Abstract
Cells of the musculoskeletal system are known to respond to mechanical loading and chondrocytes within the cartilage are not an exception. However, understanding how joint level loads relate to cell level deformations, e.g. in the cartilage, is not a straightforward task. In this study, a multi-scale analysis pipeline was implemented to post-process the results of a macro-scale finite element (FE) tibiofemoral joint model to provide joint mechanics based displacement boundary conditions to micro-scale cellular FE models of the cartilage, for the purpose of characterizing chondrocyte deformations in relation to tibiofemoral joint loading. It was possible to identify the load distribution within the knee among its tissue structures and ultimately within the cartilage among its extracellular matrix, pericellular environment and resident chondrocytes. Various cellular deformation metrics (aspect ratio change, volumetric strain, cellular effective strain and maximum shear strain) were calculated. To illustrate further utility of this multi-scale modeling pipeline, two micro-scale cartilage constructs were considered: an idealized single cell at the centroid of a 100×100×100 μm block commonly used in past research studies, and an anatomically based (11 cell model of the same volume) representation of the middle zone of tibiofemoral cartilage. In both cases, chondrocytes experienced amplified deformations compared to those at the macro-scale, predicted by simulating one body weight compressive loading on the tibiofemoral joint. In the 11 cell case, all cells experienced less deformation than the single cell case, and also exhibited a larger variance in deformation compared to other cells residing in the same block. The coupling method proved to be highly scalable due to micro-scale model independence that allowed for exploitation of distributed memory computing architecture. The method’s generalized nature also allows for substitution of any macro-scale and/or micro-scale model providing application for other multi-scale continuum mechanics problems.
Highlights
The phenomenon of cell behavior being directed by mechanical stimuli, referred to as mechanotransduction or mechanoregulation, as well as cell damage resulting from mechanical disruption, have been a topic of research in medicine and biology for several decades [1,2,3]
The cell(s) in both the single cell and 11 cell models experienced amplified deformation when compared to the macro-scale finite element deformation which drove the mechanics at the micro-scale model exterior
The data spread increased as the corresponding macro-scale deformation increased, with the effect magnified in the 11 cell case
Summary
The phenomenon of cell behavior being directed by mechanical stimuli, referred to as mechanotransduction or mechanoregulation, as well as cell damage resulting from mechanical disruption, have been a topic of research in medicine and biology for several decades [1,2,3]. While cellular activity at the micro-scale alters the mechanical environment, loading transferred from higher spatial scales plays a role [4] For this reason, the search for a better understanding of multi-scale spatial interactions has become an increasingly desirable objective, in order to establish the causal mechanical relationships between the loading of joints, tissues, and cells. The progression of OA exhibits changes in tissue structure [7,8,9], as well as changes in cellular (chondrocyte) distribution and behavior [10,11,12,13,14] While these changes occur at the tissue or cellular scales, a general consensus exists that the loading of the joints likely plays a role in their onset. Cartilage mechanics is a multi-scale paradigm and a means to investigate the interplay between scales is crucial to extending the understanding of the in vivo function of this biological material
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
