Multiscale Mechanics of Articular Cartilage: Potentials and Challenges of Coupling Musculoskeletal, Joint, and Microscale Computational Models

Abstract

Articular cartilage experiences significant mechanical loads during daily activities. Healthy cartilage provides the capacity for load bearing and regulates the mechanobiological processes for tissue development, maintenance, and repair. Experimental studies at multiple scales have provided a fundamental understanding of macroscopic mechanical function, evaluation of the micromechanical environment of chondrocytes, and the foundations for mechanobiological response. In addition, computational models of cartilage have offered a concise description of experimental data at many spatial levels under healthy and diseased conditions, and have served to generate hypotheses for the mechanical and biological function. Further, modeling and simulation provides a platform for predictive risk assessment, management of dysfunction, as well as a means to relate multiple spatial scales. Simulation-based investigation of cartilage comes with many challenges including both the computational burden and often insufficient availability of data for model development and validation. This review outlines recent modeling and simulation approaches to understand cartilage function from a mechanical systems perspective, and illustrates pathways to associate mechanics with biological function. Computational representations at single scales are provided from the body down to the microstructure, along with attempts to explore multiscale mechanisms of load sharing that dictate the mechanical environment of the cartilage and chondrocytes.

Altered swelling and ion fluxes in articular cartilage as a biomarker in osteoarthritis and joint immobilization: a computational analysis

“…It serves as a load-bearing material of the joints, providing excellent lubrication and great wear characteristics [4]. Besides, it bears compressive and shear stresses owing to cyclic and intermittent loads [5].…”

Modelling approaches for evaluating multiscale tendon mechanics

“…muscle, ligament, cartilage, meniscus, bone) to analyse functions of musculoskeletal joints [46,130,131]. For example, a three-dimensional model of the glenohumeral joint of the shoulder incorporated the long head of the biceps tendon as a transversely isotropic, hyperelastic material with a constant elastic modulus.…”

“…Although recent studies have demonstrated that ultrasonography and magnetic resonance imaging can be used to examine in vivo tissue abnormalities during the treatment of tendon injuries [42][43][44], more information, not just tissue stiffness and strain, needs to be extracted from experimental studies to improve understanding of mechanisms governing tendon responses in complex loading environments [45]. Modelling and simulation can function as complementary modules to mimic the physiological interactions of tendon with other structures, evaluate its mechanical properties under rsfs.royalsocietypublishing.org Interface Focus 6: 20150044 normal function, and predict disease-related perturbations or efficiency of injury treatments [46]. Importantly, most previous experimental studies of tendon structure-function relationships examined properties only at a single length scale (i.e.…”

Systems approaches in osteoarthritis: Identifying routes to novel diagnostic and therapeutic strategies

“…The use of animal models adds a layer of complexity to this problem and appropriate regard must be given to the spatial and temporal differences in these models. Figure developed from concepts described in refs 3, 21, 61, 63…”

“…OA cannot be considered a single disease with a linear narrative describing its pathogenesis, rather it is a heterogenous condition of multiple causation with a degenerate, non‐functional joint the common end‐point 2. Subject to repetitive cycles of loading over many years the joint represents the functional product of integrated multisystem, multiphysics, and multiscale units 3. The objective of this review is to consider afresh whether the osteoarthritis research community has tackled the need for novel OA therapeutics and diagnostics by applying recent developments in systems biology.…”