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.

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.

[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.

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.

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.

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.

Evaluation of osseointegration of dental implants coated with collagen, chondroitin sulphate and BMP-4: an animal study.

Various studies have shown type I collagen (coll) to increase bone-implant contact (BIC) compared to uncoated implants. The aim of this animal study was to test whether the integration of chondroitin sulphate (CS) and the growth factor rhBMP-4 into a collagenous coating could further increase the measured BIC compared to collagen coated implants alone. The experimental implants had two recesses along the length axis. 120 implants with the surface modifications: coll, coll/CS, coll/CS/rhBMP-4 were inserted into the mandible of 20 minipigs. Six months after implantation, BIC was measured histomorphometrically on the surface and within the recesses. Due to the specific animal model and strict criteria in placement, 39.2 % of the implants were considered as failure and not included in the analysis. Of the successfully gained 73 implants, the highest percentage of BIC was obtained for coll/CS (40%), followed by coll (30%) and coll/CS/rhBMP-4 (27%), P=0.013. BIC within the recesses was highest for coll/CS (51%), followed by coll (43%) and coll/CS/rhBMP-4 (34%), P=0.025. The result suggests that the inclusion of CS slightly increases the BIC compared to collagen coated implants. The further inclusion of a low amount rhBMP-4 had a detrimental effect on bone formation compared to coll/CS, P<0.05.

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.

Fibrils of different collagen types containing immobilised proteoglycans (PGs) as coatings: characterisation and influence on osteoblast behaviour.

Collagen, the main organic component of bone, is used as a coating on titanium implants and as a scaffold material in bone tissue engineering. Surface modifications of titanium which promote osteoblast adhesion, proliferation and synthesis of collagen by osteoblasts are desirable. One biomimetic approach is the coating of titanium with collagen in fibrillar form. Other organic components of bone may be bound to fibrils and exert additional effects. In this study, the collagen types I-III were compared regarding their ability to bind the proteoglycans decorin and biglycan, which are found in bone. More collagen was bound to collagen II fibrils than to those of types I and III. Therefore, titanium surfaces were coated with fibrils of collagen type II containing biglycan or decorin or neither to investigate the effect of the proteoglycans on human primary osteoblast behaviour. In addition, the growth factor TGF-beta1 was adsorbed onto surfaces coated with fibrils of collagen type II containing biglycan or decorin or neither to investigate the influence of decorin and biglycan on the effect of TGF-beta1 on osteoblasts. Fibril-bound biglycan and decorin influence primary osteoblast behaviour by themselves. The presence of substrate-bound biglycan or decorin influences the effect of TGF-beta1. These results may be important when designing collagen-based coatings or scaffolds for tissue engineering, including those loaded with growth factors.

Surface modification of titanium-based alloys with bioactive molecules using electrochemically fixed nucleic acids.

A new method of surface modification for titanium (alloys) with bioactive molecules was developed with the intention of providing a new basis of implant adaptation for particular requirements of certain medical indications. Nucleic acid single strands are fixed electrochemically via their termini (regiospecifically) by growing an oxide layer on Ti6Al7Nb anodically. It could be shown that they are accessible to subsequent hybridization with complementary strands at physiological pH. Amount of nucleic acids immobilized and hybridized were determined radioanalytically using 32P-labelled nucleic acids. Stable fixation was attained at and above potentials of 4 V(SCE). Up to 4 pmol/cm2 of nucleic acid single strands could be immobilized and hybridization efficiencies up to 1.0 were reached. Hybridization efficiency was found to depend on surface density of immobilized oligonucleotides, while hybridization rates increased when MgCl2 was added. A conjugate consisting of an oligonucleotide complementary to the immobilized strand and the hexapeptide GRGDSP with RGD as an integrin recognition site was synthesized. This conjugate was able to bind to integrins on osteoblasts. It was shown that this conjugate binds to the anchor strand fixed on Ti6Al7Nb to an extent comparable with the unconjugated complementary strand.

Functionalization of dental implant surfaces using adhesion molecules.

The aim of the present study was to test the hypothesis that organic coating of titanium screw implants that provides binding sites for integrin receptors can enhance periimplant bone formation. Ten adult female foxhounds received experimental titanium screw implants in the mandible 3 months after removal of all premolar teeth. Four types of implants were evaluated in each animal: (1) implants with machined titanium surface, (2) implants coated with collagen I, (3) implants with collagen I and cyclic RGD peptide coating (Arg-Gly-Asp) with low RGD concentrations (100 micromol/mL), and (4) implants with collagen I and RGD coating with high RGD concentrations (1000 micromol/mL). Periimplant bone regeneration was assessed histomorphometrically 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, BIC was significantly enhanced only in the group of implants coated with the higher concentration of RGD peptides (p = 0.026). Volume density of the newly formed periimplant bone was significantly higher in all implants with organic coating. No significant difference was found between collagen coating and RGD coatings. After 3 months, BIC was significantly higher in all implants with organic coating than in implants with machined surfaces. Periimplant BVD was significantly increased in all coated implants in comparison to machined surfaces also. It was concluded that organic coating of machined screw implant surfaces providing binding sites for integrin receptors can enhance bone implant contact and periimplant bone formation.

Transforming growth factor beta1 immobilized adsorptively on Ti6Al4V and collagen type I coated Ti6Al4V maintains its biological activity.

Titanium and titanium alloys are often used for orthopedic and dental implants. Osseointegration of Ti6Al4V may be improved not only by precoating of the surface with extracellular matrix proteins like collagen type I but also by additional immobilization of growth factors. In the present study, transforming growth factor beta1 (TGF-beta1) which is known as an inducer of collagen synthesis was immobilized adsorptively on uncoated and collagen type I coated Ti6Al4V surfaces. TGF-beta1 was found immobilized slightly faster to collagen type I coated than to uncoated Ti6Al4V and released slower from the collagen coated material. Immobilized TGF-beta1 is biologically active for at least 3 weeks storage at 4 degrees C. Sterilization by ethylene oxide inactivates immobilized TGF-beta1. In osteoblasts cultured on implants with adsorptively immobilized TGF-beta1, mRNA level and specific catalytic activity of alkaline phosphatase as well as accumulation of calcium and phosphate were found reduced, whereas procollagen alpha1(I) mRNA level and the rate of collagen synthesis were increased.

Comparison of microfocus- and synchrotron X-ray tomography for the analysis of osteointegration around Ti6Al4V implants.

Micro-computed tomography (microCT) provides quantitative three-dimensional information of bone around titanium implants similar to classical histology. The study, based on an animal model, containing cuboid-shaped biofunctionalised Ti6Al4V implants with surrounding bone after 4 weeks, is performed using 3 microCT-systems with X-ray tubes, one synchrotron-radiation-based microCT-system (SRmicroCT), and classical histology. Although the spatial resolution of the microCT-systems is comparable, only the results of SRmicroCT agree with results of classical histology. The X-ray tube sources give rise to huge artefacts in the tomograms (interface scattering, beam hardening), which impaired the quantitative analysis of bone up to about 200microm from the implant surface. Due to the non-destructive character of microCT the specimens can be subsequently examined by classical histology without restriction. The quantitative comparison of bone formation uncovers the strong dependence of the newly formed bone from the selected slice. This implies the necessity of 3D analysis. SRmicroCT and classical histology prove that surface modifications of the titanium implant significantly influence the bone formation. Using SRmicroCT, the preparation artefacts due to cutting and polishing are excluded.

Electrochemically assisted deposition of thin calcium phosphate coatings at near-physiological pH and temperature.

An electrochemical method for the deposition of calcium phosphate phases on titanium surfaces using the galvanostatic mode is presented. Deposition was performed in a (Ca(2+) / H(x)PO(4) ((3-x)-))-containing electrolyte near physiological conditions with regard to pH (6.4) and temperature (36 degrees C). Cathodic alkalization leads first to the formation of a thin homogeneous layer that shows a nanoscale surface topography of alternating wall-like elevations and channels. It is thought that these channels in the calcium phosphate prelayer are formed as pathways for hydroxyl ions and hydrogen. Upon this layer, spheres of amorphous calcium phosphate (ACP) are formed as indicated by Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy. According to transmission electron microscopy images, these spheres consist of small clusters of calcium phosphate (approximately 30 nm) and can grow up to 300 nm in diameter. Characteristic for this ACP is a high water content as seen by FTIR. As a function of current density, the ACP is then transformed into crystalline hydroxyapatite (HAP), which was identified using FTIR and X-ray diffraction. The morphology of the HAP crystals can be described as needles with dimensions of <500-nm length and <60-nm width. By choice of different electrochemical parameters, a homogeneous coating of either ACP, HAP, or the intermediate phase can be achieved, as shown in a kinetic phase diagram, thus allowing the formation of coatings with different properties in solubility and morphology.

Biological performance of biomimetic calcium phosphate coating of titanium implants in the dog mandible.

The aim of the present study was to analyze the in vivo effect of biomimetic calcium phosphate coating of titanium implants on periimplant bone formation and bone-/implant contact. Five types of implants were used: 1) Ti6Al4V implants with a polished surface; 2) Ti6Al4V implants with collagen coating; 3) Ti6Al4V implants with a mineralized collagen layer; 4) Ti6Al4V implants with sequential coating of hydroxyapatite (HA) and collagen; and 5) Ti6Al4V implants with HA coating only. All implants had square cross sections with an oblique diameter of 4.6 mm and were inserted press fit into trephine burr holes of 4.6 mm in the mandibles of ten beagle dogs. The implants of five animals each were evaluated after a healing period of 1 month and 3 months, respectively, during which time sequential fluorochrome labeling of bone formation had been performed. Bone formation was evaluated by morphometric measurement of the newly formed bone around the implants and the percentage of implant bone contact. After 1 month, there was a significantly higher percentage of mean bone/implant contact in the HA-coated implants compared to those with polished surface and those with the collagen-coated surface. After 3 months, these differences were not present anymore. Bone apposition was significantly higher next to implants with sequential HA/collagen coating compared to polished surfaces and mineralized collagen layer. It is concluded that biomimetic coating of titanium implants with HA has shown the clearest trend to increase bone-implant contact in the early ingrowth period. The addition of collagen to an HA coating layer may hold some promise when used as sequential HA/collagen coating with mineralized collagen as the surface layer.

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.

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.

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.