BACKGROUND: Titanium oxides are known to be good hemocompatible, therefore they are suggested as coatings for blood contacting implants. But little is known about the influence of physical characteristics like crystal structure, roughness and electronic state on the activation of blood platelets and the blood clotting cascade. METHODS: Titanium oxide films were produced by metal plasma deposition and implantation in the form of rutile, crystalline and nanocrystalline anatase + brookite and amorphous TiO2. The redox potential was reduced by implantation of chromium ions, the Fermi level of the semiconductive oxide was shifted by ion implantation of the electron donor phosphorous. Hemocompatibility was determined by measuring the adhesion of blood platelets, their P-selectine expression, and of the blood clotting time on these samples. RESULTS: The crystalline titanium oxides had a slightly higher activation of the clotting cascade but lower platelet adhesion than nanocrystalline and amorphous titanium oxides. The surface roughness below 50 nm had no obvious effect. Both, implantation of phosphorous or chromium ions, strongly reduced the activation of the clotting cascade, but only the phosphorous implanted surface also showed a reduced platelet activation, whereas platelet adhesion and activation was strongly increased on the chromium implanted surfaces. CONCLUSION: Phosphorous doping of rutile TiO2 can increase its hemocompatibility, both concerning blood platelets and blood clotting cascade, but the biochemical mechanism has to be worked out.
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References
1.
1. Sánchez, J., Lundquista, P.B., Elgueb, G., Larssonb, R. and Olsson, P. (2002). Measuring the Degree of Plasma Contact Activation Induced by Artificial Materials , Thromb. Res., 105: 407-412 .
2.
2. Sanchez, J., Elgue, G., Riesenfeld, J. and Olsson, P. (1998). Studies of Adsorption, Activation, and Inhibition of Factor XII on Immobilized Heparin , Thromb. Res., 89: 41-50 .
4. Bernacca, G.M., Gulbransen, M.J., Wilkinson, R. and Wheatley, D.J. (1998). In Vitro Blood Compatibility of Surface-modified Polyurethanes , Biomaterials, 19: 1151-1165 .
5.
5. Broberg, M. and Nygren, H. (2001). Von Willebrand Factor, a Key Protein in the Exposure of CD62P on Platelets , Biomaterials, 22: 2403-2409 .
6.
6. Broberg, M., Eriksson, C. and Nygren, H. (2002). GpIIb/IIIa is the Main Receptor for Initial Platelet Adhesion to Glass and Titanium Surfaces in Contact with Whole Blood , J. Lab. Clin. Med., 139: 163-172 .
7.
7. Spijker, H.T., Bos, R., Busscher, H.J., van Kooten, T.G. and van Oeveren, W. (2002). Platelet Adhesion and Activation on a Shielded Plasma Gradient Prepared on Polyethylene , Biomaterials, 23: 757-766 .
8.
8. Hunt, B.J., Parratt, R., Cable, M., Finch, D. and Yacoub, M. (1997). Activation of Coagulation and Platelets is Affected by the Hydrophobicity of Artificial Surfaces , Blood Coagul. Fibrinolysis, 8: 223-231 .
9.
9. Lee, J.H., Khang, G., Lee, J.W. and Lee, H.B. (1998). Platelet Adhesion onto Chargeable Functional Group Gradient Surfaces , J. Biomed. Mater. Res., 40: 180-186 .
10.
10. Sefton, M.V., Sawyer, A., Gorbet, M., Black, J.P., Cheng, E., Gemmell, C. and Pottinger-Cooper, E. (2001). Does Surface Chemistry Affect Thrombogenicity of Surface Modified Polymers? , J. Biomed. Mater. Res., 55: 447-459 .
11.
11. Hehrlein, C., Zimmermann, M., Metz, J., Ensinger, W. and Kübler, W. (1995). Influence of Surface Texture and Charge on the Biocompatibility of Endovascular Stents , Coron. Artery Dis., 6: 581-586 .
12.
12. Vienken, J., Diamantoglou, M., Hahn, C., Kamusewitz, H. and Paul, D. (1995). Considerations on Developmental Aspects of Biocompatible Dialysis Membranes , Artif. Organs., 19: 398-406 .
13.
13. Santerre, J.P., ten Hove, P., VanderKamp, N.H. and Brash, J.L. (1992). Effect of Sulfonation of Segmented Polyurethanes on the Transient Adsorption of Fibrinogen from Plasma: Possible Correlation with Anticoagulant Behavior , J. Biomed. Mater. Res., 26: 39-57 .
14.
14. Grasel, T.G. and Cooper, S.L. (1989). Properties and Biological Interactions of Polyurethane Anionomers: Effect of Sulfonate Incorporation , J. Biomed. Mater. Res., 23: 311-338 .
15.
15. Porte-Durrieu, M.C., Aymes-Chodur, C., Betz, N. and Baquey, C. (2000). Development of “heparin-like” Polymers using Swift Heavy Ion and Gamma Radiation. I. Preparation and Characterization of the Materials , J. Biomed. Mater. Res., 52: 119-127 .
16.
16. Tsai, M.Y. and Lin, J.C. (2001). Surface Characterization and Platelet Adhesion Studies of Self-assembled Monolayer with Phosphonate Ester and Phosphonic Acid Functionalities , J. Biomed. Mater. Res., 55: 554-565 .
17.
17. Serruys, P.W., Emanuelsson, H., van der Giessen, W., Lunn, A.C., Kiemeney, F., Macaya, C., Rutsch, W., Heyndrickx, G., Suryapranta, H., Legrand, V., Goy J.J., Materne, P., Bonnier, H., Morice, M.C., Fajadet, J., Belardi, J., Colombo, A., Garcia, E., Ruygrok, P., de Jaegere, P. and Morel, M.A. (1996). Heparin-coated Palmaz-Schatz Stents in Human Coronary Arteries. Early Outcome of the BENESTENT-II Pilot Study , Circulation, 93: 412-422 .
18.
18. Eriksson, C. and Nygren, H. (2001). Polymorphonuclear Leukocytes in Coagulating Whole Blood Recognize Hydrophilic and Hydrophobic Titanium Surfaces by Different Adhesion Receptors and Show Different Patterns of Receptor Expression , J. Lab. Clin. Med., 137: 296-302 .
19.
19. Baurschmidt, P. and Schaldach, M. (1980). Alloplastic Materials for Heartvalve Prostheses , Med. Biol. Eng. Comput., 18: 496-502 .
20.
20. Chen, J.Y., Leng, Y.X., Tian, X.B., Wang, L.P., Huang, N., Chu, P.K. and Yang, P. (2002). Antithrombogenic Investigation of Surface Energy and Optical Bandgap and Hemocompatibility Mechanism of Ti(Ta+5)O2 Thin Films , Biomaterials, 23: 2545-2552 .
21.
21. Bolz, A. and Schaldach, M. (1990). Artificial Heart Valves: Improved Blood Compatibility by PECVD a-SiC:H Coating , Artif. Organs., 14: 260-269 .
22.
22. Zhang, F., Zheng, Z., Chen, Y., Liu, X., Chen, A. and Jiang, Z. (1998). In Vivo Investigation of Blood Compatibility of Titanium Oxide Films , J. Biomed. Mater. Res., 42: 128-133 .
23.
23. Huang, N., Chen, Y.-R., Luo, J.-M., Yi, J., Lu, R., Xiao, J., Xue,Z.-N. and Liu, X.-H. (1994). In Vitro Investigation of Blood Compatibility of Ti with Oxide Layers of Rutile Structure , J. Biomater. Appl., 8: 404-412 .
24.
24. Huang, N., Yang, P., Chen, X., Leng, Y., Zeng, X., Jun, G., Zheng, Z., Zhang, F., Chen, Y., Liu, X. and Xi, T. (1998). Blood Compatibility of Amorphous Titanium Oxide Films Synthesized by Ion Beam Enhanced Deposition , Biomaterials, 19: 771-776 .
25.
25. Li, J. (1993). Behaviour of Titanium and Titania-based Ceramics in vitro and in vivo , Biomaterials, 14: 229-232 .
26.
26. Liu, X.H., Zheng, Z.H., Zhou, Z.Y., Huang, N., Yang, P., Cai, G.J. and Chen, Y.R. (1996). Surface Modification of Titanium Based Biomaterials by Ion Beam , J. Biomater. Appl., 10: 330-337 .
27.
27. Murray, J.L. and Wriedt, H.A. (1990). O-Ti (Oxygen-Titanium), In: Massalski, T.B., Okamoto, H., Subramanian, P.R. and Kacprzak, L. (eds), Binary Alloy Phase Diagrams Materials Park, pp. 2924-2927, ASM International, Ohio .
28.
28. Song, S.-H., Wang, X. and Xiao, P. (2002). Effect of Microstructural Features on the Electrical Properties of TiO2 , Mater. Sci. Eng. B, 94: 40-47 .
29.
29. Kasuga, T., Kondo, H. and Nogami, M. (2002). Apatite Formation on TiO2 in Simulated Body Fluid , J. Crystal Growth, 235: 235-240 .
30.
30. Oyoshi, K., Sumi, N., Umezu, I., Souda, R., Yamazaki, A., Haneda, H. and Mitsuhashi, T. (2000). Structure, Optical Absorption and Electronic States of Zn+ Ion Implanted and Subsequently Annealed Sol-Gel Anatase TiO2 Films , Nucl. Inst. Meth. Phys. Res. B, 168: 221-228 .
31.
31. Attenberger, W., Thorwarth, G., Manova, D., Mändl, S., Stritzker, B. and Rauschenbach, B. (2001). Interface Properties of TiO2 on Si Formed by Simultaneous Implantation and Deposition of Titanium and Oxygen Ions , Surf. Coat. Techn., 142-144: 412-417 .
32.
32. Tsyganov, I., Maitz, M.F., Wieser, E., Prokert, F., Richter, E. and Rogozin, A. (2002). Structure and Properties of Titanium Oxide Layers Prepared by Metal Plasma Immersion Ion Implantation and Deposition , Surf. Coat. Techn., in press.
33.
33. Grunkemeier, J.M., Tsai, W.B. and Horbett, T.A. (1998). Hemocompatibility of Treated Polystyrene Substrates: Contact Activation, Platelet Adhesion, and Procoagulant Activity of Adherent Platelets , J. Biomed. Mater. Res., 41: 657-670 .
34.
34. Racher, A. (1998). LDH Assay, In: Doyle, A. and Griffiths, J.B. (eds), Cell and Tissue Culture: Laboratory Procedures in Biotechnology Chichester, pp. 71-75, John Wiley & Sons, New York, Weinheim .
35.
35. Sunny, M.C. and Sharma, C.P. (1991). Titanium-Protein Interaction: Changes with Oxide Layer Thickness , J. Biomater. Appl., 6: 89-98 .
36.
36. Nygren, H., Tengvall, P. and Lundstrom, I. (1997). The Initial Reactions of TiO2 with Blood , J. Biomed. Mater. Res., 34: 487-492 .
37.
37. Nygren, H., Eriksson, C. and Lausmaa, J. (1997). Adhesion and Activation of Platelets and Polymorphonuclear Granulocyte Cells at TiO2 Surfaces , J. Lab. Clin. Med., 129: 35-46 .
38.
38. Kawamoto, N., Mori, H., Terano, M. and Yui, N. (1997). Blood Compatibility of Polypropylene Surfaces in Relation to the Crystalline-Amorphous Microstructure , J. Biomater. Sci. Polym. Ed., 8: 859-877 .
39.
39. Kawamoto, N., Mori, H., Yui, N. and Terano, M. (1998). Mechanistic Aspects of Blood-contacting Properties of Polypropylene Surfaces - from the Viewpoint of Macromolecular Entanglement and Hydrophobic Interaction via Water Molecules , J. Biomater. Sci. Polym. Ed., 9: 543-559 .
40.
40. McAlarney, M.E., Oshiro, M.A. and McAlarney, C.V. (1996). Effects of Titanium Dioxide Passive Film Crystal Structure, Thickness, and Crystallinity on C3 Adsorption , Int. J. Oral Maxillofac. Implants, 11: 73-80 .
41.
41. (1997). In: Klein, J. and Horejsi, V. (eds), Complement and Complement Receptors, pp. 348-392, Blackwell Science, Immunology Oxford, Malden, MA .
42.
42. Clarotti, G., Schue, F., Sledz, J., Ait Ben Aoumar, A., Geckeler, K.E., Orsetti, A. and Paleirac, G. (1992). Modification of the Biocompatible and Haemocompatible Properties of Polymer Substrates by Plasma-deposited Fluorocarbon Coatings , Biomaterials, 13: 832-840 .
43.
43. Zingg, W., Neumann, A.W., Strong, A.B., Hum, O.S. and Absolom, D.R. (1981). Platelet Adhesion to Smooth and Rough Hydrophobic and Hydrophilic Surfaces Under Conditions of Static Exposure and Laminar Flow , Biomaterials, 2: 156-158 .
44.
44. Ward, C.A., Koheil, A., Johnson, W.R. and Madras, P.N. (1984). Reduction in Complement Activation from Biomaterials by Removal of Air Nuclei from the Surface Roughness , J. Biomed. Mater. Res., 18: 255-269 .
45.
45. Kalman, P.G., Ward, C.A., McKeown, N.B., McCullough, D. and Romaschin, A.D. (1991). Improved Biocompatibility of Silicone Rubber by Removal of Surface Entrapped Air Nuclei , J. Biomed. Mater. Res., 25: 199-211 .
46.
46. Edelman, E.R., Seifert, P., Groothuis, A., Morss, A., Bornstein, D. and Rogers, C. (2001). Gold-coated NIR Stents in Porcine Coronary Arteries , Circulation, 103: 429-434 .
47.
47. Thull, R., Trautner, K. and Karle, E.J. (1992). Modell zur Immunologischen Prüfung von Biomaterialien , Biomed. Tech. (Berl), 37: 162-169 .
48.
48. Thull, R. (2002). Physicochemical Principles of Tissue Material Interactions , Biomol. Eng., 19: 43 .
49.
49. Ellingsen, J.E. (1991). A Study on the Mechanism of Protein Adsorption to TiO2 , Biomaterials, 12: 593-596 .
50.
50. Lyman, D.J. (1991). Bulk and Surface Effects on Blood Compatibility , J. Bioact. Compat. Polym., 6: 283-295 .
51.
51. Grossmann, A. (1999). In: Michal, G. (Ed.), Blutgerinnung und Fibrinolyse, pp. 251-257, Spektrum, Akad. Verlag, Biochemical Pathways, Biochemie-Atlas Heidelberg .
52.
52. Bolz, A. and Schaldach, M. (1992). Physikalische Mechanismen der Festkörper-Protein-Wechselwirkung an der Phasengrenze a-SiC:H-Fibrinogen , Biomed. Tech. (Berl), 37: 244-253 .
53.
53. Rzany, A., Leistner, T., Steiner, J., Bolz, A. and Schaldach, M. (1998). Der Einfluss der elektronischen Oberflächeneigenschaften auf die Wechselwirkung zwischen Fibrinogen und Festkörpern , Biomed. Tech. (Berl), 43 Suppl: 388-389 .
54.
54. Rzany, A., Bayer, G., Bolz, A. and Schaldach, M. (1997). AFM-Untersuchung der festkörperinduzierten Blutgerinnung in Abhängigkeit von den Elektronischen Oberflächeneigenschaften , Biomed. Tech. (Berl), 42 Suppl: 43-44 .
55.
55. Coleman, D.L., Gregonis, D.E. and Andrade, J.D. (1982). Blood-Materials Interactions: The Minimum Interfacial Free Energy and the Optimum Polar/Apolar Ratio Hypotheses , J. Biomed: Mater. Res., 16: 381-398 .
56.
56. Galli, M., Sommariva, L., Prati, F., Zerboni, S., Politi, A., Bonatti, R., Mameli, S., Butti, E., Pagano, A. and Ferrari, G. (2001). Acute and Mid-term Results of Phosphorylcholine-coated Stents in Primary Coronary Stenting for Acute Myocardial Infarction , Catheter. Cardiovasc. Interv., 53: 182-187 .
57.
57. Iwasaki, Y., Mikami, A., Kurita, K., Yui, N., Ishihara, K. and Nakabayashi, N. (1997). Reduction of Surface-induced Platelet Activation on Phospholipid Polymer , J. Biomed. Mater. Res., 36: 508-515 .
58.
58. Welle, A., Grunze, M. and Tur, D. (1998). Plasma Protein Adsorption and Platelet Adhesion on Poly[bis(trifluoroethoxy)phosphazene] , J. Colloid Interface Sci., 197: 263-274 .
