A microstructural model of osteochondral remodelling in an arthritis mouse model (in vivo)


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This is one of two research projects studying the onset and progress of arthritis. Melbourne is the home institution for this project. View the KU Leuven-based partner project.

Please be advised that applications are no longer being accepted for this project

Micro-computed tomography is an imaging modality for capturing data across length- and timescales. It is rapid, accurate and offers the necessary spatial resolution (5–50 m) to visualise and quantify structural and biochemical change resulting from biological remodelling. In the group of Dr Stok, it has been harnessed to image live animals at regular intervals to visualise remodelling triggered by arthritis. The next step is to combine this with sophisticated computational models to link structural remodelling to changes in mechanical properties at the interface between cartilage and bone (osteochondral interface).

The aim of this PhD project is to develop a microstructural finite element analysis of osteochondral remodelling in murine knees. MicroCT data is collected in a mouse model of arthritis using existing protocols. The longitudinal image data will be used as the input for micro-finite element models, in partnership with Prof van Lenthe (KU Leuven). The PhD candidate will (1) develop image analysis and registration methods to determine osteochondral remodelling, (2) develop a microstructural computational model to describe tissue mechanics, and (3) combine remodelling data with computational modelling to evaluate arthritis progression.

The computational model will help explain adaptive responses in cartilage and bone in healthy and disease conditions in the mouse. The model is expected to serve as a basis for developing similar models for predicting onset and progression of osteoarthritis in humans, which is highly needed for the prevention and treatment of the disease.

Project goals

To investigate the bone-cartilage interface of the musculoskeletal joint and uncover its role in the progression of osteoarthritis using novel mechanical, computational and bioimaging approaches with the specific aims to:

  1. Develop a computational framework to quantify stresses and strains in the transition zone between cartilage and bone.
  2. Establish a microstructural finite element analysis of osteochondral remodelling from in vivo longitudinal microCT data.

Together these projects will provide a framework to study the role of the bone-cartilage interface in the onset and progression of OA. It will find application in animal models of OA where it can be used to elucidate how load-induced changes in subchondral bone can modify the stress transfer from cartilage to bone, even at the level of single cartilage cells.

Supervision team

The University of Melbourne: Associate Professor Kathryn Stok

KU Leuven: Professor Harry van Lenthe

Who we are looking for

We are seeking a PhD candidate with the following skills:

  • Demonstrated experience in the field of biomedical engineering.
  • Demonstrated experience with scientific computation.
  • Demonstrated ability to work independently and as part of a team.
  • Demonstrated time and project management skills.
  • Demonstrated ability to write research reports or other publications to a publishable standard (even if not published to date).
  • Excellent written and oral communication skills.
  • Demonstrated organisational skills, time management and ability to work to priorities.
  • Demonstrated problem-solving abilities.

Further details

The PhD candidate will benefit from the combined expertise of the project supervisors, and the embedding into two research environments.

Associate Professor Kathryn Stok's expertise is in microCT imaging, image processing and analysis and she will therefore contribute to the project in the field of experimental methods including micro-computed tomography imaging, image processing, image analysis, and high-precision mechanical testing of biological materials. The project will benefit from high-resolution microCT and GPU computing systems, chemical synthesis laboratories and the newly established Melbourne Mechanobiology lab equipped with single-cell and tissue-level mechanical testing, microscopy, cell-culture and biochemistry facilities. Access to animal housing and in vivo microCT is provided by the neighbouring School of Biosciences. Professor Harry van Lenthe will contribute in the field of computational methods with an emphasis on high-performance computing using the finite element method. In addition, he will provide support in the structural and mechanical characterization of bone including micro-computed tomography imaging, image processing and analysis, and high-precision mechanical testing.

This PhD project will be based at the University of Melbourne with a minimum 12-month stay at KU Leuven.

The candidate will be enrolled in the PhD program at the School of Biomedical and Chemical Engineering at the University of Melbourne and in the PhD program at the Department of Mechanical Engineering at KU Leuven.

Please be advised that applications are no longer being accepted for this project

First published on 1 February 2022.

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