Hemocompatibility of Surface Modified Diamond-like Carbon Coatings R. K. Roy, M.-W. Moon, K.-R. Lee Future Technology 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 ABMC 2007, Tsukuba,

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

Required Surface Properties 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 Formation of blood clots  Restenosis Release of metal ions Hemocompatible and Hermetic Coating Clotted Artery

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

DLC is sufficiently hemocompatible? DLC film is not a specific material but a group of amorphous carbon thin films.  For each application, we need to optimize the property. Understanding of hemocompatibility of various DLC surfaces Si incorporated DLC films with modified surface

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

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

Surface modification of Si-DLC

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

Surface Energy

Polar Component and Wetting CF 4 plasma N 2 plasma As deposited H 2 plasma O 2 plasma Si wafer

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

XPS Anaysis

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N1 : Si-N N2 : C=N

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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

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

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

Platelet Adhesion Measurement Soaked for 60 min in PRP (1.5x10 15 /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

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 the Surface

Conclusions Hemocompatibility of Si-DLC film would be improved by surface treatment using nitrogen and oxygen plasma. –Large surface energy (large polar component) –Low interfacial energy with blood Aging of the surface with large surface energy should be carefully considered in characterizing their surface properties. Characterization should be done within 12 hours after the treatment.

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.