Comparison of chemically and pharmaceutically modified titanium and zirconia implant surfaces in dentistry: a study in sheep

YIJOM-1445; No of Pages 8 Int. J. Oral Maxillofac. Surg. 2008; xxx: xxx–xxxdoi:available online at http://www.sciencedirect.com Comparison of chemically and J. D. K. Voelter, D. M. Schnabelrauch, F. T. Hefti, K. K. B. von Rechenberg1Musculoskeletal Research Unit, Equine titanium and zirconia implant Hospital, Vetsuisse Faculty ZH, University ofZurich, Winterthurerstr. 260, CH-8057 Zurich,Switzerland; 2Max Bergmann Center forBiomaterials, Institute of Materials Science, surfaces in dentistry: a study in DresdenUniversityofTechnology, Budapester Str. 27, 01069 Dresden,Germany; 3Biomaterials Department, INNOVENT e. V., Pruessingstrasse 27B, D-07745 Jena, Germany; 4Thommen Medical,Hauptstrasse 26d, CH 4437 Waldenburg,Switzerland; 5Veterinary Anesthesiology,Equine Hospital, Vetsuisse Faculty ZH,University of Zurich, Winterthurerstr. 260, CH- J. D. Langhoff, K. Voelter, D. Scharnweber, M. Schnabelrauch, F. Schlottig, T. Hefti, 8057 Zurich, Switzerland K. Kalchofner, K. Nuss, B. von Rechenberg: Comparison of chemically andpharmaceutically modified titanium and zirconia implant surfaces in dentistry: a studyin sheep. Int. J. Oral Maxillofac. Surg. 2008; xxx: xxx–xxx. # 2008 InternationalAssociation of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rightsreserved.
Abstract. Advanced surface modifications and materials were tested on the sameimplant geometry. Six types of dental implants were tested for osseointegrationafter 2, 4 and 8 weeks in a sheep pelvis model. Four titanium implant types weretreated with newly developed surface modifications, of which two were chemicallyand two were pharmacologically modified. One implant was made of zirconia. Asandblasted and acid-etched titanium surface was used as reference. The chemicallymodified implants were plasma-anodized or coated with calcium phosphate. Thepharmacological coatings contained either bisphosphonate or collagen type I with con superficie "Zerafil" de ZERAMEX-T chondroitin sulphate. The implants were evaluated using macroscopic, radiographicand histomorphometric methods.
All implants were well osseointegrated at the time of death. All titanium implants had similar bone implant contact (BIC) at 2 weeks (57–61%); only zirconia wasbetter (77%). The main BIC increase was between 2 and 4 weeks. The Keywords: dental implants; zirconia; titanium; pharmacologically coated implants (78–79%) and the calcium phosphate coating surface modification; histomorphometry; (83%) showed similar results compared with the reference implant (80%) at 8 weeks. There were no significant differences in BIC. Compared with previousstudies the results of all implants were comparatively good.
Accepted for publication 3 September 2008 Over the last decades, titanium or its alloys patibilityThese properties ensure good gery, while allowing efficient osseointe- has become a gold standard as a base for anchorage within the mandible or maxil- gration. Apart from good implant design tooth reconstruction in dental implantol- lary bone. The aim is to achieve shorter ogy, because of its mechanical strength, healing periods for implants, in order to * The first two authors contributed equally chemical stability and excellent biocom- load them as soon as possible after sur- to this work.
# 2008 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Langhoff JD, et al., Comparison of chemically and pharmaceutically modified titanium and zirconiaimplant surfaces in dentistry: a study in sheep, Int J Oral Maxillofac Surg (2008), YIJOM-1445; No of Pages 8 Langhoff et al.
related to mechanical anchorage, these degeneration associated with implants requirements may be met by modifying often uncover parts of the metal implant The calcium phosphate surface was coated the implant surface, bearing in mind that showing a bluish discoloration of the over- using electrochemical assistance in an the most important surface properties for lying gingiva. The use of zirconia implants aqueous solution containing calcium and (metallic) implants are topography, chem- avoids this complication and accedes to phosphate ions. The coating consists of the istry, surface charge and the request of many patients for metal-free two calcium phosphate phases, hydroxya- To improve surface properties two implants. The material also provides high patite and brushite, and is commercially main approaches were used either opti- strength, fracture toughness and biocom- available. The anodic plasma chemical mizing the micro-roughness (e.g. sand- patibility. Osseointegration is approxi- blasting and acid-etching) or applying mately the same as with advanced anodization method, which bioactive coatings (e.g. calcium phos- The authors hypothesize that chemical allows anodic oxide layer formation and phate, bisphosphonate, collagen). Opti- and pharmacological surface modifica- mizing the micro-roughness results in tions to titanium initiate a stronger bone phases in a single process step. The enlarged surfaces providing improved response than an advanced sandblasted method exploits the dielectric breakdown conditions for osteogenic cell attachment and acid-etched surface alone. They tested of anodic oxide films to produce a porous and proliferation. In recent studies, histo- whether a surface-treated zirconia can oxide layer that contains significant mophometric and biomechanical compar- compete with sophisticated titanium sur- amounts of electrolyte components. The isons of such optimized implant surfaces faces. The bone response to the implant electrolyte contained calcium and phos- to machined implants showed better modifications was tested on the identical phate ions, leading to a porous surface values for short time osseointegration.
established implant geometry using histo- containing calcium phosphate.
These surfaces were also optimized for The collagen coating was based on an their wettability for potentially enhanced extracellular matrix containing chondroi- implant–tissue interaction and better tin sulphate, prepared by fibrillogenesis of osseointegration, achieved by rinsing Material and methods the collagen in the presence of CS, and under an N2 atmosphere and submersion performed as dip coating in a collagen/ in an isotonic NaCl solution following chondroitin sulphate solution. The bispho- acid-etching. The new generation of thin Overall, 6 types of implants with identical sphonate coated implants were immobi- calcium phosphate based coatings pro- implant geometry were tested lized with an alendronate solution, to a vide high wettability and were described All titanium and zirconia implants were final concentration of 10 mg/cm2.
as highly potential sandblasted and partially etched prior to The zirconia implants were manufac- Another approach is to add bioactive the surface treatments, similar to the refer- tured from yttrium partially stabilized zir- components to titanium surfaces. One ence. The surfaces of the chemically mod- method uses extracellular matrix ligands, ified implants were either plasma anodized implants were sandblasted and etched in the RGD-peptide sequence, for better or coated with calcium phosphate. The an alkaline bath.
osteoblast attachment and enhanced bone remodellingSCHULER et al.used a were either coated with bisphosphonate functionalized coating (poly(L-lysine)- or collagen type I. An acid-etched and graft-poly(ethylene glycol)) to present Animal model and study design sandblasted implant made of titanium bioligands for interaction with osteoblasts (grade 4, SPI1ELEMENT, Thommen A total of 15 sheep underwent surgery. All in vitro. Faster colonization of the implant Medical AG, Waldenburg, Switzerland) sheep were full-grown, aged 2–3 years, surface by osteoblasts also inhibits bacter- served as the reference and control for not gestating females and 49–87 kg (aver- the surface modifications.
age 68 kg). General guidelines for care A new method uses nucleic acid, single strands, fixed electrochemically via theirtermini by anodically growing an oxide Table 1. Implant groups, their abbreviations and sample size.
layer on Ti6Al7Nb as anchor structures to load surfaces with bioactive molecules Sandblasted and acid etched linked to complementary The bioactivity of surfaces can be enhanced using drug eluting coatings, Calcium Phosphate which are supposed to influence bone healing, for example by activating osteo- blasts, suppressing osteoclasts or stimulat- ing the production and distribution of growth factors such as BMP-2.
Collagen I + Chondroitin Sulfate An increase in the mechanical fixation of implants has been achieved with local delivery of Other stu- dies showed the high potential of growth Zirconia has gained attention as an implant material because of its white col- our, which makes it aesthetically attrac- Apical bone loss and gingival * SPI ELEMENT, Thommen Medical.
Please cite this article in press as: Langhoff JD, et al., Comparison of chemically and pharmaceutically modified titanium and zirconiaimplant surfaces in dentistry: a study in sheep, Int J Oral Maxillofac Surg (2008), doi:

YIJOM-1445; No of Pages 8 Comparison of chemically and pharmaceutically modified titanium and zirconia implant surfaces in dentistry for the wound before the animal wasturned over to the other side. The contral-ateral pelvis was operated on in an iden-tical manner.
Postoperative treatment consisted of an antiphlogistic and analgesic, as well asantibiotic medication for 4 days (bupre-norphin 0.01 mg/kg i.m. t.i.d. during thefirst 24 h, benzylpenicillin (30000 I.U./kgi.v. b.i.d.), gentamycin (4 mg/kg i.v. s.i.d.)and carprofen (4 mg/kg i.v. s.i.d.).
Fluorochrome labelling Fig. 1. Implant locations in the iliac bone of a sheep in a dorso-ventral view.
Bone healing and remodelling was fol- and use of animals in research have been nously thre times a day. In addition, they lowed by labelling new bone apposition received 500 Units of equine tetanus with fluorochrome at defined points approved by the local veterinary authori- serum as a single subcutaneous applica- of time. The first labelling with calcein ties (approval no.159/2005). The sheep tion (Tetanus Serum Veterinaria AG, Zur- green (10 mg/kg s.c.) was performed 2 were kept in groups containing a maxi- ich, Switzerland).
weeks after implantation. In the 8 week- mum of 4 animals. Their general condition The animals were placed in lateral group, a second label was injected at 6 was checked three times a day to accom- recumbency and access to the pelvis weeks using xylenol orange (90 mg/kg plish pain monitoring, to detect variations was achieved using a standard operation in wellbeing and injuries of the musculos- procedure. A 20 cm long cut was made in the skin in the longitudinal direction of the Preparation and evaluation of bone n = 110) were placed in the iliac bones iliac bone at the mid-pelvis line. The of the pelvis. Bone structure was predo- fascia was cut and the middle gluteal minantly of cancellous quality in the cra- muscle and tensor fasciae latae were sepa- The bones were harvested after killing the nial part with increasing cortical thickness rated by blunt dissection. In the distal half animals. They were freed of all soft tissue, (up to 3 mm) toward the caudal part. An of the iliac bone the tendinous insertion of revealing the implants in the iliac bone.
implantation scheme was worked out to the deep and middle gluteal muscles was The firm seat of the implants within the distribute all implant types homogenously severed from the iliac crest with a scalpel bone was tested qualitatively by manual to 7 implantation sites per iliac bone and the muscles were bluntly removed pressure and the caps were removed.
(The study design aimed to from the iliac bone shaft. A Finocchietto Thereafter, the intact pelvis bone was achieve the statistical minimum of 6 sam- retractor was used to expose the entire radiographed using a faxitron machine ples per implant group (one implant type iliac wing. Holes were drilled using the (Cabinet X-ray-faxitron series, model was not evaluated for the present study) 43855A, Hewlett Packard1, USA) for for each healing period of 2, 4 and 8 Medical AG, Waldenburg, Switzerland) documentation of implant placement and weeks, with 5 animals per time point.
with a 2.0 mm pilot drill, widened with verification of proper seat. Then the bone Additional implants were placed for a a 2.8 mm and finally with a 3.5 mm drill.
was cut into 1.5  1.5 cm cubes with a concurrent biomechanical analysis (the A drill sleeve was used to ensure the band saw (K 410, Kolbe GmbH, Elchin- topic of a separate study). Animals were designated drill depth according to the gen, Germany), containing one implant.
killed in the University's slaughterhouse implant design and the depth was con- Samples were fixed in 40% alcoholic solu- according to ethical standards.
firmed with a depth gauge (Thommen tion for 14 days and were routinely pro- Medical AG, Waldenburg, Switzerland).
The self-tapping implants (SPI1ELE- histology. They were submitted to a MENT, Thommen Medical AG, Walden- dehydration process in an ascending series After sedation with medetomidine (5 mg/ burg, Switzerland) were placed according of ethanol solutions (50, 70, 96, 100%), kg, DomitorTM, Orion Pharma Animal to the implantation scheme and using the Health, Finland) anaesthesia was induced specific instruments supplied with the vacuum. Samples were infiltrated in using ketamine (2 mg/kg, Narketan1 10, implant system. Healing caps were placed pMMA solution (poly methacrylic acid- Chassot GmbH, Germany) in combination to prevent tissue ingrowth in the abutment methylester; dibuthylphtalate and perka- with diazepam (0.01 mg/kg, Valium1, connection area of the implant head.
dox in a proportion 89.5: 10: 0.5) for 7 Roche, Switzerland). After intubation Implant setting was documented with digi- days, embedded and polymerized in anaesthesia was maintained with 0.8 tal photographs. The muscles were reposi- Teflon containers. Samples were posi- Vol% isoflurane (Forene1, Abbot AG, tioned to assure that implants were cut Switzerland) in O2 and an infusion of resutured to its origin using a cross pattern parallel to the longitudinal axis. Two Ringer's solution with 60 mg/l ketamine of single (at the edges) and continuous ground sections were cut at the maximum (NarketanTM 10, Chassot GmbH, Ger- sutures. Fascia and subcutis were closed diameter of the implant using a low speed many) at a rate of 10 ml/kg/h. As a pro- with the same synthetic resorbable suture diamond saw (Leica1 SP 1600, Leica1 phylaxis against infection all animals (Polyglactin; Vicryl1 2-0, Johnson&- Instruments GmbH, Nussloch, Germany).
received 30,000 IU/kg penicillin (Hoechst Johnson Intl.) while the skin was closed One section of 200 mm was used for nor- AG, Germany) and 6 mg/kg gentamicin mal bone histology, applying a surface (Streuli & Co AG, Switzerland) intrave- ULC1). Gauze was applied as protection staining with toluidine blue. The thinner, Please cite this article in press as: Langhoff JD, et al., Comparison of chemically and pharmaceutically modified titanium and zirconiaimplant surfaces in dentistry: a study in sheep, Int J Oral Maxillofac Surg (2008),

YIJOM-1445; No of Pages 8 Langhoff et al.
ing implantation it was noticed, that thezirconia implants required slightly moreforce for insertion compared with the tita-nium implants.
Macroscopic and radiological evaluation After preparation of the muscle above theimplants, the tissue layer directly at thebone–implant surface was gel- and fat-likeafter 2 weeks. A soft tissue layer hadformed after 4 weeks, which developedinto a periosteum-like layer with callusformation later. At 2 and 4 weeks, hae-matoma were rarely visible around theimplants. Overall, no signs of inflamma-tion or infection could be found, indicated Fig. 2. Illustration of the thread wise evaluation of the bone implant contact (BIC). Estimation through swelling, reddening or other of the percentage was supported with a 10% step grid.
degradation of surrounding tissue. Allimplants were firmly seated.
Radiographs demonstrated all implants native section (150 mm) was used for tify significant differences, mean values to be still in place. No fractures or zones of fluorescence microscopy (Leica, DMR, and standard deviations using a specific bone resorption could be found.
UV light source and Filter I3 for calcein soft ware (SPSS 13.0 for Macintosh). Sig- green and xylenol orange, Glattbrugg, nificance level was set at p < 0.05.
Switzerland). Before the 200 mm sectionswere glued to the opal, acrylic Plexiglas Radiographs of the thick sections con- slides (Wachendorf, Perspex GS, Acrylic- firmed the macroradiographic results of glas Opal 1013) microradiographs, using a absence of bone resorption. Radiodense Surgery and postoperative period high-resolution analogue film (Kodak structures were visible in detail and could Oncology Film, Eastman Kodak Com- All surgery was uneventful and the ani- be clearly identified as bone ( pany, Rochester, NY), were taken to mals recovered from anaesthesia quickly.
Radiodense structures and bone tissue visualize the stage of calcification of the The sheep were able to walk immediately stained with toluidine blue matched bone samples adjacent to the metallic after recovery, but showed signs of mild exactly. Except for a small seam of osteoid muscle soreness for 1–2 days after sur- all of the new bone formation was calci- gery. Thereafter, no signs of lameness or fied at all time points. The microradio- other discomfort were seen. Insertion of graphs were not evaluated additionally all implants proceeded smoothly, but dur- besides the stained histologies.
Using the toluidine-stained thick sections,a semi-quantitative evaluation of the boneimplant contact (BIC) was made. For this,the percentage of direct contact betweenmineralized bone and the titanium surfacewas determined by intersection countingwithin the thread area. Six thread pitcheswere counted per sample. The evaluationwas performed at calibrated digital pic-tures at 10x magnification (Leica macro-scope M420, Leica DFC320, 3088x2550pixels, Leica Microsystems, Germany).
Two pictures covered the full threadedpart in high resolution. The percentageof BIC was estimated in steps of 10%Means of thread counts perimplant were calculated.
Statistical analysis In a first step, factors as individual differ-ence and position of the implant could beexcluded as not significant. In a second Fig. 3. Calcification of new bone formation (arrows) at the implant was proved by matching step, comparison of implant types at each areas of radiodense (microradiograph, on the left) and stained structures (toluidine blue dye, on point of time was performed. The analysis the right) in histological thick sections. Overview picture (5.8) of a bisphosphonate-coated of variance (ANOVA) was used to iden- titanium implant at 4 weeks.
Please cite this article in press as: Langhoff JD, et al., Comparison of chemically and pharmaceutically modified titanium and zirconiaimplant surfaces in dentistry: a study in sheep, Int J Oral Maxillofac Surg (2008), doi: YIJOM-1445; No of Pages 8 Comparison of chemically and pharmaceutically modified titanium and zirconia implant surfaces in dentistry Fig. 4. A matrix of representative histological pictures of all implant types and time points (2, 4 and 8 weeks) at 10 magnification. Surface wereeither sandblasted and acid etched (Ref), anodic plasma treated (APC), calcium phosphate (CaP), bisphosphonate (BisP), collagen withchondroitin sulfate (Coll+) coated or of zirconia (Zr).
Evaluation of histology samples Remodeling in the cortical bone started types and time points. All titanium types by 4 weeks in some samples and was were nearly similar at 2 weeks (59–62% All sections were cut precisely in the prominent at all implant sites at 8 weeks.
BIC) and increased with time (78–83%), middle axis, capturing the entire implant, There were no signs of pathological bone except the plasma anodized surface (58%).
enabling standardized evaluation.
resorption indicative of excessive mechan- The two chemical surface modifications ical instability or issues of bioincompat- performed very differently. The calcium revealed that implants were generally ibility (accumulation of inflammatory phosphate surface showed similar values, well seated within the bone. New bone cells) in any implant. Striking differences with the main increase at 2–4 weeks, like formation, visible as dark-bluish stain, between the implant types were not the reference, and a slight increase was present around all implants in the observed in the qualitative evaluation.
towards week 8. In contrast, the plasma cancellous bone by 2 weeks and built anodized surface lost 2% bone contact up steadily until 8 weeks (Bony initially and did not improve after 4 weeks.
debris was found in the remaining cavity Evaluation of BIC Pharmacologically modified surfaces of the implant tip, where new bone was Results of the BIC measurements performed close to the reference. The found by 2 weeks.
demonstrated clear trends between surface Please cite this article in press as: Langhoff JD, et al., Comparison of chemically and pharmaceutically modified titanium and zirconiaimplant surfaces in dentistry: a study in sheep, Int J Oral Maxillofac Surg (2008),

YIJOM-1445; No of Pages 8 Langhoff et al.
Fig. 5. Results of the bone-implant contact (BIC) measurements are given according to the three groups of implant types: Chemical (a) andpharmacological (b) titanium surface modifications and a zirconia implant (c) were evaluated for bone response and referenced by a sandblastedand acid etched implant (SPI1ELEMENT). Significant differences were not found between the groups of 6 samples per implant and time point.
collagen with chondroitin sulphate surface to show better BIC values at 8 weeks be established as a standard with a zero showed slightly higher values than the compared to the anodic plasma treated failure rate of operation and implantation.
reference implant at 2 weeks and contin- surface or zirconia implants.
Standard dental equipment (SPI1 -Sys- ued nearly equally, whereas the bispho- Finding an appropriate animal model tem, Thommen Medical) could be used sphonate coated surface was higher at 2 for testing dental implants is difficult, without limitations for predrilling and and 4 weeks.
mainly because the morphology of teeth implant placement. In this manner, clin- The zirconia implant presented 20% in animals is different from that of ical standard procedures and precision more bone contact than the titanium humans. Pigs and dogs are commonly could be applied. Also sample preparation implants at 2 weeks, improved toward 4 used as experimental animals, if dental for histology did not involve complica- weeks, then reduced at 8 weeks to below implants are applied . Apart tions or loss of samples. The sample pre- the level of the reference surface.
from different root systems and the form paration proved to be a very effective and The overall performance of the new of the incisor and molar teeth, mouth reliable method for longitudinal sections.
surfaces, except the plasma anodized, hygiene is a problem in those animals All sections were cut in the centre of the was better than the reference. Statistically after setting dental implants and, thus, implants with very little variation, so his- significant differences for BIC were not healing without infection may pose a pro- tological evaluation of osseointegration could be well standardized. The present Osseointegration is often tested in other study was mainly focused on the morpho- locations, such as the femoral condyle.
logical aspects of osseointegration, as the Evaluation of fluorochrome labeling Even though the risk of infection may be histological picture did not show any At 4 weeks, calcein green fluorescent dye excluded, the cancellous bone of the abnormalities on the cellular level. As a was exclusively visible in the new bone femoral condyle is more compact and common tool in dental research, BIC was directly at the implant, while in the 8 week stronger compared to the mandible. The regarded as an appropriate method to mea- sections xylenol orange was found directly authors' group has developed an animal sure the performance of an implant. The at the implant surface. In those specimens model in the iliac shaft of sheep, where the estimation of bone contact in 10% steps calcein green was found at a greater dis- structure of the bone is similar to that of per screw thread was regarded as ade- tance from the implant surface. Differ- the human mandible, as described by the quate. Calculation of means for each Lekholm and Zarb . Sheep is a implant was close to the accuracy of a fluorochrome dyes could not be found well-established animal for orthopedic between the implant types and, therefore, research, because of the similar remodel- threaded part of the implant was evalu- further histomorphometrical evaluations ing rate, bone structure and bone propor- were not performed.
tions as humans. The pelvis model allows Although good standardization of sur- the implantation of a relatively high num- gery and sample preparation procedures ber of implants in one sheep; by operating could be achieved, differences between on both sides intra- and inter-individual groups did not reach statistical signifi- In this study the osseointegration of mar- comparisons can be made. The animal cance. The two main reasons for this were ket standard dental implants (titanium model serves well from an ethical stand- the relatively small sample size and the grade 4, sandblasted, acid etched) was point considering animal welfare and pro- good material properties of all the tested compared with surface-treated implants tection, because surgery does not interfere implants. The minimal sample size for that were either chemically (plasma ano- significantly with normal ambulation of statistical evaluation was chosen consider- dized, calcium phosphate coated) or phar- the sheep, housing can be easily provided ing animal welfare issues and ethical con- macologically modified (bisphosphonate, appropriate to the species and handling cerns related to the use of animals in collagen type 1 containing chondroitin does not cause excessive stress.
experimental research. Since the sand- sulphate) or to zirconia implants. An The study design achieved the statistical blasted and acid-etched implants (Thom- experimental sheep pelvis model was minimum within the limitations of a jus- men Medical SPI1-System) used as a used, where all implants showed good tifiable use of animals. The implantation reference show good performance owing scheme reduced the influences of the indi- to their original titanium dif- Although statistically not significant, there vidual and the implantation site using a ferences to the modified implants were was a clear tendency for the chemically rotation system of sample distribution.
expected to be relatively small. Tenden- and pharmacologically modified implants The iliac bone as implantation site could cies for improved osseointegration follow- Please cite this article in press as: Langhoff JD, et al., Comparison of chemically and pharmaceutically modified titanium and zirconiaimplant surfaces in dentistry: a study in sheep, Int J Oral Maxillofac Surg (2008), doi: YIJOM-1445; No of Pages 8 Comparison of chemically and pharmaceutically modified titanium and zirconia implant surfaces in dentistry ing implant modification were clearly or pharmacologically treated implants and for appropriate biomedical use. BMC shown and allow further research and the reference titanium implants. Whether Musculoskelet Disord 2007: 8: 72.
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Collagen containing chondroitin sul- 8. Jones AA, Buser D, Schenk R, Woz- phate surfaces increased cell proliferation Acknowledgements. Implants were pro- J, Cochran DL. The effect of and activated osteoblasts in cell cultures as vided by Thommen Medical AG, Walden- rhBMP-2 around endosseous implants demonstrated through higher values of burg, Switzerland. The excellent work by with and without membranes in the bone markers (osteopontin, alkaline phos- S. Bierbaum (Biomaterials Department, canine model. J Periodontol 2006: 77: phatase) and larger cell sizeAdhesion INNOVENT e. V) for providing the col- molecules such as vinculin, actin and lagen containing chondroitin sulfate coat- 9. Kohal RJ, Weng D, Bachle M, Strub JR. Loaded custom-made zirconia and integrins were up-regulated in vitro. Inhi- titanium implants show similar osseoin- bition of osteoclasts does not occur in Mathys Foundation, Bischmattstrasse 12, tegration: an animal experiment. J Period- parallel. Recruitment and activation of 2544 Bettlach, Switzerland) for providing ontol 2004: 75: 1262–1268.
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zer B. Surface modification of titanium- osseointegration was assessed using the Bone and soft tissue integration to tita- based alloys with bioactive molecules histology of non-decalcified bone samples nium implants with different surface using electrochemically fixed nucleic topography: an experimental study in containing the implants alone. Although it acids. J Biomed Mater Res B Appl Bio- the dog. Int J Oral Maxillofac Implants would be interesting to understand the mater 2007: 80: 146–155.
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