Patrick McGarry

Review on Cell Mechanics: Experimental and Modeling Approaches

The interplay between the mechanical properties of cells and the forces that they produce internally or that are externally applied to them play an important role in maintaining the normal function of cells. These forces also have a significant effect on the progression of mechanically related diseases. To study the mechanics of cells, a wide variety of tools have been adapted from the physical sciences. These tools have helped to elucidate the mechanical properties of cells, the nature of cellular forces, and mechanoresponses that cells have to external forces, i.e., mechanotransduction. Information gained from these studies has been utilized in computational models that address cell mechanics as a collection of biomechanical and biochemical processes. These models have been advantageous in explaining experimental observations by providing a framework of underlying cellular mechanisms. They have also enabled predictive, in silico studies, which would otherwise be difficult or impossible to perform with current experimental approaches. In this review, we discuss these novel, experimental approaches and accompanying computational models. We also outline future directions to advance the field of cell mechanics. In particular, we devote our attention to the use of microposts for experiments with cells and a bio-chemical-mechanical model for capturing their unique mechanobiological properties. [DOI: 10.1115/1.4025355]

Investigation of metallic and carbon fibre PEEK fracture fixation devices for three-part proximal humeral fractures

A computational investigation of proximal humeral fracture fixation has been conducted. Four devices were selected for the study; a locking plate, intramedullary nail (IM Nail), K-wires and a Bilboquet device. A 3D model of a humerus was created using a process of thresholding based on the grayscale values of a CT scan of an intact humerus. An idealised three part fracture was created in addition to removing a standard volume from the humeral head as a representation of bone voids that occur as a result of the injury. All finite element simulations conducted represent 90° arm abduction. Simulations were conducted to investigate the effect of filling this bone void with calcium phosphate cement for each device. The effect of constructing devices from carbon fibre polyetheretherketone (CFPEEK) was investigated. Simulations of cement reinforced devices predict greater stability for each device. The average unreinforced fracture line opening (FLO) is reduced by 48.5% for metallic devices with a lesser effect on composite devices with FLO reduced by 23.6%. Relative sliding (shear displacement) is also reduced between fracture fragments by an average of 58.34%. CFPEEK device simulations predict reduced stresses at the device-bone interface.

On anisotropic elasticity and questions concerning its Finite Element implementation

We give conditions on the strain–energy function of nonlinear anisotropic hyperelastic materials that ensure compatibility with the classical linear theories of anisotropic elasticity. We uncover the limitations associated with the volumetric–deviatoric separation of the strain–energy used, for example, in many Finite Element (FE) codes in that it does not fully represent the behavior of anisotropic materials in the linear regime. This limitation has important consequences. We show that, in the small deformation regime, a FE code based on the volumetric–deviatoric separation assumption predicts that a sphere made of a compressible anisotropic material deforms into another sphere under hydrostatic pressure loading, instead of the expected ellipsoid. For finite deformations, the commonly adopted assumption that fibres cannot support compression is incorrectly implemented in current FE codes and leads to the unphysical result that under hydrostatic tension a sphere of compressible anisotropic material deforms into a larger sphere.

Analysis of the Mechanical Behavior of a Titanium Scaffold With a Repeating Unit-Cell Substructure

Titanium scaffolds with controlled microarchitecture have been developed for load bearing orthopedic applications. The controlled microarchitecture refers to a repeating array of unit-cells, composed of sintered titanium powder, which make up the scaffold structure. The objective of this current research was to characterize the mechanical performance of three scaffolds with increasing porosity, using finite element analysis (FEA) and to compare the results with experimental data. Scaffolds were scanned using microcomputed tomography and FEA models were generated from the resulting computer models. Macroscale and unit-cell models of the scaffolds were created. The material properties of the sintered titanium powders were first evaluated in mechanical tests and the data used in the FEA. The macroscale and unit-cell FEA models proved to be a good predictor of Youngs modulus and yield strength. Although macroscale models showed similar failure patterns and an expected trend in UCS, strain at UCS did not compare well with experimental data. Since a rapid prototyping method was used to create the scaffolds, the original CAD geometries of the scaffold were also evaluated using FEA but they did not reflect the mechanical properties of the physical scaffolds. This indicates that at present, determining the actual geometry of the scaffold through computed tomography imaging is important. Finally, a fatigue analysis was performed on the scaffold to simulate the loading conditions it would experience as a spinal interbody fusion device.

Anisotropic mode-dependent damage of cortical bone using the extended finite element method (XFEM).

Anisotropic damage initiation criteria were developed for extended finite element method (XFEM) prediction of crack initiation and propagation in cortical bone. This anisotropic damage model was shown to accurately predict the dependence of crack propagation patterns and fracture toughness on mode mixity and on osteon orientations, as observed experimentally. Four initiation criteria were developed to define crack trajectories relative to osteon orientations and max principal stress for single and mixed mode fracture. Alternate failure strengths for tensile and compressive loading were defined to simulate the asymmetric failure of cortical bone. The dependence of cortical bone elasticity and failure properties on osteon orientation is analogous to the dependence of composite properties on fibre orientation. Hence, three of the criteria developed in the present study were based upon the Hashin damage criteria. The fourth criterion developed was defined in terms of the max principal stress. This criterion initiated off axis crack growth perpendicular to the direction of the max principal stress. The unique set of parameters calibrated accurately predicted; (i) the relationship between fracture energy and osteon alignment, (ii) the alternate crack patterns for both varying osteon orientations and loading angle. Application of the developed anisotropic damage models to cortical bone screw pullout highlights the potential application for orthopaedic device design evaluation.

Effect of calcium triphosphate cement on proximal humeral fracture osteosynthesis: a finite element analysis

Purpose. To measure the effect of void-filling calcium triphosphate cement on the loads at the implant-bone interface of a proximal humeral fracture osteosynthesis using a finite element analysis. Methods. Finite element models of a 3-part proximal humeral fracture fixed with a plate with and without calcium triphosphate cement augmentation were generated from a quantitative computed tomography dataset of an intact proximal humerus. Material properties were assigned to bone fragments using published expressions relating Youngs modulus to local Hounsfield number. Boundary conditions were then applied to the model to replicate the physiological loads. The effect of void-filling calcium triphosphate cement was analysed. Results. When the void was filled with calcium triphosphate cement, the pressure gradient of the bone surrounding the screws in the medial fracture fragment decreased 97% from up to 21.41 to 0.66 MPa. Peak pressure of the fracture planes decreased 95% from 6.10 to 0.30 MPa and occurred along the medial aspect. The mean stress in the screw locking mechanisms decreased 78% from 71.23 to 15.92 MPa. The angled proximal metaphyseal screw had the highest stress. Conclusion. Augmentation with calcium triphosphate cement improves initial stability and reduces stress on the implant-bone interface.

An analytical solution for the stress state at stent-coating interfaces.

In this paper an analytical solution for the stress state in a coated stent is presented, with a particular focus on the interface stresses between the coating and stent. As a first step a simplified stent architecture consisting of a bi-layered composite elastic arch is considered. The variations of normal and shear stress at the interface as functions of the boundary conditions at the base of the arch are explored. Depending on applied displacement and rotation, very distinct distributions of stress occur along the interface: dominant shear or dominant normal stress, compressive or tensile normal stress. A bi-layered composite elastic strut is then added to the composite elastic arch in order to create a realistic coated stent geometry. A displacement is applied to the bottom of the strut to simulate stent deployment. The addition of the strut is found to increase the normal stress and decrease the shear stress at all points on the interface. The influence of the various geometrical and material parameters on interface stress is explored using the analytical procedure developed in the paper, providing practical insight for stent-coating design.

Multi-axial damage and failure of medical grade carbon fibre reinforced PEEK laminates: Experimental testing and computational modelling

Orthopaedic devices using unidirectional carbon fibre reinforced poly-ether-ether-ketone (PEEK) laminates potentially offer several benefits over metallic implants including: anisotropic material properties; radiolucency and strength to weight ratio. However, despite FDA clearance of PEEK-OPTIMA™ Ultra-Reinforced, no investigation of the mechanical properties or failure mechanisms of a medical grade unidirectional laminate material has been published to date, thus hindering the development of first-generation laminated orthopaedic devices. This study presents the first investigation of the mechanical behaviour and failure mechanisms of PEEK-OPTIMA™ Ultra-Reinforced. The following multi-axial suite of experimental tests are presented: 0° and 90° tension and compression, in-plane shear, mode I and mode II fracture toughness, compression of ±45° laminates and flexure of 0°, 90° and ±45° laminates. Three damage mechanisms are uncovered: (1) inter-laminar delamination, (2) intra-laminar cracking and (3) anisotropic plasticity. A computational damage and failure model that incorporates all three damage mechanisms is developed. The model accurately predicts the complex multi-mode failure mechanisms observed experimentally. The ability of a model to predict diverse damage mechanisms under multiple loading directions conditions is critical for the safe design of fibre reinforced laminated orthopaedic devices subjected to complex physiological loading conditions.

Compressibility and Anisotropy of the Ventricular Myocardium: Experimental Analysis and Microstructural Modelling

While the anisotropic behavior of the complex composite myocardial tissue has been well characterized in recent years, the compressibility of the tissue has not been rigorously investigated to date. In the first part of this study, we present experimental evidence that passive-excised porcine myocardium exhibits volume change. Under tensile loading of a cylindrical specimen, a volume change of 4.1±1.95% is observed at a peak stretch of 1.3. Confined compression experiments also demonstrate significant volume change in the tissue (loading applied up to a volumetric strain of 10%). In order to simulate the multiaxial passive behavior of the myocardium, a nonlinear volumetric hyperelastic component is combined with the well-established Holzapfel-Ogden anisotropic hyperelastic component for myocardium fibers. This framework is shown to describe the experimentally observed behavior of porcine and human tissues under shear and biaxial loading conditions. In the second part of the study, a representative volumetric element (RVE) of myocardium tissue is constructed to parse the contribution of the tissue vasculature to observed volume change under confined compression loading. Simulations of the myocardium microstructure suggest that the vasculature cannot fully account for the experimentally measured volume change. Additionally, the RVE is subjected to six modes of shear loading to investigate the influence of microscale fiber alignment and dispersion on tissue-scale mechanical behavior.

Analysis of the Active Response of Cells to Cyclic Loading Using a Modified AFM System

Dynamic mechanical loading is essential for cell function and tissue maintenance. In an effort to characterize the response of cells to cyclic deformation several in vitro studies have relied on the testing of large populations of cells seeded on 2D substrates or in 3D scaffolds and gels. However, such studies do not allow for the measurement of forces actively generated at a single cell level. In the present study deformation controlled cyclic loading experiments are performed on single osteoblasts at the whole cell level using a modified AFM system[1,2]. In addition to untreated cells, experiments are also performed on passive cells in which the actin cytoskeleton has been disrupted. A computational analysis of experimentally measured single cell forces reveals that passive cell behaviour is characterized by a non-linear visco-hyperelastic formulation and active forces generated by the actin cytoskeleton are accurately predicted by the a Hill-type contractility framework with tension dependent remodeling[3,4].Copyright