulate a torsion test that is commonly used to access the structural integrity of long bones in animal models of fracture healing. The output of each model was the virtual torsional rigidity (VTR) of the healing zone, normalized to the torsional rigidity of each patient's virtually reconstructed tibia. This provided a structural measure to track the percentage of healing each patient had undergone. Callus morphometric measurements were also collected from the CT scans. Results showed that at 12 weeks post-op, more than 75% of patients achieved a normalized VTR (torsional rigidity relative to uninjured bone) of 85% or above. The predicted intact torsional rigidities compared well with published cadaveric data. Across all patients, callus volume and density were weakly and nonsignificantly correlated with normalized VTR and time to clinical union. Conversely, normalized VTR was significantly correlated with time to union (R 2 = 0.383, p = 0.005). This suggests that fracture scoring methods based on the visual appearance of callus may not accurately predict mechanical integrity. The image-based structural analysis presented here may be a useful technique for assessment of bone healing in orthopaedic trauma research.

Finite element analysis with models derived from computed tomography (CT) scans is potentially powerful as a translational research tool because it can achieve what animal studies and cadaver biomechanics cannot-low-risk, noninvasive, objective assessment of outcomes in living humans who have actually experienced the injury, or treatment being studied. The purpose of this study was to assess the validity of CT-based virtual mechanical testing with respect to physical biomechanical tests in a large animal model. Three different tibial osteotomy models were performed on 44 sheep. Data from 33 operated limbs and 20 intact limbs was retrospectively analyzed. Radiographic union scoring was performed on the operated limbs and physical torsional tests were performed on all limbs. Morphometric measures and finite element models were developed from CT scans and virtual torsional tests were performed to assess healing with four material assignment techniques. In correlation analysis, morphometric measures and radiographic scores were unreliable predictors of biomechanical rigidity, while the virtual torsion test results were strongly and significantly correlated with measured biomechanical test data, with high absolute agreement. Overall, the results validated the use of virtual mechanical testing as a reliable in vivo assessment of structural bone healing. This method is readily translatable to clinical evaluation for noninvasive assessment of the healing progress of fractures with minimal risk. Clinical significance: virtual mechanical testing can be used to reliably and noninvasively assess the rigidity of a healing fracture using clinical-resolution CT scans and that this measure is superior to morphometric and radiographic measures.