Multifunctional calcium phosphate based coatings on titanium implants with integrated trace elements.

For decades, the main focus of titanium implants developed to restore bone functionality was on improved osseointegration. Additional antimicrobial properties have now become desirable, due to the risk that rising antibiotic resistance poses for implant-associated infections. To this end, the trace elements of copper and zinc were integrated into calcium phosphate based coatings by electrochemically assisted deposition. In addition to their antimicrobial activity, zinc is reported to attract bone progenitor cells through chemotaxis and thus increase osteogenic differentiation, and copper to stimulate angiogenesis. Quantities of up to 68.9 ± 0.1 µg cm- 2 of copper and 56.6 ± 0.4 µg cm- 2 of zinc were deposited; co-deposition of both ions did not influence the amount of zinc but slightly increased the amount of copper in the coatings. The release of deposited copper and zinc species was negligible in serum-free simulated body fluid. In protein-containing solutions, a burst release of up to 10 µg ml-1 was observed for copper, while zinc was released continuously for up to 14 days. The presence of zinc was beneficial for adhesion and growth of human mesenchymal stromal cells in a concentration-dependent manner, but cytotoxic effects were already visible for coatings with an intermediate copper content. However, co-deposited zinc could somewhat alleviate the adverse effects of copper. Antimicrobial tests with E. coli revealed a decrease in adherent bacteria on brushite without copper or zinc of 60%, but if the coating contained both ions there was almost no bacterial adhesion after 12 h. Coatings with high zinc content and intermediate copper content had the overall best multifunctional properties.

In vivo effect of immobilisation of bone morphogenic protein 2 on titanium implants through nano-anchored oligonucleotides.

The aim of the present study was to test the hypothesis that immobilisation of bone morphogenic proteins on the surface of titanium implants through nano-anchored oligonucleotides can enhance peri-implant bone formation. Non-coding 60-mer DNA oligonucleotides (ODN) were anchored to the surface of custom made sandblasted acid etched (SAE) titanium screw implants through anodic polarisation, gamma-sterilised with a standard dose of 25 kGy, and were hybridised with complementary 30-mer strands of DNA oligonucleotides conjugated to rhBMP2. Blank SAE implants, SAE implants with nano-anchored ODN and SAE implants with nano-anchored ODN and non-conjugated rhBMP2 served as controls. The implants were inserted into the tibiae of 36 Sprague Dawley rats. Perforations at the head and the tip of the implants allowed for bone ingrowth. Bone ingrowth into perforations and bone implant contact (BIC) as well as bone density (BD) at a distance of 200 µm from the implant surface were assessed after 1 , 4 and 13 weeks. Implants with nano-anchored ODN strands hybridised with conjugated rhBMP2 exhibited enhanced bone ingrowth into the perforations and increased BIC after 1 week as well as increased BIC after 4 weeks compared to controls. No difference was seen after 13 weeks. Bone density around the outer implant surface did not differ significantly at any of the intervals. It is concluded that rhBMP2 immobilised on the surface of titanium implants through nano-anchored oligonucleotide strands can enhance bone implant contact. The conditions of sterilisation tested allowed for handling under clinically relevant conditions.

ECM inspired coating of embroidered 3D scaffolds enhances calvaria bone regeneration.

Resorbable polymeric implants and surface coatings are an emerging technology to treat bone defects and increase bone formation. This approach is of special interest in anatomical regions like the calvaria since adults lose the capacity to heal large calvarial defects. The present study assesses the potential of extracellular matrix inspired, embroidered polycaprolactone-co-lactide (PCL) scaffolds for the treatment of 13 mm full thickness calvarial bone defects in rabbits. Moreover the influence of a collagen/chondroitin sulfate (coll I/cs) coating of PCL scaffolds was evaluated. Defect areas filled with autologous bone and empty defects served as reference. The healing process was monitored over 6 months by combining a novel ultrasonographic method, radiographic imaging, biomechanical testing, and histology. The PCL coll I/cs treated group reached 68% new bone volume compared to the autologous group (100%) and the biomechanical stability of the defect area was similar to that of the gold standard. Histological investigations revealed a significantly more homogenous bone distribution over the whole defect area in the PCL coll I/cs group compared to the noncoated group. The bioactive, coll I/cs coated, highly porous, 3-dimensional PCL scaffold acted as a guide rail for new skull bone formation along and into the implant.

Artificial extracellular matrices of collagen and sulphated hyaluronan enhance the differentiation of human mesenchymal stem cells in the presence of dexamethasone.

In this study we investigated the potential of artificial extracellular matrix (aECM) coatings containing collagen II and two types of glycosaminoglycan (GAGs) with different degrees of sulphation to promote human bone formation in biomedical applications. To this end their impact on growth and osteogenic differentiation of human mesenchymal stem cells (hMSCs) was assessed. The cell proliferation was found to be significantly retarded in the first 14 days of culture on surfaces coated with collagen II and GAGs (coll-II/GAG) as compared to tissue culture polystyrol (TCPS) and those coated with collagen II. At later time points it only tended to be retarded on coll-II/sHya3.1. Heat-inactivation of the serum significantly reduced cell numbers on collagen II and coll-II/sHya3.1. Alkaline phosphatase (ALP) activity and calcium deposition, on the other hand, were higher for coatings containing sHya3.1 and were not significantly changed by heat-inactivation of the serum. Expression levels of the bone matrix proteins bone sialoprotein (BSP-II) and osteopontin (OP) were also increased on aECM coatings as compared to TCPS, which further validated the differentiation of hMSCs towards the osteogenic lineage. These observations reveal that aECM coatings, in particular those containing sHya3.1, are suitable to promote the osteogenic differentiation of hMSCs.

Chondroitin sulfate and sulfated hyaluronan-containing collagen coatings of titanium implants influence peri-implant bone formation in a minipig model.

An improved osseous integration of dental implants in patients with lower bone quality is of particular interest. The aim of this study was to evaluate the effect of artificial extracellular matrix implant coatings on early bone formation. The coatings contained collagen (coll) in conjunction with either chondroitin sulfate (CS) or sulfated hyaluronan (sHya). Thirty-six screw-type, grit-blasted, and acid-etched titanium implants were inserted in the mandible of 6 minipigs. Three surface states were tested: (1) uncoated control (2) coll/CS (3) coll/sHya. After healing periods of 4 and 8 weeks, bone implant contact (BIC), bone volume density (BVD) as well as osteoid related parameters were measured. After 4 weeks, control implants showed a BIC of 44% which was comparable to coll/CS coated implants (48%) and significantly higher compared to coll/sHya coatings (37%, p = 0.012). This difference leveled out after 8 weeks. No significant differences could be detected for BVD values after 4 weeks and all surfaces showed reduced BVD values after 8 weeks. However, at that time, BVD around both, coll/CS (30%, p = 0.029), and coll/sHya (32%, p = 0.015), coatings was significantly higher compared to controls (22%). The osteoid implant contact (OIC) showed no significant differences after 4 weeks. After 8 weeks OIC for controls was comparable to coll/CS, the latter being significantly higher compared to coll/sHya (0.9% vs. 0.4%, p = 0.012). There were no significant differences in osteoid volume density. In summary, implant surface coatings by the chosen organic components of the extracellular matrix showed a certain potential to influence osseointegration in vivo.

Sulfated glycosaminoglycans as promising artificial extracellular matrix components to improve the regeneration of tissues.

Glycosaminoglycans (GAG) such as hyaluronan (HA) or chondroitin/dermatan sulfate (CS/DS) occur in many connective tissues, for instance, in bone, cartilage and skin. Due to their significant water-binding capacity, GAG are essential for the biomechanical properties of these tissues. However, there is also increasing evidence that the sulfation of GAG does not occur at random, but a "sulfation code" exists that mediates the physiological functions of GAG. Thus, the biological properties of these biomacromolecules are strongly influenced by the degree of sulfation (ds) and the sulfate group distribution along the polymer. Therefore, certain GAG might also have interesting pharmacological properties. It is, thus, commonly accepted that GAG represent promising biomaterials in the field of tissue engineering as well as to design new bioactive materials for tissue repair and reconstruction. In this review we will focus on chemically sulfated GAG and provide a survey of these compounds on four different levels. First, we will provide an overview on chemical functionalization strategies of naturally occurring HA and CS/DS with special emphasis on regioselective methods to introduce a defined number of sulfate residues into the carbohydrate backbone. Second, chemical and biochemical methods to characterize the synthesized compounds will be introduced with the focus on methods based on nuclear magnetic resonance (NMR) and mass spectrometry (MS). In the third part, we will discuss the interaction of natural and chemically sulfated GAG with proteins and other biomolecules with regulatory functions. Additionally, biological consequences of these interactions regarding healing processes of skin and bone will be presented by discussing selected cell culture experiments. Finally, in vivo effects of GAG as components of artificial extracellular matrices will be discussed.

Poly(L-lactide-co-glycolide) scaffolds coated with collagen and glycosaminoglycans: impact on proliferation and osteogenic differentiation of human mesenchymal stem cells.

In this study, we analyzed poly(L-lactide-co-glycolide) (PLGA) scaffolds modified with artificial extracellular matrices (aECM) consisting of collagen type I, chondroitin sulphate, and sulphated hyaluronan (sHya). We investigated the effect of these aECM coatings on proliferation and osteogenic differentiation of human mesenchymal stem cells (hMSC) in vitro. We found that scaffolds were homogeneously coated, and cross-linking of aECM did not significantly influence the amount of collagen immobilized. Cell proliferation was significantly increased on cross-linked surfaces in expansion medium (EM), but was retarded on cross-linked and non-cross-linked collagen/sHya coatings. The alkaline phosphatase activity was increased on sHya-containing coatings in EM even without the presence of differentiation supplements, but was six to ten times higher in differentiation medium (DM) and comparable for cross-linked and non-cross-linked collagen/sHya. The highest amount of calcium phosphate mineral was deposited on day 28 on cross-linked collagen/sHya. Therefore, coatings of PLGA scaffolds with collagen/sHya promoted the osteogenic differentiation of hMSCs in vitro and might be an interesting candidate for the modification of PLGA for bone reconstruction in vivo.

Sulfated hyaluronan/collagen I matrices enhance the osteogenic differentiation of human mesenchymal stromal cells in vitro even in the absence of dexamethasone.

Glycosaminoglycans (GAG) are multifunctional components of the extracellular matrix (ECM) involved in different steps of the regulation of cellular differentiation. In this study artificial extracellular matrices (aECM) consisting of collagen (Col) I and different GAG derivatives were used as a substrate for human mesenchymal stromal cells (hMSC) to study osteogenic differentiation in vitro. hMSC were cultured on aECM containing col and hyaluronan sulfates (HyaS) with increasing degrees of sulfation (DS(S)) and were compared with aECM containing col and the natural GAG hyaluronan or chondroitin 4-sulfate. hMSC were analyzed for osteogenic differentiation markers such as calcium phosphate deposition, tissue non-specific alkaline phosphatase (TNAP) and expression of runt-related transcription factor 2 (runx2), osteocalcin (ocn) and bone sialoprotein II (bspII). Compared with aECM containing Col and natural GAG all Col/HyaS-containing aECM induced an increase in calcium phosphate deposition, TNAP activity and tnap expression. These effects were also seen in the absence of dexamethasone (an established osteogenic supplement). The expression of runx2 and ocn was not altered and the expression of bspII was diminished on the col/HyaS-containing aECM. The impact of the Col/HyaS-containing aECM on hMSC differentiation was independent of the DS(S) of the HyaS derivatives, indicating the importance of the primary (C-6) hydroxyl group of N-acetylglucosamine. These results suggest that Col/HyaS-containing aECM are able to stimulate hMSC to undergo osteogenic differentiation even in the absence of dexamethasone, which makes these matrices an interesting tool for hMSC-based tissue engineering applications and biomaterial functionalizations to enhance bone formation.

A novel approach for in vitro studies applying electrical fields to cell cultures by transformer-like coupling.

The purpose of this study was to develop a new apparatus for in vitro studies applying low frequency electrical fields to cells without interfering side effects like biochemical reactions or magnetic fields which occur in currently available systems. We developed a non-invasive method by means of the principle of transformer-like coupling where the magnetic field is concentrated in a toroid and, therefore, does not affect the cell culture. Next to an extensive characterization of the electrical field parameters, initial cell culture studies have focused on examining the response of bone marrow-derived human mesenchymal stem cells (MSCs) to pulsed electrical fields. While no significant differences in the proliferation of human MSCs could be detected, significant increases in ALP activity as well as in gene expression of other osteogenic markers were observed. The results indicate that transformer-like coupled electrical fields can be used to influence osteogenic differentiation of human MSCs in vitro and can pose a useful tool in understanding the influence of electrical fields on the cellular and molecular level.

[Bone substitute. Transplants and replacement materials--an update]. / Knochenersatz. Transplantate und Ersatzmaterialien--ein Update.

Due to the special characteristics, autologous bone for bone grafting remains the gold standard for defect filling. Besides allogenic bone transplants, as an alternative a set of bone substitutes has been established. An overview of the bone substitutes presently on the market is almost lost due to the abundance of products. The present paper gives a review of the materials available on the market. Different classification systems regarding origin, vitality, biological priority and chemical composition are described as well as the individual materials including the advantages and disadvantages. Finally, a description of tissue engineering and gene therapy gives a view of future prospective.

The impact of heat treatment on interactions of contact-poled biphasic calcium phosphates with proteins and cells.

A number of studies have reported improved bone integration for calcium phosphate based materials electrically "poled" by an external electric field prior to implantation. In our study we investigated the effects of electrical polarization of a biphasic ceramic composed of 80% hydroxyapatite and 20% ß-tricalcium phosphate. As contact poling involves elevated temperatures as a prerequisite for inducing charge, we used two reference types: samples without any heat treatment and poling, and samples with no poling but heat treatment identical to that of the poled samples. All heat-treated samples (poled or unpoled) showed an improved wettability, which was attributed to a reduced hydrocarbon contamination. Heat treatment alone provoked an accelerated spreading of osteoblast-like cells, whereas on poled samples a retarded cell spreading was observed. While proliferation and several differentiation markers were not influenced by either heat treatment or poling, the release of proinflammatory cytokines interleukin-6 and -8 was significantly reduced for all heat-treated samples, irrespective of additional electrical poling. The study demonstrated that the behaviour of cells in contact with poled biphasic ceramics was influenced by two parameters: heating and charge. Our data revealed that heating of the calcium phosphate ceramics had a much more pronounced effect on cell behaviour than charge.

Angiogenic functionalisation of titanium surfaces using nano-anchored VEGF - an in vitro study.

The aim of the present study was to test the hypothesis that sandblasted and acid etched titanium surfaces can be functionalised with vascular endothelial growth factor (VEGF) using oligonucleotides for anchorage and slow release. rhVEGF165 molecules were conjugated to strands of 30-mer non-coding DNA oligonucleotides (ODN) and hybridised to complementary ODN anchor strands which had been immobilised to the surface of sandblasted/acid etched (SAE) Ti specimens. Specimens with non-conjugated VEGF adsorbed to ODN anchor strands and to blank SAE surfaces served as controls. Specific binding of conjugated VEGF exhibited the highest percentage of immobilised VEGF (71.0 %), whereas non-conjugated VEGF only achieved 53.2 and 30.7 %, respectively. Cumulative release reached 54.0 % of the immobilised growth factor in the group of specifically bound VEGF after 4 weeks, whereas non-conjugated VEGF adsorbed to ODN strands released 78.9% and VEGF adsorbed to SAE Ti surfaces released 97.4 %. Proliferation of human umbilical vein endothelial cells (HUVECs) was significantly increased on the surfaces with specifically bound VEGF compared to the control surfaces and SAE Ti surfaces without VEGF. Moreover, the released conjugated VEGF exhibited biological activity by induction of von Willebrand Factor (vWF) in mesenchymal stem cells. It is concluded that the angiogenic functionalisation of SAE titanium surfaces can be achieved by conjugation of VEGF to ODN strands and hybridisation to complementary ODN strands that are anchored to the titanium surface. The angiogenic effect is exerted both through the immobilised and the released portion of the growth factor.

Sulfated hyaluronan and chondroitin sulfate derivatives interact differently with human transforming growth factor-ß1 (TGF-ß1).

This study demonstrates that the modification of hyaluronan (hyaluronic acid; Hya) and chondroitin sulfate (CS) with sulfate groups leads to different binding affinities for recombinant human transforming growth factor-ß1 (TGF-ß1) for comparable average degrees of sulfation (DS). In general, Hya derivates showed higher binding strength than CS derivatives. In either case, a higher degree of sulfation leads to a stronger interaction. The high-sulfated hyaluronan sHya3 (average DS≈3) exhibited the tightest interaction with TGF-ß1, as determined by surface plasmon resonance and enzyme-linked immunosorbent assay. The binding strength was significantly weakened by carboxymethylation. Unmodified Hya and low-sulfated, native CS showed weak or no binding affinity. The interaction characteristics of the different sulfated glycosaminoglycans are promising for incorporation into bioengineered coatings of biomaterials to modulate growth factor binding in medical applications.

The bone architecture is enhanced with combined PTH and alendronate treatment compared to monotherapy while maintaining the state of surface mineralization in the OVX rat.

This study examined the effect of PTH and alendronate alone and in combination on the bone architecture, mineralization, and estimated mechanics in the OVX rat. Female Wistar rats aged 7-9months were assigned to one of five groups: (1) sham+vehicle, (2) OVX+vehicle, (3) OVX+PTH, (4) OVX+alendronate, and (5) OVX+PTH and alendronate. Surgery was performed at baseline (week 0), and biweekly treatment (15µg/kg of alendronate and/or daily (5days/week) 40µg/kg hPTH(1-34)) was administered from week 6 to week 14. Micro-CT scans of the right proximal tibial metaphysis were made in vivo at weeks 0, 6, 8, 10, 12 and 14 and measurements of bone microarchitecture and estimated mechanical parameters (finite element analysis) were made from the images. Synchrotron radiation micro-CT scans of the proximal tibia and fourth lumbar vertebrae were conducted ex vivo at the study endpoint to determine the degree and spatial distribution of the bone mineralization. Alendronate preserved the microarchitecture after OVX, and increased cortical (9%, p<0.05) and trabecular thickness (5%, p<0.05). PTH mono- and combined therapy induced increases in cortical (25-35%, p<0.05) and trabecular thicknesses (46-48%, p<0.05), resulting in a full restoration of bone volume in the PTH group, and an increase beyond baseline in the combined group. Improvements in estimated mechanical outcomes were observed in all treatment groups by the end of the study, with the combined group experiencing the greatest increase in predicted stiffness (63%, p<0.05). Alendronate treatment increased the peak mineral content above the other treatment groups at the trabecular (tibia: 6% above PTH, 6% above combined, L4: 4% above PTH, 4% above combined) and endocortical (tibia: 4% above PTH, 3% above combined, L4: 1% above PTH, 2% above combined) surfaces, while no differences in mineralization between the PTH and combined groups were observed. Combined treatment resulted in more pronounced improvements of the bone architecture than PTH monotherapy, while maintaining the state of mineralization observed with PTH treatment.

Ovine bone marrow mesenchymal stem cells: isolation and characterization of the cells and their osteogenic differentiation potential on embroidered and surface-modified polycaprolactone-co-lactide scaffolds.

The current study was undertaken with the goal being isolation, cultivation, and characterization of ovine mesenchymal stem cells (oMSC). Furthermore, the objective was to determine whether biological active polycaprolactone-co-lactide (trade name PCL) scaffolds support the growth and differentiation of oMSC in vitro. The oMSC were isolated from the iliac crest of six merino sheep. Three factors were used to demonstrate the MSC properties of the isolated cells in detail. (1) Their ability to proliferate in culture with a spindle-shaped morphology, (2) presence of specific surface marker proteins, and (3) their capacity to differentiate into the three classical mesenchymal pathways, osteoblastic, adipogenic, and chondrogenic lineages. Furthermore, embroidered PCL scaffolds were coated with collagen I (coll I) and chondroitin sulfate (CS). The porous structure of the scaffolds and the coating with coll I/CS allowed the oMSC to adhere, proliferate, and to migrate into the scaffolds. The coll I/CS coating on the PCL scaffolds induced osteogenic differentiation of hMSC, without differentiation supplements, indicating that the scaffold also has an osteoinductive character. In conclusion, the isolated cells from the ovine bone marrow have similar morphologic, immunophenotypic, and functional characteristics as their human counterparts. These cells were also found to differentiate into multiple mesenchymal cell types. This study demonstrates that embroidered PCL scaffolds can act as a temporary matrix for cell migration, proliferation, and differentiation of oMSC. The data presented will provide a reliable model system to assess the translation of MSC-based therapy into a variety of valuable ovine experimental models under autologous settings.

How is wettability of titanium surfaces influenced by their preparation and storage conditions?

The effect of two different etching procedures with inorganic acids (HSE and CSE)-one using additionally strongly oxidising conditions due to the presence of CrO(3) (CSE)-and consecutive storage conditions (dry methanol and air) for previous corundum blasted titanium surfaces is compared with respect to their wettability behaviour and the potential of the etching processes for removing remaining blasting material. The etching procedures result in distinct different surface morphologies. Whereas the HSE surface shows sub-mm to sub-mum structures but neither porosity nor undercuts, the CSE surface is extremely rugged and porous with structures protruding the more homogeneously attacked areas by several micrometers. By EDX analysis both remaining blasting material and chromium and sulphur from the etching treatment has been detected on the CSE surfaces only. Both surfaces states show super-hydrophilic behaviour immediately after etching and storage up to 28 days in dry methanol. Whereas contact with air does not change super-hydrophilicity for the CSE samples, wettings angles of the HSE samples increase within minutes and reach about angles of about 60 degrees and 90 degrees after one and 2 days exposure to air, respectively. The increasing hydrophobicity is discussed with respect to the formation of a surface coverage from hydrocarbons originating from aromatic compounds present in traces in air.

Effect of modifications of dual acid-etched implant surfaces on peri-implant bone formation. Part I: organic coatings.

OBJECTIVE: The aim of the present study was to test the hypothesis that peri-implant bone formation can be improved by modifying dual acid-etched (DAE) implant surfaces using organic coatings that enhance cell adhesion and osteogenic differentiation. MATERIAL AND METHODS: Ten adult female foxhounds received experimental titanium implants in the mandible 3 months after removal of all premolar teeth. Six types of implants were evaluated in each animal: (i) implants with a machined surface (MS), (ii) implants with a DAE surface topography, (iii) implants with an acid-etched surface coated with RGD peptides, (iv) implants with an acid-etched surface coated with collagen I, (v) implants with an acid-etched surface coated with collagen I and chondroitin sulphate (CS), (vi) implants with an acid-etched surface coated with collagen I and CS and recombinant human bone morphogenetic protein-2. Peri-implant bone regeneration was assessed by histomorphometry after 1 and 3 months in five dogs each by measuring bone implant contact (BIC) and the bone volume density (BVD) of the newly formed peri-implant bone. RESULTS: After 1 month, mean BIC was significantly higher in the coated implants group than in the MS group. There was no significant difference when mean BIC in the DAE group was compared with implants with any of the organic coatings, but the difference was significant when compared with the MS implants. Differences in mean BVD value did not reach significance between any of the surfaces. After 3 months, the same held true for the mean BIC of all the groups except for Coll I. Mean volume density of the newly formed bone was higher in all the surface modifications, albeit without statistical significance. CONCLUSIONS: It is concluded that with the exception of Coll I, the tested organic surface coatings on DAE surfaces did not improve peri-implant bone formation when compared with the DAE surfaces but enhanced BIC when compared with the MSs.

Effect of modifications of dual acid-etched implant surfaces on periimplant bone formation. Part II: calcium phosphate coatings.

The aim of the present study was to test the hypothesis that calcium phosphate coatings of dual acid-etched surfaces (DAEs) can improve periimplant bone regeneration. Ten adult female foxhounds received experimental titanium screw implants in the mandible 3 months after removal of all premolar teeth. Five types of surface states were evaluated in each animal: (i) implants with a machined surface (MS) (Control 1); (ii) implants with a DAE (Control 2); (iii) implants with a DAE coated with collagen I (Control 3); (iv) implants with a DAE with mineralized collagen I; and (v) implants with a DAE with a hydroxylapatite (HA) coating. Periimplant bone regeneration was assessed by histomorphometry after 1 and 3 months in five dogs each by measuring bone implant contact (BIC) and the volume density of the newly formed periimplant bone (BVD). After 1 month, mean BIC of experimental implants did not differ significantly from implants with DAE and collagen-coated surfaces, but was significantly higher than the MS implants. BVD was enhanced significantly only in implants with mineralized collagen coating compared with DAE and collagen-coated controls. After 3 months, the mean values of BIC had increased significantly in the group of implants with HA and mineralized collagen coating but were not significantly different from implants with DAE and collagen-coated surfaces. The same held true for the mean BVD values. In conclusion, the present study could not verify the hypothesis that calcium phosphate coatings of DAEs in the present form enhanced periimplant bone formation compared with the DAE surface alone.

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

Advanced surface modifications and materials were tested on the same implant geometry. Six types of dental implants were tested for osseointegration after 2, 4 and 8 weeks in a sheep pelvis model. Four titanium implant types were treated with newly developed surface modifications, of which two were chemically and two were pharmacologically modified. One implant was made of zirconia. A sandblasted and acid-etched titanium surface was used as reference. The chemically modified implants were plasma-anodized or coated with calcium phosphate. The pharmacological coatings contained either bisphosphonate or collagen type I with chondroitin sulphate. The implants were evaluated using macroscopic, radiographic and 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 was better (77%). The main BIC increase was between 2 and 4 weeks. The pharmacologically coated implants (78-79%) and the calcium phosphate coating (83%) showed similar results compared with the reference implant (80%) at 8 weeks. There were no significant differences in BIC. Compared with previous studies the results of all implants were comparatively good.