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PhD Studentship: A novel multi-scale computational model to evaluate the effect of musculoskeletal

Employer
Global Academy Jobs
Location
United Kingdom
Closing date
Jan 24, 2018

Job Details

Details

Bone remodelling (BR) is affected by musculoskeletal pathologies such as osteoporosis and osteoarthritis. Therefore, in order to develop new interventions for such diseases a comprehensive understanding of BR in healthy, pathological and treated condition is needed.

Currently, the efficacy of novel musculoskeletal interventions needs to be tested on animals before its application to clinical studies. Mice models are used intensively due to their low cost and the possibility of performing advanced measurements such as in vivo micro computed tomography (microCT). Computational models that predict the effect of diseases and related interventions on the BR and on the bone densitometric, morphometric and mechanical properties, can be a potential tool to optimise treatments and to reduce and partially replace the usage of mice in musculoskeletal research. Nevertheless, BR is a complex physical phenomenon hard to be modelled due to its multi-scale nature: the bone cells remodel the bone tissue due to local biochemical stimuli and to mechanical stimuli that are heterogeneously distributed on the tissue under external loads applied to the whole bone. Moreover, before any applications, the outcomes of the models need to be calibrated and independently validated by comparison with accurate experimental analyses.

In this project for the first time we will develop, calibrate and validate a multi-scale computational model of BR and test it for different musculoskeletal interventions. The model will be based on the combination of physiology-based finite element (FE) models, which evaluate the mechanical stimuli in the whole bone given a certain loading condition, and ordinary differential equations (ODE), which model the effect of combined mechanical and biochemical stimuli on the cell activity. The combination of the two models will allow predicting the effect of interventions that affect the mechanics (e.g. physical exercise) and/or the biochemistry of the bone (e.g. injection of anabolic treatments) on the BR over time. With the combination of the two models applied to an initial high resolution scan of the mouse tibia we will be able to estimate the bone changes over time in mice treated or not with mechanical or biochemical interventions. The outcomes of the models will be validated against measurement of changes in bone properties using longitudinal in vivo microCT analyses of the mouse tibia.

The successful model can be used to predict the effect of novel interventions given a small dataset from in vivo animal studies for proper calibration and could be used to predict the bone changes in case, for example, of different doses, administration times or combination of treatments.

 

Eligibility Requirements

The successful candidate should have or be expected to obtain a 1st class or a good 2.1 degree in mechanical engineering, bioengineering, computer science, physics, applied mathematics or a related discipline.

 

Funding Notes

Doctoral Academy Scholarships:

The Faculty Scholarships for Medicine, Dentistry & Health cover fees and stipend at Home/EU level. Overseas students may apply but will need to fund the fee differential between Home and Overseas rate from another source.

 

Chinese Scholarship Award:

For eligibility requirements please see the following link https://www.sheffield.ac.uk/postgraduate/research/scholarships/csc

The Chinese Scholarship Award cover fees and stipend including any additional overseas level fees.

 

References

  1. Lu Y, Boudiffa M, Dall'Ara E, Liu Y, Bellantuono I, Viceconti M. Longitudinal effects of Parathyroid Hormone treatment on morphological, densitometric and mechanical properties of mouse tibia. J Mech Behav Biomed Mater. 2017 Nov;75:244-251
  2. Chen Y, Dall Ara E, Sales E, Manda K, Wallace R, Pankaj P, Viceconti M. Micro-CT based finite element models of cancellous bone predict accurately displacement once the boundary condition is well replicated: A validation study. J Mech Behav Biomed Mater. 2017 Jan;65:644-651
  3. Dall'Ara E, Boudiffa M, Taylor C, Schug D, Fiegle E, Kennerley AJ, Damianou C, Tozer GM, Kiessling F, Müller R. Longitudinal imaging of the ageing mouse. Mech Ageing Dev. 2016 Dec;160:93-116
  4. Oliviero S, Lu Y, Viceconti M, Dall’Ara E. Effect of integration time on the Morphometric, Densitometric and Mechanical Properties of the Mouse Tibia. Under review in JBiomech
  5. Razi H, Birkhold AI, Weinkamer R, Duda GN, Willie BM, Checa S. Aging Leads to a Dysregulation in Mechanically Driven Bone Formation and Resorption. J Bone Miner Res. 2015 Oct;30(10):1864-73
  6. Levchuk A, Zwahlen A, Weigt C, Lambers FM, Badilatti SD, Schulte FA, Kuhn G, Müller R. The Clinical Biomechanics Award 2012 - presented by the European Society of Biomechanics: large scale simulations of trabecular bone adaptation to loading and treatment. Clin Biomech (Bristol, Avon). 2014 Apr;29(4):355-62
  7. Lerebours C, Buenzli PR, Scheiner S, Pivonka P. A multiscale mechanobiological model of bone remodelling predicts site-specific bone loss in the femur during osteoporosis and mechanical disuse. Biomech Model Mechanobiol. 2016 Feb;15(1):43-67
  8. Lu Y, Boudiffa M, Dall'Ara E, Bellantuono I, Viceconti M. Development of a protocol to quantify local bone adaptation over space and time: Quantification of reproducibility. J Biomech. 2016 Jul 5;49(10):2095-2099
  9. Charles JP, Cappellari O, Spence AJ, Wells DJ, Hutchinson JR. Muscle moment arms and sensitivity analysis of a mouse hindlimb musculoskeletal model. J Anat. 2016 Oct;229(4):514-35."

 

Company

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