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Metal-ion release from titanium and TiN coated implants in rat bone*
NOMB
Nuclear Instruments and Methods in Physics Research B79 (1993) 421-423 North-Holland
Beam Intemctions with Materials&Atoms
Metal-ion release. from titanium and TiN coated implants in rat bone * F. Ferrari a, A. Miotello b, L. Pavloski ‘, E. Galvanetto a, G. Moschini d, S. Galassini d, P. Passi e, S. Bogdanovie f, S. Fazini6 f, M. Jaksi6 f and V. ValkoviC ‘Z a Dipartimento di Meccanica Strutturale, Universircidegli Studi di Trento, 38050, Mesiano, Trento, Italy b Dipartimento di Fisica, Vniversitri degli Studi di Trento, 38050, Povo, Trento, Italy ’ CSM, Trento, Italy d INFN - Laboratori Nazionali di Legnaro, Padova, Italy e Dental School, University of Padua, Italy f R Bm”koviCInstitute, Zagreb, Croatia 8 IAEA Seibersdorf Laboratories, Wien, Austria
Titanium is a good material for dental and orthopaedic implants, but many authors reported that it releases ions into the surrounding tissues and into the serum. Titanium nitride has good mechanical properties and chemical inertless and may be employed as an implant coating material. In this experiment, pure titanium and SiO, coated with TiN implants were inserted in the tibia of rats. After thirty days, the bones were taken and examined by a proton microprobe. TiN-coated implants showed a lower ion release into the bone compared with pure titanium. This suggests that TiN may be a good coating for endosseous implants.
1. IntroductioIl
Titanium and titanium-based alloys are considered to be among the best materials for endosseous dental implants and orthopaedic prosthesis, because of their excellent biological and mechanical properties. Titanium is a “qioinert” metal in the sense that, when inserted into the bone, it leads to the so-called “osseointegration”, i.e. a morphological and functional bonding to the bone occurs. In other words, newly formed bone surrounds and embeds the implant, without any interposition of fibrous connective tissue, that is considered as undesirable for the long-term clinical success [l]. Some other bioninert implant materials exist, but they have some problems regarding mechanical strength and long-term resorption. For these reasons, titanium and its alloys are the most utilized materials for endosseous implants. Even though the corrosion resistance of titanium is very high, because of the passivation due to its surface oxides, it has been pointed out that titanium and its alloys leak Ti ions into the surrounding tissues and the biological fluids. Some researches, carried out in vitro, demonstrated that titanium alloys release Ti ions into saline solutions 1131,and that ion release may be greater with titanium than with cobalt-chromium alloys [2], although they * Work partially supported by the Commission of the European Communities [Contract No. CI 1-0331-I(A)]. 0168-583X/93/$06.00
are commonly considered as less biocompatible as far as osseointegration of implants is concerned. High concentrations of titanium were found in the organs, especially the lungs, of rabbits with implants [7]; a significant Ti-ion release was also found in the bone of dogs with endosseous implants [S]. Studies in the rat showed that ammonium oxalotitanate injected into the peritoneum concentrates in most tissues, especially in the spleen [6]; high concentrations of titanium were also found in many organs and the peri-implant tissues of baboons bearing prosthetic replacements of long bones [15]. As far as humans are concerned, a significant peri-implant release of titanium was found in the peri-implant tissues of patients with an orthopaedic prosthesis [ll], in the serum of subjects with loose total hipreplacements 191, and in patients with dental implants [lo]. It must be underlined that no titanium-related clinical disturbance has been reported up to now, but an in vitro study demonstrated that Ti ions can inhibit the formation of apatite in vitro, so that Ti-ions leaking may not be considered as completely safe for the clinical success of the implants. It has been reported that implants coated with titanium nitride show a lesser ion leakage in vitro, compared with Ti or Co-Cr-Mo alloy implants [14]. The aim of this work was to evaluate the ion release of commercially pure titanium and TiN-coated implants in the bone of rats.
0 1993 - Elsevier Science Publishers B.V. All rights reserved
VII. PIXE, MICROPROBES,
..
F. Ferrari et al. / Metal-ion release from Ti and TiN coated implants
422 2. Materials
and methods
Fourteen male adult Wistar-Lewis rats, each weighing about 400 g, were utilized in these experiments. In general anesthesia with ethilic ether, the tibia was surgically exposed, and an implant was inserted in its middle, after drilling the bone with a low-speed burr, under saline irrigation. Each implant was parallepipedal, measuring about 5 X 1 X 1 mm; the Ti splinter was obtained turning surgical implants, while TiN was coated over SiO, rods, by means of the PVD (physical vapour deposition) technique. The implants were stabilized in the cortical plate, and inserted until they were in contact with the opposite one. Seven rats received a titanium implant, while the other seven received a TiN-coated one. At the end of the operation, the soft tissues were sutured over the bone, carefully covering the implants. After 30 days, the animals were sacrificed by cervical luxation, the tibiae taken and fixed in neutral formalin for ten days. The soft tissues were then removed, and the bones and the implants were cut along their length, using a rotating diamond disk. They were subsequently mounted on metal grids, and examined by means of a proton microprobe.
3. Coating Titanium nitride coatings, 0.2-0.3 Frn thick, have been deposited on SiO, implants. Sputtered coatings have been prepared in a LH 2700 machine operating in a reactive mode at a base pressure of 2 X lo5 Pa. The films were prepared with the substrate biased at V, = - 100 V, the process lasting typically 120 s. The chemical composition of the films was characterized by Auger electron spectroscopy @ES) combined with Ar+ ion sputtering. The sputtered films (as we have reported in figs. 1 and 2 of ref. [3] where AES and X-ray analysis of titanium nitride films prepared at different bias conditions are illustrated) appear to be substantially homogeneous, this results from the constant behavior of the Ti + N and Ti Auger signals along the depth. X-ray analysis indicates that the films have a cubic fee structure [3] while scanning electron microscopy @EM) micrographs of the film surface show that the films were relatively flat [3].
well defined implant-bone transitions for irradiation. Self-supporting bone samples, mounted on aluminum holders, were positioned in the proton microprobe scattering chamber. The proton microprobe used is the tandem Van de Graaf accelerator of the R. BoSkovi6 Institute in Zagreb. Microbeam currents of around 50 pA yielded good detection limits for titanium in bone (as low as 50 ppm). Spatial resolution (determined to be 5 pm) was estimated by scanning across a copper mesh, 10 p,rn thick, with a cell distance of 25 pm.
5. Results and discussion
From the sample set only two have been chosen for detailed investigation, one containing a Ti implant, and the other one a TiN-coated implant. Other samples were discarded because of various irregularities like the absence of well defined crossing between implant and bone and the irregular shape or position of implant compared to bone. First, the beam was scanned over the area of inter, est to obtain Ti and Ca elemental maps covering areas of 300 X 500 Frn’. In order to find possible elements diffusion, these elemental maps were used to perform line scans over the interface between the implant and the surrounding bone. A few line scans were done for each bone in different directions. Ka X-ray intensities along the linear scans were compared for bones with Ti and TiN coated implants. Fig. 1 is showing the results of the above mentioned comparison. The intensities are normalized to the same number of counts inside the implant region (distance 0 is the border of the implant). There are visible indications that the Ti X-ray intensity is higher in the intermediate region between implant and bone in the case of Ti implantat. This can indicate a higher Ti ion diffusion for Ti implants, as
4. Microbeam Bones with implants were sectioned along their length, to obtain a smooth clean surface to irradiate. All samples were dried and the sample surfaces were investigated under a microscope in order to identify
Distance from implant border (microns)
Fig. 1. Ti KU X-ray intensities along the line scan for Ti implant and TiN coated implant. The distance is measured from the implant border, where it is equal to zero.
F. Ferrari et al. / Metal-ion release from Ti and TN coated implants
compared with TiN-coated implants. However, in order to make definite conclusions for the possible higher or lower diffusions of titanium into the bone, more measurements, regarding the secondary emission [16] at positions close to the bone-implant contact, have to be performed. This problem could be solved by removal of the implant before the analysis or preparation of thin sections. If thin sections are prepared, optically invisible undersurface irregularities which can also contribute to the slope of the X-ray intensity at the interface can be avoided. A possible diffusion difference will be better visible when bone samples with a longer time difference between implant insertion and animal sacrification will be available. Anyhow, these preliminary results suggest that TiN may be a good coating for dental implants and orthopaedic prostheses, as far as ion release into the surrounding bone is concerned. It can also be considered mechanically very reliable, because it has a high hardness, a very good load bearing capability, and a low friction coefficient [14]. It has been reported that TiN has a very good biocompatibility [12], and that TiN coated implants become os-
seointegrated in the same way as commercially pure titanium [8]. These latter findings have been confirmed by some results we got in the rat, and still unpublished, which suggest that TiN-coated endosseous implants behave much very like to pure titanium. If further research will attest its good biological features, TiN may become one of the main implant coating materials.
423
References [l] T. Albrektsson and U. Lekholm, Dent. Cl. N. Am. 33 (1989) 537. [2] N.C. Blumenthal, V.J. Cosma, Biomed. Mater. Res.: Appl. Biomater. 23 (1989) AB: 13. [3] M. Bonelli, L.A. Guzman, A. Miotello, L. Calliari. M. Elena and P.M. Ossi, Vacuum 43 (1992) 459. [4] P. Ducheyne and ICE. Healy, J. Biomed. Mater. Res. 22 (1988) 1137. [S] P. Ducheyne, G. Williams, M. Martens and J. Helsen, J. Biomed. Mater. Res. 18 (1984) 293. [6] J. Edel, E. Marafrante and B. Sabbioni, Hum. Toxicol. 4 (1985) 177. [7] A.B. Ferguson, Y. Akahoshi, P.G. Laing and E.S. Hodge, J. Bone Joint Surg. 44 (1962) 323. [8] K. Hayashi, N. Matsuguchi, K. Uenoyama, T. Kenemaru and Y. Sugioka, J. Biom. Mater. Res. 23 (1989) 1247. [9] J.J. Jacobs, AK. Skipor, J. Black, R.M. Urban and J.O. Galante, J. Bone Joint Surg. Am. 73 (1991) 1475. [lo] J.C. Keller, F.A. Young and B. Hansel, Dent. Mater. 1 (1985) 41. [ll] G. Meachim and D.F. Williams, J. Biomed. Mater. Res. 7 (1973) 555 [12] T. Suka, J. Jpn. Orthop. Ass. 60 (1986) 637. [13] A. Wisbey, P.J. Gregson, L.M. Peter and M. Tube, Biomater. 12 (1991) 470. [14] A. Wisbey, P.J. Gregson and M. Tuke, Biomater. 8 (1987) 477. [15] J.L. Woodman, J.J. Jacobs, J.O. Galante and R.M. Urban, J. Orthop. Res. 1 (1984) 421. [16] G. Demortier, S. Mathot and C. Steukers, 6th Int. PIXE Conf. Tokyo, Japan, 1992, Nucl. Instr. and Meth. B75 (1993) 347.
VII. PIXE, MICROPROBES,
...
Nuclear Instruments and Methods in Physics Research B79 (1993) 421-423 North-Holland
Beam Intemctions with Materials&Atoms
Metal-ion release. from titanium and TiN coated implants in rat bone * F. Ferrari a, A. Miotello b, L. Pavloski ‘, E. Galvanetto a, G. Moschini d, S. Galassini d, P. Passi e, S. Bogdanovie f, S. Fazini6 f, M. Jaksi6 f and V. ValkoviC ‘Z a Dipartimento di Meccanica Strutturale, Universircidegli Studi di Trento, 38050, Mesiano, Trento, Italy b Dipartimento di Fisica, Vniversitri degli Studi di Trento, 38050, Povo, Trento, Italy ’ CSM, Trento, Italy d INFN - Laboratori Nazionali di Legnaro, Padova, Italy e Dental School, University of Padua, Italy f R Bm”koviCInstitute, Zagreb, Croatia 8 IAEA Seibersdorf Laboratories, Wien, Austria
Titanium is a good material for dental and orthopaedic implants, but many authors reported that it releases ions into the surrounding tissues and into the serum. Titanium nitride has good mechanical properties and chemical inertless and may be employed as an implant coating material. In this experiment, pure titanium and SiO, coated with TiN implants were inserted in the tibia of rats. After thirty days, the bones were taken and examined by a proton microprobe. TiN-coated implants showed a lower ion release into the bone compared with pure titanium. This suggests that TiN may be a good coating for endosseous implants.
1. IntroductioIl
Titanium and titanium-based alloys are considered to be among the best materials for endosseous dental implants and orthopaedic prosthesis, because of their excellent biological and mechanical properties. Titanium is a “qioinert” metal in the sense that, when inserted into the bone, it leads to the so-called “osseointegration”, i.e. a morphological and functional bonding to the bone occurs. In other words, newly formed bone surrounds and embeds the implant, without any interposition of fibrous connective tissue, that is considered as undesirable for the long-term clinical success [l]. Some other bioninert implant materials exist, but they have some problems regarding mechanical strength and long-term resorption. For these reasons, titanium and its alloys are the most utilized materials for endosseous implants. Even though the corrosion resistance of titanium is very high, because of the passivation due to its surface oxides, it has been pointed out that titanium and its alloys leak Ti ions into the surrounding tissues and the biological fluids. Some researches, carried out in vitro, demonstrated that titanium alloys release Ti ions into saline solutions 1131,and that ion release may be greater with titanium than with cobalt-chromium alloys [2], although they * Work partially supported by the Commission of the European Communities [Contract No. CI 1-0331-I(A)]. 0168-583X/93/$06.00
are commonly considered as less biocompatible as far as osseointegration of implants is concerned. High concentrations of titanium were found in the organs, especially the lungs, of rabbits with implants [7]; a significant Ti-ion release was also found in the bone of dogs with endosseous implants [S]. Studies in the rat showed that ammonium oxalotitanate injected into the peritoneum concentrates in most tissues, especially in the spleen [6]; high concentrations of titanium were also found in many organs and the peri-implant tissues of baboons bearing prosthetic replacements of long bones [15]. As far as humans are concerned, a significant peri-implant release of titanium was found in the peri-implant tissues of patients with an orthopaedic prosthesis [ll], in the serum of subjects with loose total hipreplacements 191, and in patients with dental implants [lo]. It must be underlined that no titanium-related clinical disturbance has been reported up to now, but an in vitro study demonstrated that Ti ions can inhibit the formation of apatite in vitro, so that Ti-ions leaking may not be considered as completely safe for the clinical success of the implants. It has been reported that implants coated with titanium nitride show a lesser ion leakage in vitro, compared with Ti or Co-Cr-Mo alloy implants [14]. The aim of this work was to evaluate the ion release of commercially pure titanium and TiN-coated implants in the bone of rats.
0 1993 - Elsevier Science Publishers B.V. All rights reserved
VII. PIXE, MICROPROBES,
..
F. Ferrari et al. / Metal-ion release from Ti and TiN coated implants
422 2. Materials
and methods
Fourteen male adult Wistar-Lewis rats, each weighing about 400 g, were utilized in these experiments. In general anesthesia with ethilic ether, the tibia was surgically exposed, and an implant was inserted in its middle, after drilling the bone with a low-speed burr, under saline irrigation. Each implant was parallepipedal, measuring about 5 X 1 X 1 mm; the Ti splinter was obtained turning surgical implants, while TiN was coated over SiO, rods, by means of the PVD (physical vapour deposition) technique. The implants were stabilized in the cortical plate, and inserted until they were in contact with the opposite one. Seven rats received a titanium implant, while the other seven received a TiN-coated one. At the end of the operation, the soft tissues were sutured over the bone, carefully covering the implants. After 30 days, the animals were sacrificed by cervical luxation, the tibiae taken and fixed in neutral formalin for ten days. The soft tissues were then removed, and the bones and the implants were cut along their length, using a rotating diamond disk. They were subsequently mounted on metal grids, and examined by means of a proton microprobe.
3. Coating Titanium nitride coatings, 0.2-0.3 Frn thick, have been deposited on SiO, implants. Sputtered coatings have been prepared in a LH 2700 machine operating in a reactive mode at a base pressure of 2 X lo5 Pa. The films were prepared with the substrate biased at V, = - 100 V, the process lasting typically 120 s. The chemical composition of the films was characterized by Auger electron spectroscopy @ES) combined with Ar+ ion sputtering. The sputtered films (as we have reported in figs. 1 and 2 of ref. [3] where AES and X-ray analysis of titanium nitride films prepared at different bias conditions are illustrated) appear to be substantially homogeneous, this results from the constant behavior of the Ti + N and Ti Auger signals along the depth. X-ray analysis indicates that the films have a cubic fee structure [3] while scanning electron microscopy @EM) micrographs of the film surface show that the films were relatively flat [3].
well defined implant-bone transitions for irradiation. Self-supporting bone samples, mounted on aluminum holders, were positioned in the proton microprobe scattering chamber. The proton microprobe used is the tandem Van de Graaf accelerator of the R. BoSkovi6 Institute in Zagreb. Microbeam currents of around 50 pA yielded good detection limits for titanium in bone (as low as 50 ppm). Spatial resolution (determined to be 5 pm) was estimated by scanning across a copper mesh, 10 p,rn thick, with a cell distance of 25 pm.
5. Results and discussion
From the sample set only two have been chosen for detailed investigation, one containing a Ti implant, and the other one a TiN-coated implant. Other samples were discarded because of various irregularities like the absence of well defined crossing between implant and bone and the irregular shape or position of implant compared to bone. First, the beam was scanned over the area of inter, est to obtain Ti and Ca elemental maps covering areas of 300 X 500 Frn’. In order to find possible elements diffusion, these elemental maps were used to perform line scans over the interface between the implant and the surrounding bone. A few line scans were done for each bone in different directions. Ka X-ray intensities along the linear scans were compared for bones with Ti and TiN coated implants. Fig. 1 is showing the results of the above mentioned comparison. The intensities are normalized to the same number of counts inside the implant region (distance 0 is the border of the implant). There are visible indications that the Ti X-ray intensity is higher in the intermediate region between implant and bone in the case of Ti implantat. This can indicate a higher Ti ion diffusion for Ti implants, as
4. Microbeam Bones with implants were sectioned along their length, to obtain a smooth clean surface to irradiate. All samples were dried and the sample surfaces were investigated under a microscope in order to identify
Distance from implant border (microns)
Fig. 1. Ti KU X-ray intensities along the line scan for Ti implant and TiN coated implant. The distance is measured from the implant border, where it is equal to zero.
F. Ferrari et al. / Metal-ion release from Ti and TN coated implants
compared with TiN-coated implants. However, in order to make definite conclusions for the possible higher or lower diffusions of titanium into the bone, more measurements, regarding the secondary emission [16] at positions close to the bone-implant contact, have to be performed. This problem could be solved by removal of the implant before the analysis or preparation of thin sections. If thin sections are prepared, optically invisible undersurface irregularities which can also contribute to the slope of the X-ray intensity at the interface can be avoided. A possible diffusion difference will be better visible when bone samples with a longer time difference between implant insertion and animal sacrification will be available. Anyhow, these preliminary results suggest that TiN may be a good coating for dental implants and orthopaedic prostheses, as far as ion release into the surrounding bone is concerned. It can also be considered mechanically very reliable, because it has a high hardness, a very good load bearing capability, and a low friction coefficient [14]. It has been reported that TiN has a very good biocompatibility [12], and that TiN coated implants become os-
seointegrated in the same way as commercially pure titanium [8]. These latter findings have been confirmed by some results we got in the rat, and still unpublished, which suggest that TiN-coated endosseous implants behave much very like to pure titanium. If further research will attest its good biological features, TiN may become one of the main implant coating materials.
423
References [l] T. Albrektsson and U. Lekholm, Dent. Cl. N. Am. 33 (1989) 537. [2] N.C. Blumenthal, V.J. Cosma, Biomed. Mater. Res.: Appl. Biomater. 23 (1989) AB: 13. [3] M. Bonelli, L.A. Guzman, A. Miotello, L. Calliari. M. Elena and P.M. Ossi, Vacuum 43 (1992) 459. [4] P. Ducheyne and ICE. Healy, J. Biomed. Mater. Res. 22 (1988) 1137. [S] P. Ducheyne, G. Williams, M. Martens and J. Helsen, J. Biomed. Mater. Res. 18 (1984) 293. [6] J. Edel, E. Marafrante and B. Sabbioni, Hum. Toxicol. 4 (1985) 177. [7] A.B. Ferguson, Y. Akahoshi, P.G. Laing and E.S. Hodge, J. Bone Joint Surg. 44 (1962) 323. [8] K. Hayashi, N. Matsuguchi, K. Uenoyama, T. Kenemaru and Y. Sugioka, J. Biom. Mater. Res. 23 (1989) 1247. [9] J.J. Jacobs, AK. Skipor, J. Black, R.M. Urban and J.O. Galante, J. Bone Joint Surg. Am. 73 (1991) 1475. [lo] J.C. Keller, F.A. Young and B. Hansel, Dent. Mater. 1 (1985) 41. [ll] G. Meachim and D.F. Williams, J. Biomed. Mater. Res. 7 (1973) 555 [12] T. Suka, J. Jpn. Orthop. Ass. 60 (1986) 637. [13] A. Wisbey, P.J. Gregson, L.M. Peter and M. Tube, Biomater. 12 (1991) 470. [14] A. Wisbey, P.J. Gregson and M. Tuke, Biomater. 8 (1987) 477. [15] J.L. Woodman, J.J. Jacobs, J.O. Galante and R.M. Urban, J. Orthop. Res. 1 (1984) 421. [16] G. Demortier, S. Mathot and C. Steukers, 6th Int. PIXE Conf. Tokyo, Japan, 1992, Nucl. Instr. and Meth. B75 (1993) 347.
VII. PIXE, MICROPROBES,
...