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One fully funded PhD studentship - Ecole des Mines de Saint-Etienne, France.
Scope
Cardiovascular diseases are a major health problem in European and American countries. Vascular ageing is characterized by the presence of atheroma plaques, deposited on the inner wall of arteries, which progressively reduce the arterial lumen. Besides the high risk of stenosis, the thickening and calcification of the arterial wall lead to unfavorable tissue stiffening and embrittlement: the mechanical competences of the involved tissue are altered, increasing its risk towards fracture and rupture. In worst case, this triggers plaque rupture, with the detached material forming a thrombus slowing or stopping blood flow, which may have lethal consequences.
The evolution of these pathologies is highly influenced by the biomechanical environment, as well as by the mechanical properties of the tissue. Indeed, a strong coupling exists between the evolution of the arterial microstructure and the macroscopic response to mechanical loadings: the organization of the elementary constituents (collagen, elastin, and smooth muscle cells) determines the macroscopic mechanical response, while a change in the mechanical solicitation leads to tissue remodeling and therefore to a change in the mechanical properties of the tissue.
The microstructure reveals to be the central ingredient in this strong coupling. Our group recently developed a multiscale micromechanical model for the mechanical behavior of arterial wall that relate the macroscopic mechanical behavior to the microscopic deformation and rearrangement mechanisms inside the microstructure. This model covers one aspect of this strong coupling, namely the link between mechanics and microstructure. The aim of the present PhD project is to work on the other aspect of the coupling, namely how mechanobiology affects the microstructure
Working plan
In order to understand how mechanobiology affects the microstructure and consequently the mechanical behaviour of arteries, the PhD project will first focus on the extension of the arterial wall multiscale micromechanical model, and then on the development of a mechanobiological model based on a systems biology approach to account for the arterial wall remodeling. The latter model will predict, through the cellular activity, the evolution of the microstructure. Coupling the mechanical model with the mechanobiological one should allow to deal with the previously mentioned strong coupling.
More precisely, the proposed plan of the PhD is as follows:
Collaborations
This work will be done in close collaboration between the Center for Biomedical and Healthcare Engineering (SAINBIOSE, INSERM U1059) at the Ecole des Mines de Saint Etienne and the Institute for Mechanics of Materials and Structures at the Vienna University of Technology. The PhD work will also involve close collaboration with the vascular surgery service of the Saint-Etienne University Hospital (Prof. J-P. Favre, J-N Albertini) as well as with other current studies on aneurysm failure of human aorta carried out at INSERM U1059, in order to collect knowledge on the physiopathology of aortic aneurysm and on vascular biomechanics.
Keywords
Biomechanics ; Mechanobiology; arterial wall ; multiscale modeling
Student profile
Mechanical engineering or biomedical engineering.
Strong interest in mathematical modeling will be appreciated.
Supervision
Ecole des Mines de Saint Etienne :
Claire Morin, SAINBIOSE & CIS, Tel : +33 4 77 49 97 39 (claire.morin@emse.fr)
Stéphane Avril, SAINBIOSE & CIS, Tel : +33 4 77 42 01 88 (avril@emse.fr)
Scope
Cardiovascular diseases are a major health problem in European and American countries. Vascular ageing is characterized by the presence of atheroma plaques, deposited on the inner wall of arteries, which progressively reduce the arterial lumen. Besides the high risk of stenosis, the thickening and calcification of the arterial wall lead to unfavorable tissue stiffening and embrittlement: the mechanical competences of the involved tissue are altered, increasing its risk towards fracture and rupture. In worst case, this triggers plaque rupture, with the detached material forming a thrombus slowing or stopping blood flow, which may have lethal consequences.
The evolution of these pathologies is highly influenced by the biomechanical environment, as well as by the mechanical properties of the tissue. Indeed, a strong coupling exists between the evolution of the arterial microstructure and the macroscopic response to mechanical loadings: the organization of the elementary constituents (collagen, elastin, and smooth muscle cells) determines the macroscopic mechanical response, while a change in the mechanical solicitation leads to tissue remodeling and therefore to a change in the mechanical properties of the tissue.
The microstructure reveals to be the central ingredient in this strong coupling. Our group recently developed a multiscale micromechanical model for the mechanical behavior of arterial wall that relate the macroscopic mechanical behavior to the microscopic deformation and rearrangement mechanisms inside the microstructure. This model covers one aspect of this strong coupling, namely the link between mechanics and microstructure. The aim of the present PhD project is to work on the other aspect of the coupling, namely how mechanobiology affects the microstructure
Working plan
In order to understand how mechanobiology affects the microstructure and consequently the mechanical behaviour of arteries, the PhD project will first focus on the extension of the arterial wall multiscale micromechanical model, and then on the development of a mechanobiological model based on a systems biology approach to account for the arterial wall remodeling. The latter model will predict, through the cellular activity, the evolution of the microstructure. Coupling the mechanical model with the mechanobiological one should allow to deal with the previously mentioned strong coupling.
More precisely, the proposed plan of the PhD is as follows:
- The first year will be devoted to further developing and validating the mechanical model of the arterial wall tissue, based on experiments performed on different porcine, rabbit and human arteries (control and aneurysms).
- During the second year, a first sketch of a remodeling model will be proposed, to account first for the arterial wall calcifications. The model development will be performed in close collaborations with the Viennese institute led by Prof. Christian Hellmich (Vienna University of Technology), working on bone tissues, since it is widely accepted that the arterial wall calcifications result from the activity of bone-like cells within the arterial wall.
- Finally, the third year will be devoted to coupling the multiscale mechanical model to the mechanobiological model, and to validating the coupled model from experiments performed at the Centre for Biomedical and Healthcare Engineering.
Collaborations
This work will be done in close collaboration between the Center for Biomedical and Healthcare Engineering (SAINBIOSE, INSERM U1059) at the Ecole des Mines de Saint Etienne and the Institute for Mechanics of Materials and Structures at the Vienna University of Technology. The PhD work will also involve close collaboration with the vascular surgery service of the Saint-Etienne University Hospital (Prof. J-P. Favre, J-N Albertini) as well as with other current studies on aneurysm failure of human aorta carried out at INSERM U1059, in order to collect knowledge on the physiopathology of aortic aneurysm and on vascular biomechanics.
Keywords
Biomechanics ; Mechanobiology; arterial wall ; multiscale modeling
Student profile
Mechanical engineering or biomedical engineering.
Strong interest in mathematical modeling will be appreciated.
Supervision
Ecole des Mines de Saint Etienne :
Claire Morin, SAINBIOSE & CIS, Tel : +33 4 77 49 97 39 (claire.morin@emse.fr)
Stéphane Avril, SAINBIOSE & CIS, Tel : +33 4 77 42 01 88 (avril@emse.fr)
