Active Response of Smooth Muscle and Arterial Tissue to Stenting

Transcription

1 Active Response of Smooth Muscle and Arterial Tissue to Stenting O Connor, C., Reynolds, N., Nolan, D., McGarry, J.P. Department of Mechanical and Biomedical Engineering, NUI Galway 21 th April 2015

2 Artery Composition [1] Holzaphel et al, Journal of Elasticity. 61:1-48, 2001.

3 Artery Composition Effect of increased arterial stiffness on smooth muscle cells? In-stent restenosis at 1 year 1 [1] Holzaphel et al, Journal of Elasticity. 61:1-48, [2] Farooq et al,, Circ Cardiovasc Interv. 4: , 2011.

4 Mechanical Behavior of Cells 20 µm [3] Reynolds et al, Biomaterials. 35: , 2014.

5 Mechanical Behavior of Cells Myosin Head Online: Actin Filament 20 µm [3] Reynolds et al, Biomaterials. 35: , 2014.

6 Computational Interpretation of Dynamic Force Measurement Model Description (Stress fibre activation Level, η) Signal Induced Formation

7 Computational Interpretation of Dynamic Force Measurement Model Description (Stress fibre activation Level, η) Myosin Head Actin Filament Signal Induced Formation Online:

8 Computational Interpretation of Dynamic Force Measurement Model Description (Stress fibre activation Level, η) Tension, T Signal Induced Formation Shortening Velocity

9 Computational Interpretation of Dynamic Force Measurement Model Description (Stress fibre activation Level, η) Tension, T Signal Induced Formation Shortening Lengthening Velocity

10 Computational Interpretation of Dynamic Force Measurement Model Description Tension, T Signal Induced Formation Shortening Lengthening Velocity Tension Reduction [4] Kolega et al, J Cell Biol. 102: , [5] Franke et al, Nature. 81:570-80, [6] Warshaw et al, J Cell Biol. 111:453-63, 1990.

11 Computational Interpretation of Dynamic Force Measurement Model Description Tension, T Signal Induced Formation Shortening Lengthening Velocity Tension Reduction [7] Deshpande et al, P R Soc A. 463: , 2007.

12 Computational Interpretation of Dynamic Force Measurement Model Description [7] Deshpande et al, P R Soc A. 463: , 2007.

13 Computational Interpretation of Dynamic Force Measurement Model Description [7] Deshpande et al, P R Soc A. 463: , 2007.

14 Implementation Active Stress Fibre Model [8] Ronan et al, J Mech Behav Biomed Mater. 14:143-57, 2012.

15 Implementation Active Stress Fibre Model [8] Ronan et al, J Mech Behav Biomed Mater. 14:143-57, 2012.

16 Implementation Active Stress Fibre Model [8] Ronan et al, J Mech Behav Biomed Mater. 14:143-57, 2012.

17 Implementation Active Stress Fibre Model Passive Cytoplasm Material Neo-Hooke hyperelastic: [8] Ronan et al, J Mech Behav Biomed Mater. 14:143-57, 2012.

18 Implementation Active Stress Fibre Model Passive Cytoplasm Material Neo-Hooke hyperelastic: [8] Ronan et al, J Mech Behav Biomed Mater. 14:143-57, 2012.

19 Implementation Active Stress Fibre Model Passive Cytoplasm Material Neo-Hooke hyperelastic: [8] Ronan et al, J Mech Behav Biomed Mater. 14:143-57, 2012.

20 Collagen Gel Contraction Collagen gel contraction due to cardiac fibroblasts Day 0 Day 8 [9] Willie et al, Ann Biomed Eng. 34: , 2006.

21 Cellular Contraction Contraction of Collagen Microdroplets 1mm [10] Moraes et al, Biomaterials. 34: , 2013.

22 Cellular Contraction Simple volumetric contraction [8] Ronan et al, J Mech Behav Biomed Mater. 14:143-57, [10] Moraes et al, Biomaterials. 34: , 2013.

23 Volumetric Deformation of a Cube ΔL/L Bulk modulus, K (kpa)

24 Volumetric Deformation of a Cube ΔL/L SF Density, η Bulk modulus, K (kpa) Bulk modulus, K (kpa)

25 Volumetric Deformation of a Cube ΔL/L Decreasing k v SF Density, η Decreasing k v Bulk modulus, K (kpa) Bulk modulus, K (kpa)

26 Arterial Model P Diastole Pressure: 120 mmhg 80 mmhg

27 Arterial Dilation and Contraction during Systole and Diastole Compliant Artery

28 Arterial Dilation and Contraction during Systole and Diastole Compliant Artery Stiff Artery

29 Artery Contraction during Diastole Radius Reduction, r (mm) E = 90 kpa (Compliant) E = 130 kpa E = 200 kpa E = 450 kpa (Stiff) Diastole time, t (seconds)

30 Hoop Stress Fibre Evolution during Diastole η hoop Compliant Artery

31 Hoop Stress Fibre Evolution during Diastole η hoop η hoop Compliant Artery Stiff Artery

32 Hoop Stress Fibre Evolution during Diastole η hoop η hoop Compliant Artery Stiff Artery

33 Hoop Stress Fibre Evolution during Diastole Hoop SF Activation Level, η hoop Diastole time, t (seconds) E = 450 kpa E = 200 kpa E = 130 kpa E = 90 kpa

34 Conclusions Passive material stiffness significantly influences stress fiber remodeling. Smooth muscle stress fibers are more highly activated in stiffer arteries due to lower rate of radius reduction during diastole. Stent deployment will result in an artificial stiffening of the artery wall and will result in increased stress fiber activation. This may be an important factor in development of in-stent restenosis.

35 Acknowledgements Dr. Patrick McGarry s Group Elizabeth-Anne Gallagher Fiona Griffin Shane Heavey Eoin McEvoy David Nolan Brian O Reilly Noel Reynolds Science Foundation Ireland (SFI-12/IP/1723) Biomedical Engineering, NUI Galway