Clinical Mechanobiology

Validated in silico models and computational tools will reduce both the amount of experimental studies and number of study participants required to develop novel treatments for bone diseases. This is due to the possibility to test hundreds of configurations in silico in a far shorter time period and at a drastically lower cost than when running experiments. With the advent of in vivo high-resolution imaging modalities, changes in microstructural and mechanical properties of individual patients can be assessed over time. In combination with such longitudinal validation data, development of clinically relevant mechanobiological models and tools requires an understanding of bone as a model system as well as state-of-the-art numerical and computational methods.

Our Goal

Within the clinical mechanobiology team, our goal is to integrate non-invasive imaging methods with experimental and computational mechanics in order to develop clinically applicable tools to monitor bone integrity, fracture risk, and fracture healing in patients. Through this, we aim to better understand and model how the mechanobiological pathways in bone modulate its structure and physiology from cell to organ scale, and how diseases and treatments perturb this system.  

Our Expertise

We develop in silico models of bone healing and remodeling which provide a window into microscale processes, which would be unobtainable with existing experimental methods. At the same time, we develop novel analyses of in vivo patient data which can provide insight into the fundamental mechanobiology and serve to parametrize and validate our model. Team members have a variety of backgrounds in engineering and science, and we routinely interface with collaborators in both pre-clinical and clinical settings, allowing a valuable exchange of expertise, data, and insights.

Projects

Bone Mechanoregulation in Type II Diabetes - FIDELIO

Bone fragility is dependent not only on bone mass, but on microstructure and the intrinsic material properties of the tissue as well. Although fracture risk is increased in diabetic patients, clinical assessment of bone fragility in T2D is particularly challenging because patients have an elevated fracture risk despite having normal or even high bone mineral density (BMD). Current clinical diagnostic techniques such as dual-energy x-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT), which consider BMD but not material strength, are therefore not able to accurately assess bone fragility in T2D.  

Link to FIDELIO Project
FIDELIO

Within the FIDELIO-project.eu, we are working to propel image processing and computational methods for mechanobiological bone remodelling studies from bench (supercomputer) to bedside (clinical computing). These approaches will then be used to investigate the effects of diabetes on local mechanoregulation of bone remodelling in T1D and T2D as well as appropriate controls, identifying their relationship to bone fragility and in vivo biomarkers, which are directly linked to this impairment in mechanoregulation.

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Micro-​multiphysics Modelling of Osteoporosis and its Treatments

The 9 million osteoporotic fragility fractures that occur every year currently lead to over 400,000 deaths and health care costs in excess of US$80 billion. In silico models could provide a fast and inexpensive tool for testing hypotheses on bone remodeling and for informing clinical trial design; in pre-clinical applications, these models have been shown to make patient-specific predictions of bone degeneration and response to therapeutics.

link to Multiphysics project page
Micro-multiphysics modelling of osteoporosis and its treatments

This project aims to evaluate the robustness of a novel micro-multiphysics (micro-MP) model that integrates mechanics, cell behavior and reaction-diffusion of signaling molecules and validate the model using longitudinal high-resolution peripheral quantitative computed tomography (HR-pQCT) images. Upon validation, the model could be used to inform the design of clinical trials and as a method to gain further insights into bone biology and treatments’ method of action.

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In Silico Modelling of Bone Organoids  

Understanding the underlying molecular mechanisms and structural changes that occur during bone remodelling are crucial for the development of treatments for bone diseases. Animal models are used to overcome the limitations of the sparse number of patients, as diseased animals can be bred and used to test new treatments.

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In silico modelling of bone organoids
In silico modelling of bone organoids  
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