Herzog, WalterFederico, SalvatoreSibole, Scott2022-08-242022-08-242022-08Sibole, S. (2022). Towards understanding multiscale articular cartilage mechanics (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.http://hdl.handle.net/1880/115130The mechanical environment of the chondrocytes, the sole cell type in articular cartilage, is of high importance to developing and maintaining a healthy tissue state. Mechanical cues play a major role in the regulation of many cellular functions. The dominant mechanics experienced by chondrocytes are translated from physics occurring at the scale of the body (1 m) to the cellular scale (1×10−5 m). This large breadth of scale leads to many challenges when investigating chondrocyte mechanics both mathematically and experimentally. A popular mathematical approach is to solve boundary value problems defined by the governing equations from classical mechanics at different spatial scales such as the body, joint, tissue, and cellular with some defined coupling between them. Such multiscale modelling offers great investigative scope, but also requires many technical considerations that necessitate validation. Experimentation can offer a means for validation and additional investigation. A popular experimental approach employs laser scanning microscopy coupled with mechanical testing systems capable of acquiring 3-D images of tissue subjected to controlled mechanical conditions. By comparing tissue volumes in different mechanical states, micro-scale deformation can be calculated. This work focused on the extension of the current analysis toolkit of such multiscale experimental data. Software was developed for improved segmentation of cellular scale geometries. A novel experimental method and analysis software were developed that utilized deformable image registration to quantify tissue deformation. A specimen staining and imaging protocol for morphometrics of the pericellular matrix was developed along with data analysis software. These morphometrics revealed a distinct directed pericellular matrix asymmetry, which was investigated through multiscale finite element modelling. Simulations indicated that such directed asymmetry may provide mechanical protections to the cellular membrane during fast-loading conditions. Finally, the image acquisition rate of laser scanning microscopy has historically restricted it to measuring steady-state mechanics. To circumvent this limitation, the rapid acquisition rate of resonance scanning was employed to measure transient cellular-scale mechanics. A software package to quantify tissue and cellular deformation from resonance-scanned images was developed. Resonance scanning and the subsequent analysis exhibited robust and accurate performance indicating its usefulness as a tool to study such dynamics.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.Engineering--Biomedicaldoctoral thesis