R. K. Roy, S.-J. Park, H.-W. Choi, K.-R. Lee Surface Properties and Hemocompatibility of 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 The 4th Korea-China Symposium on Biomaterials & Nano-Biotechnology, 2006. 10. 19-24, Jeju, Korea

Hemocompatible and Hermetic Coating Vascular Stents Clotted Artery Formation of blood clots  Restenosis Release of metal ions A stent is a metal tube that is inserted permanently into an artery. The stent helps open an clotted artery so that blood can flow through it. The cardiovascular implantation of stents is increasing day by day throughout the world. But the application of stents is largely limited by restenosis, occlusion and stent associated thrombosis. The main side effect with artery stents lies in its release of metal ions and thrombogenicity. It is thus necessary to coat metallic stents with suitable biomaterial that are hemocompatible, corrosion resistant and long lasting in human blood environment. Hemocompatible and Hermetic Coating

Surface Modification Biocompatible Coating : Heparin, PEG, DLC (Hepacoat, Phytis) Drug Release Coating : Antistenosis, Anticancer, Antibiotic (Cordis) Isotope Radiation Coating : Radiation therapy Many coated stents are already found in the market. Heparin are PEG are coated on the stent to meet the requirements of the hemocompatible surface. DLC coating can suppress the metal release in addition to the hemocompatiblility. This figure shows the DLC coated stent. More active concept is to use the drug release coating for antistenosis and treatment such as anticancer or antibiotic. There is also isotope radiation coating for radiation therapy. This presentation is about the DLC application for these purpose.

Diamond-like Carbon Film Amorphous Solid Carbon Film Mixture of (sp1), sp2 and sp3 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 2-D Analogy of the Structure Heart valve Hard disk

Diamond-like Carbon Film Amorphous Solid Carbon Film Mixture of (sp1), sp2 and sp3 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 Purpose of the present work Potentiodynamic Polarization Water Contact Angle Measurement

Hemocompatibility and Surface Tension Sl. No. References Hemocompatibility Improves by 1 Baier, Academic Press, New York, 1970. 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 20-30 dyne/cm 5 Yu, Surf. Coat. Technol. 128-129 (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)

Si-DLC Film Potentiodynamic Polarization Purpose of the present work Potentiodynamic Polarization Water Contact Angle Measurement

Film Preparation Film Deposition Surface Treatment C6H6 + SiH4 Pressure : 1.33 Pa Bias voltage : -400V Film thickness : ~500nm Si Concentration in the film : 2 at.% Surface Treatment O2, N2, H2, CF4 10min Schematic diagram of RF PACVD system.

Energetics of Surface q Liquid αl βl γlv (ergs/cm2) Water 4.67 7.14 72.8 Formamide 6.28 4.32 58.2

Surface Energy

XPS Anaysis

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

_ _

Chemical bonds present on surface XPS Analysis Films Chemical bonds present on surface (XPS analysis) Si-DLC C=C, C-C, Si-C, Si-O (CF4 plasma treated) C=C, C-C, C-CFn, Si-C, Si-O (N plasma treated) C=C, C-C, C-N, Si-N, Si-O (H plasma treated) (O plasma treated) C=C, C-C, C-O, Si-O

Interfacial Tension with Human Blood α (dyne/cm)1/2 β Human Blood 3.3 6.0 α β Si-DLC 5.4 ± 0.5 3.3 ± 0.6 (CF4 treated) 5.0 ± 0.4 2.0 ± 0.5 (N2 treated) 5.1 ± 0.2 5.5 ± 0.3 (O2 treated) 4.2 ± 0.1 7.3 ± 0.1 (H2 treated) 3.5 ± 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: 7x103/ml) 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. Fibronogen Albumin

Plasma Protein Adsorption

Platelet Adhesion After 2hr soaking in a platelet rich plasma (PRP: 1.05x105/ml) of fresh blood. Uncoated Si N2 treated Si-DLC H2 treated Si-DLC O2 treated Si-DLC

Platelet Adhesion

Oxygen Plasma Treatment O2 treated Si-DLC

Interfacial Tension? Sl. No. References Hemocompatibility Improves by 1 Baier, Academic Press, New York, 1970. 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 20-30 dyne/cm 5 Yu, Surf. Coat. Technol. 128-129 (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)

XPS Analysis

Which is more significant? Films Chemical bonds on surface Wetting angle (o) α (dyne/cm)1/2 β a-Si:H (O plasma treated) Si-O 7.5 ± 1.3 4.1 ± 0.02 7.4 ± 0.03 a-C:H C=C, C-C, C=O 20.4 ± 2.5 4.5 ± 0.11 7.0 ± 0.15

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 yet evident. Surface C=O bonds seem to play an important role in improving hemocompatibility.

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