Hemocompatibility of Surface Modified Si Incorporated Diamond-like Carbon Films R. K. Roy, S.-J. Park, H.-W. Choi, K.-R. Lee Future Technology Research Division, KIST, Seoul, Korea J. H. Kim, D. K. Han Biomaterials Research Center, KIST, Seoul, Korea J.-H. Shin Department of Radiology, Asan Medical Center, Seoul, Korea 4 th Int. Symp. Nano Structured Materials, KINTEX, Ilsan ( )

Vascular Stents Formation of blood clots  Restenosis Release of metal ions Hemocompatible and Hermetic Coating Clotted Artery

Surface Modification Biocompatible Coating : Heparin, PEG, DLC (Hepacoat, Phytis) Drug Release Coating : Antistenosis, Anticancer, Antibiotic (Cordis) Isotope Radiation Coating : Radiation therapy

Diamond-like Carbon Film Amorphous Solid Carbon Film Mixture of (sp 1 ), sp 2 and sp 3 Hybridized Bonds High Content of Hydrogen (20-60%) Properties –High Hardness and Excellent Tribological Properties –Smooth Surface with Optical Transparency –Chemical Inertness and Hemo-compatibility Heart valve Hard disk 2-D Analogy of the Structure

Diamond-like Carbon Film Amorphous Solid Carbon Film Mixture of (sp 1 ), sp 2 and sp 3 Hybridized Bonds High Content of Hydrogen (20-60%) Properties –High Hardness and Excellent Tribological Properties –Smooth Surface with Optical Transparency –Chemical Inertness and Hemo-compatibility Heart valve Hard disk

Si-DLC Film Potentiodynamic Polarization Water Contact Angle Measurement

Sl. No. References Hemocompatibility Improves by 1 Baier, Academic Press, New York, Critical surface tension of materials ~ 20-30dyne/cm 2 Akers, J.Colloid Interface Sci. 59 (1977) 461. Zone of biocompatibility 3 Ruckensten & Gourisanker, J. Colloid Interface Sci. 101 (1984) 436. Blood biomaterial interfacial tension of the order of 1-3 dyne/cm 4 Callow, International Biodeterioration & degradation, 34 (1994) 333. Surfaces having initial surface tension dyne/cm 5 Yu, Surf. Coat. Technol (2000) 484. Low blood biomaterial interfacial tension (8.5 dyne/cm) 6 Kwok, Diam. Rel. Mater. 14 (2005) 78. interfacial tension of about the same mag nitude as cell-medium interfacial tension (1-3 dyne/cm) Hemocompatibility and Surface Tension

Si-DLC Film Potentiodynamic Polarization Water Contact Angle Measurement

Schematic diagram of RF PACVD system. Film Preparation Film Deposition –C 6 H 6 + SiH 4 –Pressure : 1.33 Pa –Bias voltage : -400V –Film thickness : ~500nm –Si Concentration in the film : 2 at.% Surface Treatment –O 2, N 2, H 2, CF 4 –Pressure : 1.33 Pa –Bias voltage : -400V –10min

Energetics of Surface  Liquidαlαl βlβl γ lv (ergs/cm 2 ) Water Formamide

Surface Energy

XPS Anaysis

_ _ N1 : Si-N N2 : C=N

XPS Analysis Films Chemical bonds present on surface (XPS analysis) Si-DLCC=C, C-C, Si-C, Si-O Si-DLC (CF 4 plasma treated) C=C, C-C, C-CF n, Si-C, Si-O Si-DLC (N plasma treated) C=C, C-C, C-N, Si-N, Si-O Si-DLC (H plasma treated) C=C, C-C, Si-C, Si-O Si-DLC (O plasma treated) C=C, C-C, C-O, Si-O

Interfacial Tension with Human Blood α (dyne/cm) 1/2 β (dyne/cm) 1/2 Human Blood αβ Si-DLC5.4 ± ± 0.6 Si-DLC (CF 4 treated) 5.0 ± ± 0.5 Si-DLC (N 2 treated) 5.1 ± ± 0.3 Si-DLC (O 2 treated) 4.2 ± ± 0.1 Si-DLC (H 2 treated) 5.5 ± ± 0.4

aPTT Measurement Activated partial thromboplastin time (aPTT) determines the ability of blood to coagulate through the intrinsic coagulation mechanism. It measures the clotting time from the activation of the factor XII through the formation of fibrin clot. Incubation time : 1h in platelet poor plasma (PPP: 7x10 3 /  l) using fresh blood aPTT measurement system by Sysmex Instrument

Plasma Protein Adsorption The plasma protein adsorption tests were done by treating the samples with albumin (3mg/ml) and fibrinogen (0.2mg/ml) solution. The absorbances was measured by ELISA analysis method. Albumin Fibronogen

Plasma Protein Adsorption

Platelet Adhesion Uncoated SiN 2 treated Si-DLC H 2 treated Si-DLC O 2 treated Si-DLC After 2hr soaking in a platelet rich plasma (PRP: 1.05x10 5 /ml) of fresh blood.

Platelet Adhesion

Oxygen Plasma Treatment O 2 treated Si-DLC

XPS Analysis Films Chemical bonds present on surface (XPS analysis) Albumin/Fibrinogen ratio after 1h soaking Si-DLC (O plasma treated) C=C, C-C, Si-C, C=O, Si-O1.41 Si-DLC (CF 4 plasma treated) C=C, C-C, C-CF n, Si-C,1.02 Si-DLC (N plasma treated) C=C, C-C, C-N, Si-N0.99 Si-DLC (H plasma treated) C=C, C-C, Si-C0.92 Si-DLCC=C, C-C, Si-C0.70

Which is more significant? Films Chemical bonds on surface Wetting angle ( o ) α (dyne/cm) 1/2 β (dyne/cm) 1/2 a-Si:H (O plasma treated) Si-O7.5 ± ± ± 0.03 a-C:H (O plasma treated) C=C, C-C, C=O20.4 ± ± ± 0.15

Sl. No. References Hemocompatibility Improves by 1 Baier, Academic Press, New York, Critical surface tension of materials ~ 20-30dyne/cm 2 Akers, J.Colloid Interface Sci. 59 (1977) 461. Zone of biocompatibility 3 Ruckensten & Gourisanker, J. Colloid Interface Sci. 101 (1984) 436. Blood biomaterial interfacial tension of the order of 1-3 dyne/cm 4 Callow, International Biodeterioration & degra dation, 34 (1994) 333. Surfaces having initial surface tension dyne/cm 5 Yu, Surf. Coat. Technol (2000) 484. Low blood biomaterial interfacial tension (8.5 dyne/cm) 6 Kwok, Diam. Rel. Mater. 14 (2005) 78. interfacial tension of about the same magnitude as cell-medium interfacial tension (1-3 dyne/cm) Interfacial Tension?

Conclusions Hemocompatibility of Si-DLC film was improved by surface plasma treatment using oxygen. –Oxygen plasma treatment results in the highest surface energy with large polar component and the lowest interfacial energy with blood. –However, a definite relationship between the surface properties and the hemocompatibility is not found yet. Surface C=O bonds seem to play an important role in improving hemocompatibility.

Surface Energy Sl. No. CoatingsContact Angle Water (degree) Contact Angle Formamide (degree) Dispersive component of surface energy, Γ s d (nJ/cm 2 ) Polar Component of surface energy, Γ s p (nJ/cm 2 ) Total Surface Energy Γ s (nJ/cm 2 ) 1 DLC on Si SiDLC on Si SiDLC on Nitinol SiDLC on Si (CF 4 treated) SiDLC on Si (N 2 treated) SiDLC on Si (O 2 treated) SiDLC on Si (H 2 treated)