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A computational tool to elucidate the mechanobiological regulation of limb development

Objective

Understanding the roles of motion and mechanotransduction in joint formation holds promise for the study and treatment of joint deformities in humans. Joint development has been widely studied in axolotls (Ambystoma mexicanum), as these animals regrow whole limbs throughout their life. Axolotl limbs are morphologically similar to human limbs and utilize the same biological rubrics as ontogenic growth. To draw from the therapeutic potential of these similarities, we propose to build a multi-scale multi-physics computational model for the prediction of vertebrate limb development. Our model will be based on in vivo data obtained using novel imaging techniques via NSF-funded experiments on axolotl limb growth, and will be utilised to determine the physical mechanisms of normal and pathological joint morphogenesis. To this end, in AIM 1 we will build a finite element model of growth at the tissue level to study how specific changes in limb motion regulate joint morphology. Next, in AIM 2 we will build a model of growth at the molecular level to determine how biochemical and biomechanical signalling pathways interact during normal and pathological joint development. Finally, in AIM 3 we will integrate both experimental and computational data from the different length scales into a single multi-scale mechano-biochemical model of vertebrate limb growth. A computational model that links the biomechanics and biochemistry of normal and pathological limb development at the subcellular, cellular and tissue scales is a powerful predictive tool. We envisage this tool will be utilised to optimise treatment therapies for joint deformities and better inform the preventive screening of congenital defects in humans.
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Coordinator

UNIVERSITAT POLITECNICA DE CATALUNYA

Address

Calle Jordi Girona 31
08034 Barcelona

Spain

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 245 732,16

Partners (1)

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NORTHEASTERN UNIVERSITY

United States

Project information

Grant agreement ID: 841047

Status

Ongoing project

  • Start date

    6 May 2019

  • End date

    5 May 2022

Funded under:

H2020-EU.1.3.2.

  • Overall budget:

    € 245 732,16

  • EU contribution

    € 245 732,16

Coordinated by:

UNIVERSITAT POLITECNICA DE CATALUNYA

Spain