Princeton University. Adhsion and Interfacial Failure in Drug Eluting Stents

Princeton University Adhsion and Interfacial Failure in Drug Eluting Stents

Princeton University Background and Introduction Cardiovascular disease is the leading cause of death across the world It represents about 30% of all deaths Stents represent a life saving technology for arterioschlorosis Drug Eluting Stents (DES) reduce the possibility of clotting after stent insertion 2 1 Polymer Metal

Drug-Eluting Stents Drug 2 1 Polymer Metal rinceton University Marrey RV et al. (2006) Biomaterials 27:1988 2000

rinceton University AFM Adhesion Pull-Off Force Measurement Tip Radius ~ 59 nm Bare 316L Substrate RMS~0.4nm F pull-off = k (ΔZ) k -- Spring Constant (0.9 N/m for MPP contact tips) ΔZ -- Cantilever Deflection

rinceton University AFM Adhesion Pull-Off Force Measurement Silane coated tip on Parylene/Silane treated E-polished 316L substrate Pull-Off Force=30nm/div 1.22 div 0.9 N/m = 33 nn

rinceton University Pull-Off Force (nn) AFM Adhesion Pull-Off Force Measurement 800 700 622 600 500 400 300 200 100 34 115 306 46 48 stb316e btb316e pts316e sts316e stps316e ptps316e 0 Different Tip-Substrate Combination stb316e silane tip on bare 316L pts316e parylene tip on silane treated 316L stps316e silane tip on parylene/silane 316L (e - Electro-polished) btb316e - bare tip on bare 316L sts316e silane tip on silane treated 316L ptps316e payrlene tip on parylene/silane 316L

Parylene, Silane Silane/Parylene, Silane Parylene, Parylene Silane/Parylene, Parylene Parylene, Bare 316L Silane/Parylene, Bare 316L Adhesion Force (nn). Experiments: AFM 800 Parylene C Layer to Metal Substrate Interactions Wolf et al., J Biomed Mater Res A. (2008), Feb. 600 400 200 313 292 207 118 320 257 0 rinceton University Surface Pair (Surface 1, Surface 2) Surface Coating Coating Average Coupon rms Roughness (nm) Average Radius (nm) Coupon STD (nm) EP 316L 106 42 Radius STD (nm) Parylene C 370 31

Adhesion Theory R 1 1 R 1 R 1 1 R 2 R 2 F ad F R 1 2 12 (a) (b) (c) (d) Hert z JKR DMT Actual h 0 Johnson KL, Kendall K, Roberts AD (1971) Proc. R. Soc. London, Ser.A, 324, Derjaguin BV, Muller VM, Toporov YP (1975) J. Colloid Interface Sci., 53, 314. rinceton University

Adhesion Theory Johnson Kendall Roberts (JKR) model: describes well the contact area when the surface forces are short range in comparison to the elastic deformations they produce (i.e., compliant materials, strong adhesion forces, large tip radii) 3 2 F JKR R Derjaguin Muller Toporov (DMT): applies well in the case of longrange surface forces with an hertzian geometry (i.e., stiff materials, weak adhesion forces, small tip radii) General case rinceton University F ad F DMT 2 R F R Carpick RW, Ogletree DF, and Salmeron M (1999) J. Colloid Interface Sci., 211, 395. f R 2 0 2 K 1/3 ( ) 0.913ln(1 1.018 ) 2 F 0.267 0.767 2.000 0 h 0

Typical Force-Displacement Curve Extending Retraction 0.00 300.00 600.00 Z (nm) 464.60 Parylene/316L rinceton University Deflection (nm) 285 58 nm

Modeling AFM Adhesion Parylene/316L Adhesion Energy: f R 2 0 2 K 1/3 ( ) 0.913ln(1 1.018 ) F 2 0.267 0.767 2.000 0 h 0 R = 370 nm F ad = 320 nn rinceton University Lorentz Berthelot mixing rule: 1 h012 ( h01 h 2 02 )

Fracture Mechanics r Mode I Fracture Mechanics Problem: Mode I and Mode II stress intensity factors: K I and K II Strain energy release rate: Mode II Mode mixity: Unstable Crack: rinceton University Mode III

Force (N) rinceton University Experiments: Brazil nuts Energy release rate: P Loading phase: r 316L Parylene 2a Epoxy 120 316L 100 P 80 60 40 Wang and Suo, Acta Metall. Mater, 38 (7): 1279-1290; 20 0 0 0.01 0.02 0.03 0.04 0.05 0.06 Displacement (cm) Atkinson et al., Int J Fract Mech 18 (4): 279-291.

rinceton University Typical Fracture Surfaces: Parylene/Steel Sample #8 Figure 9 - Flat Not Marked Figure 10 - Notch Not Marked Parylene: Spectra found >1% Cl Figure11 Notch Marked Figure12 Flat Marked Glue: Spectra found Mainly C and O (Indicative of GLUE) Steel: Spectra found > 27% Fe (Indicative of steel)

Comparison of DMT models and Interfacial Fracture Experiments Interfacial Fracture Toughness Gc (J/m 2 ) rinceton University F DMT 2 R G G0 (1 tan 2 ) 3.5 3 2.5 2 1.5 1 0.5 0 Parylene Brazil Disk DMT 0 10 20 30 40 50 60 y

Atkinson Model Atkinson et al. (1982) Normalized Stress Intensity Factors and where Thus, load phase angle Energy release rate rinceton University Atkinson, C., Smelser, R.E., and Sanchez, J. Combined mode fracture via the cracked Brazilian disk test. International Journal of Fracture, 18(4), 1982, pp.279-291.

Fundamental Mechanism of Interfacial Fracture Evans and Hutchinson (1982) presented the row model No locking occurs Locking occurs rinceton University Evans, A.G., and Hutchinson, J.W. Effects of non-planarity on the mixed mode fracture resistance of biomaterial interfaces. Acta Metall, 37(3), 1989, pp.909-916.

Fundamental Mechanism of Interfacial Fracture rinceton University A zone model was proposed for improvement and thus EH /G0 when is large

Crack Surface Profile Measurement rinceton University Scanning Electron Microscopy (SEM) Images

rinceton University Material and Geometrical Parameters Stainless Steel Interface Parylene Interface Drug E=205GPa E=3GPa E=2.1~3.7GPa ν=0.3 v=0.28 v=0.27 G0=0.70N/m G0=0.19N/m L=500um L=1500um l=100um l=50um D=20um D=6um H=10um H=3um

rinceton University Comparison of Model Predictions Parylene

rinceton University Comparison of Model Predictions Silane- Parylene

rinceton University Comparison of Model Predictions Drug

rinceton University Summary and Concluding Remarks This class presents some examples of the applications of adhesion and fracture mechanics concepts to drug eluting stents Pull-off forces determined from AFM experiments on bi-material pairs (useful for ranking interfaces) Brazil disk specimens used to measure mode mixity dependence of interfacial fracture toughness Link established between molecular AFM measurements of pull-off force and surface energy The surface energy estimates are in good agreement with results from Brazil disk tests Trends of mode mixity fracture toughness from row/zone models in agreement with experiments

rinceton University Acknowledgments Cordis Company George Papendreou Cynthia Maryanoff Kurt Wolf Ting Tan Nima Rahbar Juan Meng Wanliang Shan

rinceton University Overview of Course Introduction to fatigue crack initiation and propagation Empirical fatigue models Fundamentals of fracture mechanics Toughening mechanisms Fundamentals of fracture brittle/ductile and mechanisms in different classes of materials Frontiers of fracture mechanics dental multilayers and biomedical stents