Hemocompatibility of Plasma Treated Si Incorporated Diamond-like Carbon Films R. K. Roy, M.-W. Moon, K.-R. Lee Future Convergence Research Laboratories, KIST, Seoul, Korea D.K. Han Biomaterials Research Center, KIST, Seoul, Korea J.-H. Shin Department of Radiology, Asan Medical Center, Universtiy of Ulsan, Korea A.Kamijo Univ. Tokyo Hospital, Tokyo, Japan T. Hasebe Tachikawa Hospital, Keio University, Tokyo, Japan ICMCTF 2008, San Diego, USA

Requirements for Bioimplants 1.Should not cause infections 2.Prevent uncontrolled cell growth 3.Maintain their integrity inside the body 4.Interact in a controllable way with the biological environment 5.Avoid formation of debris Requirements for Bioimplants 1.Should not cause infections 2.Prevent uncontrolled cell growth 3.Maintain their integrity inside the body 4.Interact in a controllable way with the biological environment 5.Avoid formation of debris Surface Properties Bioimplant Materials

DLC for biomaterials Biological Compatibility –Nontoxic, Noncarcinogenic, Noninflammatory Chemical Compatibility –Corrosion Resistance Mechanical Compatibility –Surface Hardness, Wear Resistance Diamond-like Carbon : as a Strong Candidate Coating

Vascular Stents Suppress the formation of blood clots Prevent the release of metal ions Clotted Artery Hemocompatible and Hermetic Coating

DLC Coated Blood Contacting Implants Carbofilm TM by Sorin Biomedica, Inc.

The present work Systematic study on the effect of surface properties on the hemocompatibility. Plasma treatment of Si-DLC coating Characterization of the surface –Wetting behavior –Surface chemical bonds Hemocompatibility tests –Protein adsorption (Albumin/Fibrinogen ratio) –Activated Partial Thromboplastin time –Platelet adhesion and activation

Si-DLC Film Potentiodynamic Polarization in Saline Solution Thin Solid Films, 475, (2005). J. Biomed. Mater. Res. A in press (2007).

Schematics 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

Surface modification of Si-DLC

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

Surface Energy

Interfacial Tension with Human Blood α (dyne/cm) 1/2 β (dyne/cm) 1/2 Human Whole 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

XPS Anaysis

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

XPS Anaysis Si-DLCSi-DLC (CF 4 ) Si-DLC (O 2 )

Si-DLCSi-DLC (N 2 ) XPS Anaysis

Plasma Protein Adsorption Better hemocompatibility can be expected on the surface with higher ratio of albumin/fibrinogen adsorption. ELISA analysis after treating the samples with albumin (3mg/ml) and fibrinogen (0.2mg/ml) solution.

aPTT Measurement Activated partial thromboplastin time (aPTT) determines the ability of blood to coagulate through the intrinsic coagulation mechanism. The longer aPTT time is obtained on better hemocompatible surface. Soaking for 60min in platelet poor plasma (PPP: 7x10 3 /  l) using human whole blood from healthy volunteer.

Platelet Adhesion Measurement Soaked for 60 min in PRP (1.5x10 5 /ml) from human whole blood from healthy volunteer. Adherent platelet are fixed and dehydrated for observation under OM and SEM.

Platelet Activation Goodman and Allen et al. On a-C:H surface Lose discoid shape Develope thin pseudopodia Become large, spiny sphere covered by pseudopodia Fully spread

Platelets on Si-DLC

Platelets on Si-DLC (N 2 )

Platelet on Si-DLC (O 2 )

Nitrogen or Oxygen Plasma Treatment

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

Which surface bond is significant?

Conclusions Hemocompatibility of Si-DLC film was improved by the surface treatment using nitrogen and oxygen plasma. –Large surface energy (large polar component) –Low interfacial energy with blood Both C-O and Si-O bonds on the plasma treated Si- DLC surface play a significant role in improving the hemocomptatibility. R. K. Roy et al,Diam. Rel. Mater (2007). Submitted to Acta Biomater. (2008).

Acknowledgement Financial Support from 'Center for Nanostructured Materials Technology' under '21st Century Frontier R&D Programs' of the Ministry of Science and Technology of Korea (code #: 06K ), and Taewoong Medical Co. Ltd.