Speaker: Prof. Stéphane Avril

Abstract

Growth and remodeling (GR) of biological tissues has been increasingly approached with the constrained mixture theory (CMT) to predict a variety of arterial mechanobiological behaviors. Most of previously published work has been limited to simplified cases as isotropic growth, axisymmetric motions, mono-layer wall and/or membrane approximations. Although such models have increased our insights in vascular adaptation, a 3D anisotropic bilayer model has the potential of considering more complex cases of arterial G&R such as aortic aneurysm.

Therefore, we have developed a computational model of the arterial wall taking into account major biological micro-components such as elastin, collagen fibers and smooth muscle cells (SMC) and their mechanical interactions. The contractility of SMC and turnover of collagen fibers are assumed stress dependent. Simulations are performed on geometries reconstructed from the CT scan of patients harboring an ascending thoracic aortic aneurysm (ATAA), subjected to boundary conditions in homeostatic conditions. Two different mechanisms are considered for the initiation of aneurysm enlargement, namely loss of SMC contractility and proteolytic injury. The models are able to predict realistic aneurysm progression as confirmed by a follow-up MRI performed on the same patients. Our findings indicate the determinant role of SMC contractility during ATAA growth. Recent work in our group focus on applying continuum mechanics at the cellular level to better decipher this major role played by SMCs in maintaining the integrity of the human aorta.

Biography

Stéphane Avril is a distinguished Full Professor at Institut Mines Telecom (IMT) affiliated at Mines Saint-Etienne and Université de Lyon in France. He runs a group of 20+ in soft tissue biomechanics, with a special focus on constitutive modeling and identification using imaging techniques. After being the director of the CIS center for biomedical and healthcare engineering (65+ people), he is now deputy director of SAINBIOSE (INSERM endorsed laboratory with 100+ researchers).

Stéphane received his PhD in mechanical and civil engineering in 2002 at Mines Saint-Etienne (France). After positions at Arts et Métiers ParisTech (France) and Loughborough University (UK) where he developed the Virtual Fields Methods, Stéphane returned to his alma mater in 2008 and extended his broad experience of inverse problems to soft tissue biomechanics, especially regarding aortic aneurysms in close collaboration with vascular surgeons. Stéphane was a visiting Professor at the University of Michigan Ann Arbor (USA) in 2008 and a visiting professor at Yale University between 2014 and 2019. He has been a guest professor at the Technische Universität Wien in Austria since 2020.

Stéphane has received several awards and distinctions including ICCB best communication award (2017), Editor’s Choice Paper Finalist – ASME Journal of Biomechanical Engineering (2016), ESB best poster award (2015), BSSM 50th Anniversary Plenary Speaker (2014). He has led two national ANR grants in soft tissue biomechanics, supervised 30+ PhD students and 15+ postdocs. In 2015, Stéphane was awarded an ERC (European Research Council) consolidator grant of 2m€ for the Biolochanics project on: Localization in biomechanics and mechanobiology of aneurysms: Towards personalized medicine. Stéphane is also co-PI in several other European project, including a Marie Curie ITN.

Most of Stéphane’s research is aimed at improving the treatment of cardiovascular diseases by assisting physicians and surgeons with biomechanical numerical simulations. In 2017, Stéphane co-founded Predisurge, a spin-off company of IMT at Mines Saint-Etienne, now employing 20 people. PrediSurge offers innovative software solutions for patient-specific numerical simulation of surgical procedures.

Notes

• The continuum mechanics model for the aorta wall consists of a "passive" material part and an "active" biological part. The passive behaviour is described by a composite hyperelastic model with a strain-energy function based on the CMT. The biological effects include the growth and remodelling of collagen fibers. Growth is dictated by the deviation of the fiber stress from its homeostatic value. Remodelling corresponds to the inelastic deformation induced by the collagen fibers as they tend to follow the growth of an aneurysm to maintain a constant tension level. The system's response to a localized destruction of elastin is studied.


• The model is sensitive to the boundary and initial conditions, which are patient specific. The mechanical approach is therefore combined to a statistical model to learn the boundary conditions, initial conditions, and material properties from image analysis.


• An AI model is used to identify rupture initiation with a 95% success rate. A criterion solely based on stress distribution is unreliable as rupture is also strongly correlated to the growth rate of collagen fibers.


• Traction force microscopy is used to determine the forces applied by the cells. The cells are grown on a gel bed embedded with fluorescent microbeads. Using DIC, the strain field can be computed and the associated stress field is deduced from the constitutive model of the gel.

Suggested readings

• S.J. Mousavi, S. Farzaneh, S. Avril.
  Patient-specific predictions of aneurysm growth and remodeling in the ascending thoracic aorta using the homogenized constrained mixture model.
  Biomech Model Mechanobiol 18, 1895–1913, 2019.


• C.J. Cyron, R.C. Aydin, J.D. Humphrey.
  A homogenized constrained mixture (and mechanical analog) model for growth and remodeling of soft tissue.
  Biomech Model Mechanobiol 15, 1389-1403, 2016.


• C.L.M. Gouget, Y. Hwang, A.I. Barakat.
  Model of cellular mechanotransduction via actin stress fibers.
  Biomech Model Mechanobiol 15, 331–344, 2016.


• C. Bellini, J. Ferruzzi, S. Roccabianca et al.
  A Microstructurally Motivated Model of Arterial Wall Mechanics with Mechanobiological Implications.
  Ann Biomed Eng 42, 488–502, 2014.

LMS seminars on related topics

• 07/01//2021, Prof. Gerard Ateshian, Thermodynamics of Constrained Reactive Mixtures