On the monolithic and staggered solution of cell contractility and focal adhesion growth.

The mechanical response of cells to stimuli tightly couples biochemical and biomechanical processes, which describe fundamental properties such as cell growth and reorientation. Cells interact continuously with their external surroundings, the extracellular matrix (ECM), by establishing a bond between cell and ECM through the formation of focal adhesions. Focal adhesions are made up of integrins, which are mechanosensitive proteins and responsible for the communication between the cell and the ECM. The governing biochemomechanical processes can be modeled by means of a continuum approach considering mechanical and thermodynamic equilibrium to describe cell contractility and focal adhesion growth. The immanent multiphysical character of cell mechanics involves important aspects such as the coupling of fields of different scales and corresponding interface conditions that are sensitive to the solution of the governing numerical problem. These aspects become even more relevant when considering a feedback loop among the multiphysical solutions fields. In this contribution, we consider solution properties and sensitivity aspects of a nonlinear mechanical continuum model for the prognosis of stress fiber growth and reorientation incorporating a mechanosensitive feedback loop. We provide the governing equations of a Hill model-based stress fiber growth, which is coupled to a thermodynamical approach modeling the focal adhesions. Furthermore, a variational formulation including the algebraic equations is derived for staggered and monolithic solution approaches and the reaction-diffusion equation that models the feedback mechanism. We test both schemes with regard to reliability, accuracy, and numerical efficiency for different model parameters and loading scenarios. We present algorithmic aspects of the considered solution schemes and reveal their robustness with regard to model refinement in space and time and finally provide an assessment of their overall solution performance for multiphysics problems in the context of cell mechanics.

Multi-level hp-finite cell method for embedded interface problems with application in biomechanics.

This work presents a numerical discretization technique for solving 3-dimensional material interface problems involving complex geometry without conforming mesh generation. The finite cell method (FCM), which is a high-order fictitious domain approach, is used for the numerical approximation of the solution without a boundary-conforming mesh. Weak discontinuities at material interfaces are resolved by using separate FCM meshes for each material sub-domain and weakly enforcing the interface conditions between the different meshes. Additionally, a recently developed hierarchical hp-refinement scheme is used to locally refine the FCM meshes to resolve singularities and local solution features at the interfaces. Thereby, higher convergence rates are achievable for nonsmooth problems. A series of numerical experiments with 2- and 3-dimensional benchmark problems is presented, showing that the proposed hp-refinement scheme in conjunction with the weak enforcement of the interface conditions leads to a significant improvement of the convergence rates, even in the presence of singularities. Finally, the proposed technique is applied to simulate a vertebra-implant model. The application showcases the method's potential as an accurate simulation tool for biomechanical problems involving complex geometry, and it demonstrates its flexibility in dealing with different types of geometric description.

Phase-field boundary conditions for the voxel finite cell method: Surface-free stress analysis of CT-based bone structures.

The voxel finite cell method uses unfitted finite element meshes and voxel quadrature rules to seamlessly transfer computed tomography data into patient-specific bone discretizations. The method, however, still requires the explicit parametrization of boundary surfaces to impose traction and displacement boundary conditions, which constitutes a potential roadblock to automation. We explore a phase-field-based formulation for imposing traction and displacement constraints in a diffuse sense. Its essential component is a diffuse geometry model generated from metastable phase-field solutions of the Allen-Cahn problem that assumes the imaging data as initial condition. Phase-field approximations of the boundary and its gradient are then used to transfer all boundary terms in the variational formulation into volumetric terms. We show that in the context of the voxel finite cell method, diffuse boundary conditions achieve the same accuracy as boundary conditions defined over explicit sharp surfaces, if the inherent length scales, ie, the interface width of the phase field, the voxel spacing, and the mesh size, are properly related. We demonstrate the flexibility of the new method by analyzing stresses in a human femur and a vertebral body.

Uncertainty quantification for personalized analyses of human proximal femurs.

Computational models for the personalized analysis of human femurs contain uncertainties in bone material properties and loads, which affect the simulation results. To quantify the influence we developed a probabilistic framework based on polynomial chaos (PC) that propagates stochastic input variables through any computational model. We considered a stochastic E-ρ relationship and a stochastic hip contact force, representing realistic variability of experimental data. Their influence on the prediction of principal strains (ϵ1 and ϵ3) was quantified for one human proximal femur, including sensitivity and reliability analysis. Large variabilities in the principal strain predictions were found in the cortical shell of the femoral neck, with coefficients of variation of ≈40%. Between 60 and 80% of the variance in ϵ1 and ϵ3 are attributable to the uncertainty in the E-ρ relationship, while ≈10% are caused by the load magnitude and 5-30% by the load direction. Principal strain directions were unaffected by material and loading uncertainties. The antero-superior and medial inferior sides of the neck exhibited the largest probabilities for tensile and compression failure, however all were very small (pf<0.001). In summary, uncertainty quantification with PC has been demonstrated to efficiently and accurately describe the influence of very different stochastic inputs, which increases the credibility and explanatory power of personalized analyses of human proximal femurs.

The finite cell method for bone simulations: verification and validation.

Standard methods for predicting bone's mechanical response from quantitative computer tomography (qCT) scans are mainly based on classical h-version finite element methods (FEMs). Due to the low-order polynomial approximation, the need for segmentation and the simplified approach to assign a constant material property to each element in h-FE models, these often compromise the accuracy and efficiency of h-FE solutions. Herein, a non-standard method, the finite cell method (FCM), is proposed for predicting the mechanical response of the human femur. The FCM is free of the above limitations associated with h-FEMs and is orders of magnitude more efficient, allowing its use in the setting of computational steering. This non-standard method applies a fictitious domain approach to simplify the modeling of a complex bone geometry obtained directly from a qCT scan and takes into consideration easily the heterogeneous material distribution of the various bone regions of the femur. The fundamental principles and properties of the FCM are briefly described in relation to bone analysis, providing a theoretical basis for the comparison with the p-FEM as a reference analysis and simulation method of high quality. Both p-FEM and FCM results are validated by comparison with an in vitro experiment on a fresh-frozen femur.