1. Effect of hemocompatibility on the surface properties of Si incorporated diamond like carbon films. R. K. Roy*, S. J. Park*, K.-R. Lee*, D. K. Han**, J.-H. Shin+, *Future Technology Division, Korea Institute of Science and Technology **Biomaterials Research Center, Korea Institute of Science and Technology, +Dept. Radiology, Asan Medical Center

2. Contents: 1. Introduction 2. Experimental 3. Results and Discussion: Surface energetics relation Wettability Blood biomaterial interfacial tension Activated partial thromboplastin time (aPTT) Protein adsorption tests Platelet adhesion and activation XPS analysis 4. Conclusion

3. 1. Introduction Heart valve A medical device in cardiovascular application faces the following problems: Thrombogenicity : formation of blood clots Cytotoxity : release of metal ions Stability in long term use: delamination and spallation during compressive and tensile forces of medical implants In this respect, diamond like carbon (DLC) has emerged as a promising coating material for cardiovascular application due to its superior tribological, inert and hemocompatible properties. Improved hemocompatibility is denoted by higher albumin/ fibrinogen ratio higher clotting times low platelet adhesion and activation To get rid of delamination and improve hemocompatibility, it is necessary to dope the surfaces of biomaterials with certain elements use an interlayer which improves its adhesive properties

4. 2. Experimental Schematic diagram of RF PACVD system. Coatings : Si incorporated DLC films. Synthesis method: Capacitively coupled rf plasma assisted chemical vapor deposition. Precursor gases : Benzene, silane. Substrates : Si, nitinol. Bias voltage : - 400 V System pressure : 1.33 Pascal Deposition time : 12 mins Ar cleaning : - 400 V, 0. 49 Pa, 15 mins. Surface modification: treating the Si incorporated DLC films with plasma of various gases like O, N, H and carbon tetrafluoride at - 400 V, 1.33 Pa, 10 mins. Interlayer: Si of thickness 5 nm to ensure better adhesion.

5. Young’s equation: where, θ is the contact angle between liquid and solid, are the free energies of the liquid and solid against their saturated vapor, is the free energy of the interface between liquid and solid, is the equilibrium pressure of adsorbed vapor of the liquid on the solid. where the superscript d and p refer to the dispersion and polar force components. (1) (2) (3) (4) (5) Surface Energetics Relations: where,,,, 3. Results and Discussion

6. Wettebility: Water contact angles of various surfaces: Liquid αlαl βlβl γ lv (ergs/cm 2 ) Water4.677.1472.8 Formamide6.284.3258.2 Coatings/ substrates Water contact angle (degree) Formamide contact angle (degree) O 2 treated SiDLC13.4 ± 1.35.0 ± 1.2 Si35.3 ± 2.712.0 ± 1.5 N 2 treated SiDLC42.7 ± 3.710.2 ± 1.3 H treated SiDLC67.2 ± 1.845.7 ± 1.4 SiDLC70.1 ± 3.049.5 ± 1.4 Nitinol76.6 ± 1.151.2 ± 0.7 CF 4 treated SiDLC88.4 ± 2.968.0 ± 0.5 Coatings αβ SiDLC5.4 ± 0.53.3 ± 0.6 SiDLC (CF 4 treated)5.0 ± 0.42.0 ± 0.5 SiDLC (N 2 treated)5.6 ± 0.25.2 ± 0.3 SiDLC (O 2 treated)4.2 ± 0.17.3 ± 0.1 SiDLC (H 2 treated)5.5 ± 0.33.5 ± 0.4

7. Surface energy of plasma treated Si incorporated DLC films: α (dyne/cm) 1/2 β (dyne/cm) 1/2 Human blood3.36.0 Human Fibrinogen4.976.35 Human serum albumin5.65.8 CoatingsTotal Surface Energy (nJ/cm 2 ) SiDLC39.7 ± 8.9 SiDLC (CF 4 treated)29.1 ± 5.8 SiDLC (N 2 treated)58.8 ± 6.1 SiDLC (H 2 treated)42.1 ± 6.0 SiDLC(O 2 treated)71.0 ± 1.1 Interfacial tensions between the implant (phase 1) and blood plasma (phase2) are given by: (6)

8. Activated Partial Thromboplastin Time (aPTT) The aPTT determines the ability of blood to coagulate through the intrinsic coagulation mechanism. It measures the clotting time from the activation of factor XII through the formation of fibrin clot. Incubation time: 30 mins and 1 hour in platelet poor plasma (PPP). A higher aPTT was noted in case of O plasma treated SiDLC films.

9. Plasma Protein Adsorption: Incubation time: 5 mins, 60 mins. The plasma protein adsorption tests were done by treating the samples with albumin and fibrinogen solution and measuring the absorbances through ELISA (Enzyme linked immunosorbent assay) analysis. The O and carbon tetraflouride plasma treated SiDLC films showed increased rate of albumin adsorption with time, while H plasma treated SiDLC films minimized rate of fibrinogen adsorption.

10. Platelet Adhesion and Activation: Si SiDLC (N treated) Incubation time in fresh human platelet rich plasma (PRP): 2 hours SiDLC (H treated) SiDLC (O treated) These results show that the adherence and activation of platelets is less in case of O and H plasma treated SIDLC films, compared to N plasma treated SiDLC films and Si substrate.

11. X-Ray Photoelectron Spectroscopy (XPS) studies: Bonding structure of carbon and fluorine show low polarizability, which gives rise to the low surface energy and increased hydrophobicity of carbon tetrafluoride treated SiDLC films. Si-O and C-N bonds are polar in nature, which results in higher polar component in the surface energy of O and N plasma treated SiDLC films. C-C bonds are present in all the films. F-F, C-N and Si-O bonds are seen on the surface of carbon tetraflouride, N and O plasma treated SiDLC films.

12. 4. Conclusions: The plasma treatment of the Si incorporated DLC films with various gases like N,O,H and carbon tetrafluoride has a considerable effect on its hemocompatibility and surface property. The O plasma treated SiDLC films have shown higher aPTT, higher albumin adsorption and minimized platelet adhesion and activation. The H plasma treated SiDLC films have reduced fibrinogen adsorption. The XPS studies revealed the presence of C-N, Si-O and F-F bonds in case of N,O and carbon tetrafluoride treated SiDLC films. The oxygen and H plasma treated SiDLC films can serve as effective coating on endovascular SMART nitinol stents.