1. Diamond-like Carbon Coating for Bio-medical Implant Materials Kwang-Ryeol Lee Future Technology Research Division Korea Institute of Science and Technology krlee@kist.re.kr http://diamond.kist.re.kr/DLC

2. Acknowledgement Dr. R. Hauert (EMPA, Switzerland) for valuable discussion and providing me the presentation materials on this issue. Prof. Jeong-Ku Kim (SKKU, Korea) for corrosion test in body fluid condition Prof. In-Seop Lee (Yonsei Univ., Korea) for tribological test of DLC coated Ti alloys in body fluid Prof. Hyeonee Kim (SNU, Korea) for cell attachment and hemocompatbility test Prof. R. Wang (UBC, Canada) for mechanical stability test Mr. Sejun Park, Mr. Heon-Woong Choi and Ms. Youngjin Lee Financial Support from Ministry of Science and Technology of Korea

3. 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

4. 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

5. Contents 1.Introduction to DLC 2.Blood Contacting Applications Stents, Heart valves, Flow Accelerators 3.Load Bearing Applications Hip Joints, Knee Joints, Artificial Disk 4.Summary and Technical Issues

6. Diamond-like Carbon : DLC Amorphous Solid Carbon Film Mixture of sp 1, sp 2 and sp 3 Hybridized Bonds High Content of Hydrogen (20-60%)

7. t-aC sp 2 H sp 3 DLC No film diamond graphite Polymer-like Graphitic t-aC:H DLC: A Group of Carbon Mat’l

8. Properties of Solid Carbon PropertyDiamondDLCGraphite Density (g/cm 3 )3.511.8 – 3.62.26 Atomic Number Density (Mole/cm 3 ) 0.30.2 – 0.30.2 Hardness (Kgf/mm 2 )100002000 - 8000500 Friction Coeff.0.050.03 – 0.20.1 Refractive Index2.421.8 – 2.62.15 – 1.8 TransparencyUV-VIS-IRVIS-IROpaque Resistivity (  cm) >10 16 10 10 - 10 13 0.2 – 0.4

9. Applications of DLC VCR Head Drum Wrist Pin Hard Disk & Slider CD/DVD Mold Spacer Tool Form Die Digital VCR Tape Razor Blade

10. Contents 1.Introduction to DLC 2.Blood Contacting Applications Stents, Heart valves, Flow Accelerators 3.Load Bearing Applications Hip Joints, Knee Joints, Artificial Disk 4.Summary and Technical Issues

11. Blood Contacting Applications Heart valves, Stents, Blood pumps etc. - Surface has to prevent thrombus formation and restenosis Adsorption of proteins Increased platelet adhesion Platelet activation and aggregation Formation of a thrombus Thrombus on a mechanical heart valve (courtesy of RWTH-Aachen) albumin/fibrinogen ratio Steps for Thrombus formation

12. Protein Adsorption on DLC a high ratio of albumin/fibrinogen low number of adhering platelets low tendency of thrombus formation 0 0.2 0.4 0.6 0.8 1 1.2 1.4 TiTiNTiCDLCsilicone elastomer PMMACN Albumin / Fibrinogen Ratio Jones et al. Dion et al. Cui et al. Albumin/fibrinogen ratio for different surfaces.

13. Excellent Hemocompatibility Clotting Time Measurement On glass On DLC

14. Excellent Hemocompatibility Blood platelets deposited on different surfaces as a function of exposure time. DLC coated accelerator PC coated accelerator

15. DIAMOND AS® Stent - Reduce thrombus formation - Prevent Cr, Ni release from 316 L steel DLC Coated Stents

16. Potentiodynamic Polarization

17. DLC Coated Stents

18. Evolution of Coating Failure (a) (b) (c) (d) (a) (b) (c) (d)

19. CARBOFILM™ made by PVD using a pyrolytic turbostratic carbon target. Probably it is a-C. Chrome-cobalt alloy cage, coated with CARBOFILM™ Problems: Wear in hinges, Hemocompatibility DLC Coated Heart Valves etc. Titanium alloy coated with DLC Products under development by Cardio Carbon Company Ltd. Carbofilm TM by Sorin Biomedica, Inc.

20. Contents 1.Introduction to DLC 2.Blood Contacting Applications Stents, Heart valves, Flow Accelerators 3.Load Bearing Applications Hip Joints, Knee Joints, Artificial Disk 4.Summary and Technical Issues

21. Polyethylene wear debris is the main factor limiting the lifetime of the implants Aseptic loosening, wear debris initiates inflammatory response, leading to osteoclast cells activation resulting in bone resorption DLC shows in atmosphere a low wear and also low friction coefficients against most materials DLC coated femoral heads for low wear ? DLC slides against its own transfer layer and only DLC is worn at a very low wear rate, whereas the softer partner surface will not be worn Load Bearing Implants V. Saikko et al., Biomaterials 22 (2001) 1507 Polyethylene wear debris

22. DLC Coating on Femoral Ball RF Power Cathode

23. In vitro Wear Test Pin on Disk DLC/UHMWPE (literature overview) Hip joint simulator (Lappalainen, Finnland) Pin on Disk Lubrication: - air - dest. water - 1wt% NaCl in water reduction of UHMWPE wear Hip joint simulator Lubrication: - diluted calf serum - synovial fluid no change in UHMWPE wear To be clinically relevant, tribological investigations on DLC/UHMWPE require: - Adequate tribological setup - Adequate lubricant

24. In vitro Test Hip joint simulator Lubrication: - diluted calf serum - synovial fluid Characterize surface Texture single scratches increase the wear rate of UHMWPE by a factor of 30-70 Tribological setup Lubrication Surface quality phospholipids, adsorbed on the surfaces, strongly influences the tribological behavior and may take part in tribochemical reactions J. Fisher et al., J. of Engineering in Medicine 209 (1995) 263 S.C. Scholes et al., Phys. Med. Biol. 45 (2000) 372 V. Saikko, T. Ahlroos, Wear 207 (1997) 86 Pin-on-Disk setup leads to clinically non relevant results

25. In vitro Test (only a few papers found) Lappalainen:Shi: Tiainen: 2003 2003 2001 ta-C/ta-C DLC/stainless steel ta-C/ta-C hip simulatorPoD PoD / hip simulator bovine serumbovine blood serum NaCl-water <10 -4 mm 3 /year50x less than st./st. 100x less than Al 2 O 3 /Al 2 O 3 promising resultquestionable setup questionable lubricant promising result Ref: steel/UHMWPE: 20-60 mm 3 /year (wear particles) steel/steel: 1-5 mm 3 /year (future allergies) ceramic/ceramic: 10 -2 mm 3 /year (can only be replaced by ceramic) R. Lappalainen et al., J. Biomed. Mater. Res. 66B (2003) 410-413 B. Shi et al., Wear 255 (2003) 1015-1021 V.-M. Tiainen, Diamond Relat. Mater. 10 (2001) 153-160 DLC/DLC or DLC/metal

26. Hip Joints: in vivo Test G. Taeger et al., Mat.-wiss. u. Werkstofftech. 34 (2003) 1094 101 patients DLC/PE 101 patients Al 2 O 3 /PE 8.5 year’s follow-up 50% of DLC/PE failed DLC/PE Al 2 O 3 /PE Retrieved DLC-head: Numerous pits revealing the metallic substrate, severe PE wear

27. Adhesive Wear in Body Fluid 200 ㎛

28. Shoulder-joint, the Ti-alloy ball coated with DLC (carbioceram™) ankle-joint, AISI Z5 CNMD 21 steel coated with DLC (carbioceram™) knee-joints coated with DLC (carbioceram™) No medical follow-up on these products found DLC Coated Artificial Joints

29. Failure Case (Knee Joint) ”Diamond Rota Gliding” DLN/UHMWPE knee- joints have been sold (without the necessary tests and permission) by Implant Design AG in 2001. Dylyn®, DLN (Diamond-like Nanocomposite) produced by Beckaert. The implanted joints showed increased wear and partial coating delamination and had to be replaced. Additionally, residual coating on the upper side of the implant was held responsible for the inadequate bone ingrowth. In July 2001 the implantation of this knee joint was forbidden by the Swiss Federal Office of Public Health (SFOPH). www.swissmedic.ch

30. Summary DLC film is not a specific materials but a group of amorhpous carbon materials Blood Contacting Applications –Good hemocompatibility –DLC Coated stents, heart valves, blood pumps are now available in the market. Artificial Joints Application –Needs an improved test method to obtain clinically relevant results. –DLC/DLC or DLC/metal combinations show more promising results than other combinations.

31. Technical Issues Careful consideration on the DLC film itself is required, because the DLC film is not a specific material. Stability of DLC coating in body fluid condition is one of the most critical issues for the biomedical applications. Stents –Stability of the coating with respect to the plastic deformation –Interface design would be helpful to increase the reliability. Artificial Joints –Characterization of the coating under an adequate test condition Does it really reduce the PE debris? Is it possible to have new design such as DLC/DLC or DLC/metal? –Stability of the coating during sliding in body fluid condition –Need tight control of the substrate surface

32. Diamond-like Carbon Coating for Bio-medical Implant Materials Kwang-Ryeol Lee Future Technology Research Division Korea Institute of Science and Technology krlee@kist.re.kr http://diamond.kist.re.kr/DLC

33. Cells in contact with DLC Many in vitro experiments with different cell types (macrophages, fibroblasts, human embryo kidney 293 cells, ML-1 cells, osteoblasts etc. ) - good growth rate - good viability - no morphological changes - no cellular damage - no inflammatory reactions - no cytotoxicity DLC may be expected to be biocompatible in vivo. Cell viability on control and DLC-coated plastic dished for ML-1 cells [L. Lu, M.W. Jones, R.L.C. Wu, Bio-Med. Mater. Eng. 3 (1993) 223].

34. Cell Growth Behavior Proliferation Differentiation 3 days 10 days (HOS: Human Osteo-sarcoma)

35. Protein adsorption on Ti-DLC Adsorption of human plasma proteins on a-C:H/Ti Chromatographic analysis of the proteins. Molecular weight marker is indicated on the left side. 184 kD 115 kD 86.3 kD 61.5 kD 50.8 kD 37.6 kD 25.4 kD Plasma GlasTi231370 a-C:H, at% Ti Molecular weight Tunable protein adsorption between Ti and DLC by the Ti concentration in Ti-DLC.

36. a-C:H a-C:H/3% V a-C:H/7.4% V a-C:H/15% V after 10 days in vitro BMC on V-DLC Tunable poisoning: Poisoning of the BMC cells due to vanadium dissolution out of the V-DLC film 300 µ m