Multiscale Approach to the Study of the Mechanics of Living Beings .

1. MultiscaleApproach to the Study of the Mechanics of Living Beings. benyebka.bou-said@insa-lyon.fr Numerical and experimentalmodelsassuming the coupling of mechanics / physics/chemistry/biology Multiscaleapproach to soft tissue (skin, artery, cartilage. etc.) To understand the link between causes and consequences To optimize: Diagnosis - Prevention - Treatment of Pathologies Security - Public health

2. Multiscaleapproach - mechanics of living beings Skin Joints Pathologies of biological contacts Soft tissue behavior Vascular system Vascular pathologies - detectionand treatment.

3. Plan Context / Objectives Strategy / applications Methodology Conclusions Future Reserach

4. Implants Lifetime not guaranteed ‘drastic’ treatment Objectives • Evolution of mechanicalpropertiesfromhealthypathological • Predictpathologicalevolutionearlydiagnosis • Realisticprediction of implant lifetime • Develop new treatments – less ‘drastic’ v Ex-vivo simulations realistic ? (mechanism, lubricant, interfaces) Context / Objectives Pathologies Asymptomatic Difficult for an early detection N ARTHRITIS wear ATHEROMA 1 cm

5. Context/ Objectives Objectives To know the response of living tissues to shockloading to improve the safetysystems in cars and trucks Perfect sports bra should be like a second skin, supporting firmly the breasts while letting them breathe for better comfort Patm Fluid flowoutside the contact (V2) Fabric P0 (homogenized pressure) Fluid flowinside the contact(V1) skin Human skin-synthetic fabric Security Soft tissues submited to shockloading FE modelling of soft tissue predictrisks of injury in car crash

6. Strategy To understand the link between causes and consequences To optimize: Diagnosis - Prevention - Treatment of Pathologies Mechanical cause : mechanical transmission Shockstissue damages Real stress Physico-chemical cause : Lubricant / Interfaces Molecular assembling destruction Acceptable stress Biological cause : Tissue Cell genetic mutations  change mechanical properties of cells and extracellular matrix 3 causes  1 consequence : mechanical damage  Diagnosis, Prevention

7. Strategy: To understand the link between causes and consequences to optimize: Diagnosis - Prevention - Treatment of Pathologies Joints 5 cm Normal force (N) 4 N Absence of the proteins cross-linkage Healthy diseased 200 s Compression Relaxation Time (s) Mechanical cause: Muscle-Ligaments system Rupture meniscus, ligament … Real stress Physico-chemical cause : Synovial fluid ~1 µm Acceptable stress Molecular assembling destruction Biological cause : Cartilage 3 causes  1 consequence : Wear of cartilage  Diagnosis, Prevention

8. Strategy To understand the link between causes and consequences to optimize: Diagnosis - Prevention - Treatment of Pathologies Vasculardesease Mechanical cause: blood pressure / elasticity of arteries Rupture d’anévrisme Real stress Physico-chemical cause : Interface blood / wall artery Blood non-Newtonian Interaction with the wall Lipid Précipitation + Ca++, pH  8  mineralization Acceptable stress Dumbell model Biological cause : endothelial wall Reactions of endothelial cells to mechanical stress  changing of wall mechanical properties 3 causes  1 consequence : Vascular Pathologies  Diagnosis, Prevention

9. Strategy To understand the link between causes and consequences to optimize: Diagnosis - Prevention - Treatment of Pathologies Target the treatments Mechanics Computer Aided Surgery Numerical simulation of endovascular treatment Correlation calicification / mechanical properties Physico-chemistry Antigen atheroma Polymeric layer Substances of contrast for MRI precocious detection Antibody Magnetic heart 5 nm Biology Bio actives surfaces for stents re-stenosis Polymeric layer + drug

10. 1er body 3ème body Mechanism 1er body 5 nm Interactions First body Thirdbody Methodology: Development of realistic experimental and numerical ex-vivo models! ex vivo in vivo

11. Mechanism Numerical simulation to understand the origin of the acoustical signals 20 cm Analysis of articular vibration Acoustical detection according to total applied forces

12. Mechanism 20 cm Individual prosthesis Mechanical influence on the stress/strain rate and distribution of varus/valgus deviation, stem size detection Goal: enhance clinical outcomes of THR to decrease the risk of revision surgery

13. Tribological Mechanisms (f) (a) (e) (b) (d) (c) Analysis of vibrations - touch Reproduce and measure vibrations produced at the contact Control of contact parameters Vibrations caused by rubbing, received by the mechano-receptor of the skin Test sample Linear guide Flexible joint Non-contactinglinearactuator Force transducer Accelerometer Tactile feeling influencing manipulation and sensory perception of the quality of an object

14. Skin mechanical properties Experimental characterisation Human skin Macro. Scale Micro. Scale Collagen Fibre orientations 1D tensile test Mechanical Properties Micro Structure Global & Local strains Main collagen fibre orientations • Nonlinear hyperelastic & softening behaviour • Main collagen fibre orientations Elastic modulus  Elastic modulus & Failure characteristics • Heterogeneous strain field Failure mechanism • 2 failure mechanisms  Heterogeneity rate, complete behaviour charact. • Image correlation method  Reducedispersion  More information • Adjustable experimental devices & measurement tools + • Link micro / macro

15. Skin mechanical properties Modelling Human skin Macro. Scale Micro. Scale Mechanical Properties Micro Structure 2 Scales Structural Constitutive Law • Nonlinear hyperelastic & softening law with failure  Few parameters with strong physical meaning FE Model • FE code adapted to large strains & softening behaviour  Elastic modulus variation with main fibre orientation  Heterogeneous stress & strain fields  Gradual failure of the tissue + Easy modelling/adaptation of other severely injured fibrous tissues

16. open repair endovascular repair Virtual surgery for Abdominal Aortic Aneurysm (AAA) Abdominal Aortic Aneurysm (AAA) normal aorta angiography angiography computer tomography

17. Soft tissue: mechanicalproperties Intima Média Adventice Artère 10.7MPa 9MPa 8.5MPa 0.9 3.4MPa 4.1MPa 3.7MPa 0.4 0.7MPa 0.4MPa 0.16MPa 0.1 0.1MPa 0.09MPa 0.01MPa 0.1 301KPa 505KPa 721KPa 0.09 56KPa 102KPa 162KPa 0.05 Intima Media Adventice Artery 10.7MPa 9MPa 8.5MPa 0.9 3.4MPa 4.1MPa 3.7MPa 0.4 0.7MPa 0.4MPa 0.16MPa 0.1 0.1MPa 0.09MPa 0.01MPa 0.1 301KPa 505KPa 721KPa 0.09 56KPa 102KPa 162KPa 0.05 Cartographie du module de Young et du coefficient de frottement en fonction du degré de calcification de différentes couches de l’aorte

18. Mechanical behaviour Elastin fibers mainly resisting Collagen fibers mainly resisting Z axis Aorta properties: homogenization Material: elastic, homogeneous and isotropic Orientation of collagen fibers

19. Patient 1 3D visualization of the guidewire and catheter navigation from the incision area to the neck of the aneurysm

20. Patient 1 3D visualization of the stent deployment

21. Interface and biological lubricant behavior 1. Local mechanical conditions of biological contacts 3. Mechanics and Physico-chemistry of the biological lubricants Lipidicbi-layers glass Use of markers: fluorescent lipids 0.5 nm Hydrogel Pockets of synovial gel 2. Mechanics and Physico-chemistry of biological tissues 0.5 µm + Friction Visualization Realistic Analysis of the bio-tribological functioning N v

22. Conclusions Future Research

23. Conclusions and Future Research LaMCoS - INSA Lyon Means of investigation LaMCoS Experimental  Numerical Mechanical  Physicochemistry  Biology Realistic ex vivo models Scientificcontext: bio mechanical and bio-tribological functioning LaMCoS contribution " Basic motive " of bio-lubrication Characterizations of biological interfaces and soft tissues Continue these scientific developments

24. Future Research To understand the link between causes and consequences To optimize: Diagnosis - Prevention - Treatment of Pathologies Security - Public health Tribological Simulators with high resolution (nm, pN) Physicochemical control Mechanicalcontrol Biochemical control: nutrition factors enzymes Biological control Mechanical control (mechanism): Understand the origin of mechanical disturbances Detection of damage - acoustics in vivo / Understanding ex vivo mechanical simulators Physicochemical control (third body) : Control of lubricants and interfaces: bio-mimetics Development of nano-physical techniques on tribological simulators Biological control (first body): Compensation of damage by simulation of the cell Mechanical-transducing Development of a bioreactor with mechanical loadings