A Review of the Combination of Experimental Measurements and Fibril-Reinforced Modeling for Investigation of Articular Cartilage and Chondrocyte Response to Loading

Abstract

The function of articular cartilage depends on its structure and composition, sensitively impaired in disease (e.g. osteoarthritis, OA). Responses of chondrocytes to tissue loading are modulated by the structure. Altered cell responses as an effect of OA may regulate cartilage mechanotransduction and cell biosynthesis. To be able to evaluate cell responses and factors affecting the onset and progression of OA, local tissue and cell stresses and strains in cartilage need to be characterized. This is extremely challenging with the presently available experimental techniques and therefore computational modeling is required. Modern models of articular cartilage are inhomogeneous and anisotropic, and they include many aspects of the real tissue structure and composition. In this paper, we provide an overview of the computational applications that have been developed for modeling the mechanics of articular cartilage at the tissue and cellular level. We concentrate on the use of fibril-reinforced models of cartilage. Furthermore, we introduce practical considerations for modeling applications, including also experimental tests that can be combined with the modeling approach. At the end, we discuss the prospects for patient-specific models when aiming to use finite element modeling analysis and evaluation of articular cartilage function, cellular responses, failure points, OA progression, and rehabilitation.

Tension tests on mammalian collagen fibrils

“…These studies have applications as varied as understanding mechanotransduction and fracture in tissues, such as bone [1], tendon [2], cartilage [3], skin [4] and cornea [5]. The structures of such collagen-based extracellular matrices have been studied extensively dating back to the earliest works of Leeuwenhoek [6].…”

The Influence of Cell-Matrix Attachment and Matrix Development on the Micromechanical Environment of the Chondrocyte in Tissue-Engineered Cartilage

“…28 Besides these agreements, it is also worth mentioning that the constitutive material model for native ECM has previously been validated and used for studies at both the macroscopic tissue 21,22,30 and the microscopic cell level. 24,[31][32][33][34][35][36] The different macroscopic and microscopic depthdependent strain fields between native cartilage and TE constructs may have implications for the mechano-response of the chondrocytes to mechanical stimulation. Cells may have adapted over time to particular in vivo environments, which may or may not resemble those that are exposed to in TE constructs, depending on the location where they end up after seeding.…”

“…One of the limitations in this and other 26,36 modeling studies is that the chondrocyte is idealized as a homogeneous continuum. Subcellular components, such as the nucleus and cytoskeletal fibers, modulate the intracellular strain field.…”

Clinical curative effect of repair surgery for treatment of articular cartilage injury

“…Articular cartilage injury, one of the most common clinical joint diseases, is mainly caused by internal or external factors, and the incidence rate of knee joint injury is high [1]. The articular cartilage of knee joint lacks blood vessels, nerves, and lymph tissues; thus, the joint exhibits poor self-repair ability.…”