Does the Choice of Preparation Protocol for Platelet-Rich Fibrin Have Consequences for Healing and Alveolar Ridge Preservation After Tooth Extraction? A Meta-Analysis.

PURPOSE: Multiple preparation protocols for platelet-rich fibrin (PRF) are in use today, and clinical results are often heterogeneous. This study analyzes the impact of the chosen PRF preparation protocol on 1) wound healing and 2) alveolar ridge preservation. METHODS: For this systematic review and meta-analysis, eligible studies were identified in PubMed and Cochrane databases. Included were randomized controlled and controlled clinical trials with healthy patients treated with PRF after atraumatic tooth extraction compared to untreated socket(s), reporting at least one of the following outcome variables: pain, swelling, soft tissue healing, alveolar osteitis risk, horizontal and vertical bone loss, socket fill, and new bone formation. Main predictor variable was relative centrifugal force (RCF) comparing high RCF (high PRF), intermediate RCF (standard [S-PRF]), low RCF (advanced PRF), and various RCF settings (concentrated growth factor preparation [CGF]). The type of centrifugation tubes (silica-coated plastic and glass) was a secondary predictor. Weighted or standardized mean differences, risk ratio and corresponding 95% confidence intervals were calculated. RESULTS: Forty studies published between 2012 and 2022 were selected. The pooled effects of all outcomes were significant against untreated sockets. Within the subgroups high PRF or advanced PRF had the lowest efficacy for many outcome parameters. Pain reduction (in visual analog scale units) was highest for S-PRF (-1.18 [-1.48, -0.88], P < .00001) and CGF (-1.03 [-1.16, -0.90], P < .001). The risk ratio of alveolar osteitis (0.09 [0.01, 0.69], P < .02) and soft tissue healing (standardized mean difference = 2.55 [2.06, 3.03], P < .001) were best for CGF. No subgroup differences were found for bone-related outcomes. No meaningful analysis of the tube material effect was possible. CONCLUSION: This study confirms that PRF is associated with reduced postoperative complications but indicates that preparation protocol influences clinical outcomes. S-PRF and CGF protocols appear to be superior for several outcome parameters.

Osseointegration--communication of cells.

BACKGROUND: The article provides the scientific documentation for the 3D animated film - "Osseointegration - Communication of cells". AIM: The aim of this article and of the film is to visualise the molecular and cellular events during the healing of an osseous wound after installation of a dental implant with special emphasis on the process of osseointegration. MATERIAL AND RESULTS: In this review article for didactic reasons the concept of the four phases of a healing soft tissue wound was transferred to a bone wound after insertion of a dental implant: haemostasis, inflammatory phase, proliferative phase and remodelling phase. Wound healing throughout these phases is the result of a coordinated action of different cell types which communicate with each other by their interaction using signalling molecules like cytokines, extracellular matrix proteins and small molecules. A regular sequence of cell types controlled by adequate concentrations of signalling molecules results in undisturbed healing. Disturbed healing is associated with a continuation of the early inflammatory phase and the development of a toxic wound environment. The latter is characterized by high counts of polymorphnuclear cells, high concentrations of toxic radicals and proteolytic enzymes and low concentrations of growth factors and extracellular matrix molecules. Clinically the development of a toxic wound environment should be avoided, e.g. by antibacterial measures. DISCUSSION AND CONCLUSION: Experiencing implant osseointegration as a biological process may provide the clinician new targets to improve the therapy with dental implants.

A systematic review on the effect of inorganic surface coatings in large animal models and meta-analysis on tricalcium phosphate and hydroxyapatite on periimplant bone formation.

The aim of the present systematic review was to analyse studies using inorganic implant coatings and, in a meta-analysis, the effect of specifically tricalcium phosphate (TCP) and hydroxyapatite (HA) implant surface coatings on bone formation according to the PRISMA criteria. Inclusion criteria were the comparison to rough surfaced titanium implants in large animal studies at different time points of healing. Forty studies met the inclusion criteria for the systematic review. Fifteen of these analyzed the bone-to-implant contact (BIC) around the most investigated inorganic titanium implant coatings, namely TCP and HA, and were included in the meta-analysis. The results of the TCP group show after 14 days a BIC being 3.48% points lower compared with the reference surface. This difference in BIC decreases to 0.85% points after 21-28 days. After 42-84 days, the difference in BIC of 13.79% points is in favor of the TCP-coatings. However, the results are not statistically significant, in part due to the fact that the variability between the studies increased over time. The results of the HA group show a significant difference in mean BIC of 6.94% points after 14 days in favor of the reference surface. After 21-28 days and 42-84 days the difference in BIC is slightly in favor of the test group with 1.53% points and 1.57% points, respectively, lacking significance. In large animals, there does not seem to be much effect of TCP-coated or HA-coated implants over uncoated rough titanium implants in the short term.

Outcomes and Stability of Anterior Open Bite Treatment with Skeletal Anchorage in Non-Growing Patients and Adults Compared to the Results of Orthognathic Surgery Procedures: A Systematic Review.

The objective of this review is to evaluate, on the basis of the available literature, if anterior open bite (AOB) can be successfully treated with the intrusion of molar teeth using skeletal anchorage in non-growing patients and adults and if this treatment modality provides comparable results to those obtained by orthognathic surgery procedures. METHODS: A systematic review of published data in major databases from 2000 to 2021 was performed. RESULTS: In total, 92 articles were included in title and abstract screening, and only 16 articles (11 concerning AOB correction by molar intrusion with skeletal anchorage, and five considering AOB treatment by orthognathic surgical intervention) qualified for thorough data extraction and analysis. CONCLUSIONS: On the basis of this review, it seems to be possible to obtain successful results for AOB treatment in non-growing patients and adults by means of the intrusion of molar teeth with skeletal anchorage. However, due to the different methods of assessing treatment outcomes used by different authors, it is not possible to state conclusively whether the treatment of AOB by means of molar intrusion with skeletal anchorage provides long-term results that are comparable to orthognathic surgery procedures.

Glucuronic acid and phosphoserine act as mineralization mediators of collagen I based biomimetic substrates.

Glucuronic acid (GlcA) and phosphoserine (pS) carrying acidic functional groups were used as model molecules for glycosaminoglycans and phosphoproteins, respectively to mimic effects of native biomolecules and influence the mineralization behaviour of collagen I. Collagen substrates modified with GlcA showed a stable interaction between GlcA and collagen fibrils. Substrates were mineralized using the electrochemically assisted deposition (ECAD) in a Ca(2+)/H( x )PO (4) ((3-x)) electrolyte at physiological pH and temperature. During mineralization of collagen-GlcA matrices, crystalline hydroxyapatite (HA) formed earlier with increasing GlcA content of the collagen matrix, while the addition of pS to the electrolyte succeeded in inhibiting the transformation of preformed amorphous calcium phosphate (ACP) to HA. The lower density of the resulting mineralization and the coalesced aggregates formed at a certain pS concentration suggest an interaction between calcium and the phosphate groups of pS involving the formation of complexes. Combining GlcA-modified collagen and pS-modified electrolyte showed dose-dependent cooperative effects.

Success and side effects of different treatment options in the low current attack of bacterial biofilms on titanium implants.

The long-term success of peri-implantitis treatments is generally insufficient. Attacking the bacteria on the titanium implant surface using electrochemical polarization could be an alternative approach. In this study an E. coli biofilm in phosphate buffered saline was treated with low current densities (0.25 to 2 mA/cm2) using anodic, cathodic, or combined polarization regimes, either alone or with the antiseptic chlorhexidine. The antibacterial effect was assessed using LIVE/DEAD® staining and through quantification of viable bacteria, sample surfaces were characterized pre- and post-treatment with electrochemical impedance spectroscopy. All polarization treatments had an antibacterial effect that increased with current density, with at least 1 mA/cm2 necessary to reduce colony forming units by four orders of magnitude. Cathodic treatment was slightly superior to anodic treatment, and there was no difference between alternating polarization and single-type polarization. Neither treatment resulted in a significant detachment of bacteria, but combination with chlorhexidine improved the antibacterial effect synergistically. The use of chloride containing electrolytes is not recommended in this context. The low current densities used here were not sufficient to generate adequate bactericidal chlorine reactive species, but first signs of pitting corrosion were already detected for anodic polarization at 1 mA/cm2.

Modifications of hyaluronan influence the interaction with human bone morphogenetic protein-4 (hBMP-4).

In this study, we have demonstrated that the modification of hyaluronan (hyaluronic acid; Hya) with sulfate groups led to different binding affinities for recombinant human bone morphogenetic protein-4 (rhBMP-4). The high-sulfated sHya2.8 (average degree of sulfation (D.S.) 2.8) exhibited the tightest interaction with rhBMP-4, followed by the low-sulfated sHya1.0, as determined with surface plasmon resonance (SPR), ELISA, and competition ELISA. Unmodified Hya, chondroitin-sulfate (CS), and heparan sulfate (HS) showed significantly less binding affinity. SPR data could be fitted to an A + B = AB Langmuir model and binding constants were evaluated ranging from 13 pM to 5.45 microM. The interaction characteristics of the differentially sulfated Hyas are promising for the incorporation of these modified polysaccharides in bioengineered coatings of biomaterials for medical applications.

Increased bone formation around coated implants.

AIM: We hypothesized that coating threaded, sandblasted acid-etched titanium implants with collagen and chondroitin sulphate (CS) increases bone formation and implant stability, compared with uncoated controls. MATERIALS AND METHODS: Three different implant surface conditions were applied: (1) sandblasted acid-etched (control), (2) collagen/chondroitin sulphate (low-dose--CS1), (3) collagen/chondroitin sulphate (high-dose--CS2). Sixty 9.5 mm experimental implants were placed in the mandible of 20 minipigs. Bone-implant contact (BIC) and relative peri-implant bone-volume density (rBVD--relation to bone-volume density of the host bone) were assessed after 1 and 2 months of submerged healing. Implant stability was measured by resonance frequency analysis (RFA). RESULTS: After 1 month, coated implants had significantly more BIC compared with controls (CS1: 68%, p<0.0001, CS2: 63%, p=0.009, control: 52%). The rBVD was lower for all surface conditions, compared with the hostbone. After 2 months, BIC increased for all surfaces. No significant differences were measured (CS1: 71%, p=0.016, CS2: 68%, p=0.67, control: 63%). The rBVD was increased for coated implants. RFA values were 71-77 at implantation, 67-73 after 1 month and 74-75 after 2 months. Differences in rBVD and RFA were not statistically significant. CONCLUSIONS: Data analysis suggests that collagen/CS has a positive influence on bone formation after 1 month of endosseous healing.

Biomechanical comparison of different surface modifications for dental implants.

PURPOSE: A satisfactory clinical outcome in dental implant treatment relies on primary stability for immediate load bearing. While the geometric design of an implant contributes to mechanical stability, the nature of the implant surface itself is also critically important. Biomechanical and microcomputerized tomographic evaluation of implant osseointegration was performed to compare alternative structural, chemical and biochemical, and/or pharmaceutical surface treatments applied to an identical established implant design. MATERIALS AND METHODS: Dental implants with the same geometry but with 6 different surface treatments were tested in vivo in a sheep model (pelvis). Peri-implant bone density and removal torque were compared at 2, 4, and 8 weeks after implantation. Implant surfaces tested were: sandblasted and acid-etched titanium (Ti), sandblasted and etched zirconia, Ti coated with calcium phosphate (CaP), Ti modified via anodic plasma-chemical treatment (APC), bisphosphonate-coated Ti (Ti + Bisphos), and Ti coated with collagen containing chondroitin sulfate (CS). RESULTS: All dental implants were well integrated at the time of sacrifice. There were no significant differences observed in peri-implant bone density between implant groups. After 8 weeks of healing, removal torque values for Ti, Ti + CaP, Ti + Bisphos, and Ti + collagen + CS were significantly higher than those for zirconia and Ti + APC. CONCLUSIONS: Whereas the sandblasted/acid-etched Ti implant can still be considered the reference standard surface for dental implants, functional surface modifications such as bisphosphonate or collagen coating seem to enhance early peri-implant bone formation and should be studied further.

Utilizing DNA for functionalization of biomaterial surfaces.

DNA sequences are widely used for gene transfer into cells including a number of substrate surface-based supporting systems, but due to its singular structure property profile, DNA also offers multiple options for noncanonical applications. The special case of using DNA and oligodeoxyribonucleotide (ODN) structures for surface functionalization of biomedical implants is summarized here with the major focus on (a) immobilization or anchoring of nucleic acid structures on substrate surfaces, (b) incorporation of biologically active molecules (BAM) into such systems, and (c) biological characteristics of the resulting surfaces in vitro and in vivo. Sterilizations issues, important for potential clinical applications, are also considered.

Osteogenic nanostructured titanium surfaces with antibacterial properties under conditions that mimic the dynamic situation in the oral cavity.

The study aim was to assess the impact of different surface nanofeatures on otherwise smooth titanium surfaces on bacterial adhesion as well as on their osteogenic potential. Bacterial adhesion was assessed in the presence of saliva under static and dynamic conditions to approximate both sub- and supragingival conditions in the oral cavity as the gingival seal will be affected by implantation. The ultimate goal was to develop a surface that will reduce biofilm formation but still support osseointegration in vivo. To this end nanotubular or nanopitted surfaces were created on electropolished titanium via electrochemical anodization procedures. Sandblasted/acid etched surfaces (SBAE) were used as a microrough reference. Bacterial adhesion was studied using saliva-precoated samples with S. sanguinis as a typical early colonizer of the oral cavity; osteogenic differentiation was assessed with human bone marrow stromal cells. While bacterial adhesion was reduced on all microsmooth surfaces to an average of 17% surface coverage compared to 61% on SBAE under static conditions, under dynamic conditions the nanopitted surface had a significant impact on bacterial adhesion. Here fluid flow removed all bacteria. By comparison, the reduction on the nanotubular surface was only similar to that of the SBAE reference. We hypothesise the underlying cause to be an effect of the surface morphology on the structure and composition of the saliva precoating that reduces its stability, giving rise to a self-cleaning effect. In addition, no negative influence on the osteogenic potential of the nanopitted surface could be determined by alkaline phosphatase activity, mineralization behaviour or gene expression; it remained on a par with the tissue culture plastic control. Thus, nanopitting seems to be a promising surface treatment candidate for dental implants to reduce infection related complications without compromising the implant integration.

In vivo effects of coating loaded and unloaded Ti implants with collagen, chondroitin sulfate, and hydroxyapatite in the sheep tibia.

The in vivo effects of coating titanium implants with organic extracellular matrix molecules were examined in the sheep tibia. Titanium screws (5.0 mm) were coated with type I collagen (Ti/Coll) or type I collagen and chondroitin sulfate (Ti/Coll/CS) by biomimetic fibrillogenesis. Uncoated screws (Ti) and screws coated with hydroxyapatite (Ti/HA) served as control. Six adult female sheep received one screw of each type to stabilize a midshaft tibial fracture with external fixation. Four cylindrical implants of 4-mm outer diameter and 3.3-mm inner diameter with the same coatings were inserted into the tibial head. No pin track infections were seen at the time of implant retrieval 6 weeks after implantation. Extraction torque was greater for Ti/HA (1181 Nmm) and Ti/Coll/CS (1088 Nmm) compared to Ti/Coll (900 Nmm) and Ti (904 Nmm) [N.S.]. Newly formed bone was noted around all coated screws within the medullary cavity. Macrophage and osteoclast activity was significantly reduced around Ti/Coll/CS in both types of implants compared to uncoated controls (p < 0.05). Osteoblast activity was significantly increased around loaded Ti/Coll and Ti/Coll/CS screws compared to uncoated Ti screws (p < 0.05). Microtomographic evaluation (SRmicroCT) revealed no significant differences in new bone formation around the unloaded tibial head implants. Coating of external fixation devices with of type I collagen and chondroitin sulfate appears to have similar effects with respect to stability and bone healing as HA but with less osteoclast activity. These findings were more pronounced under loaded than unloaded conditions in the sheeptibia.

Influence of extracellular matrix coatings on implant stability and osseointegration: an animal study.

Aim of the present study was to test the hypothesis that the application of components of the extracellular matrix such as glycosaminoglycans used as implant surface coatings in combination with collagen, with and without growth factor, can lead to enhanced ossification and thus improve implant stability compared with collagen coatings alone. Twenty miniature pigs received 120 experimental titanium implants in the mandible. Three types of surface coatings were created: (1) collagen type I (coll), (2) collagen type I/chondroitin sulphate (coll/CS), (3) collagen type I/chondroitin sulphate/BMP-4 (coll/CS/BMP). Periimplant bone formation was assessed within a defined recess along the length axis of the implant. Bone-implant contact (BIC) and bone volume density (BVD) were determined, using both histomorphometry and synchrotron radiation micro computed tomography (SRmicroCT). To measure implant stability, resonance frequency analysis was applied after implantation and 1, 3, 7, and 22 weeks after placement. BIC was highest for coll/CS coated implants, followed by coll, p = 0.082. Histomorphometric BVD did not significantly change for any coating. SRmicroCT analysis showed an increased BVD for collagen coated implants, compared with the other two surface coatings. Implant stability showed a decrease for all coatings up to the third week. At 22 weeks, all coatings showed an increase in stability without reaching their initial level. Highest stability was reached for coll coated implants, p = 0.051. It was concluded that collagen and coll/CS implant coatings have advantageous characteristics for peri-implant bone formation, compared with the further integration of BMP-4.

Coating of titanium implants with collagen, RGD peptide and chondroitin sulfate.

Coating of orthopaedic implants with extracellular bone matrix components was performed to enhance bone healing. Titanium pins of 0.8mm diameter were coated with type I collagen (Ti/Coll), RGD peptide (Ti/RGD) or type I collagen and chondroitin sulfate (Ti/Coll/CS). Uncoated pins (Ti) served as control. The pins were inserted as intramedullary nails into the tibia of male adult Wistar rats. Six specimens of each group were retrieved at 4, 7, 14 and 28 days. All implants healed uneventfully without adverse reactions. ED 1-positive macrophages appeared in higher numbers around Ti/RGD at day 4 and around Ti at day 14 after implantation (p < 0.05). TRAP-positive osteoclasts and precursors were abundant around Ti/Coll/CS at day 7 (p < 0.05). A significant increase in osteopontin-positive osteoblasts was seen around Ti/Coll/CS implants at days 7 and 14, and around Ti/RGD at day 14 (p < 0.05). At day 28, 62% of Ti, 76% of Ti/Coll, 85%* of Ti/RGD and 89%* of Ti/CoIl/CS (*p < 0.05) implants were covered with newly formed lamellar bone. The addition of extracellular matrix components significantly enhances bone remodelling in the early stages of bone healing around Ti implants, eventually leading to increased new bone formation at the implant surface after 4 weeks.

Collageneous matrix coatings on titanium implants modified with decorin and chondroitin sulfate: characterization and influence on osteoblastic cells.

Studies in developmental and cell biology have established the fact that responses of cells are influenced to a large degree by morphology and composition of the extracellular matrix. Goal of this work is to use this basic principle to improve the biological acceptance of implants by modifying the surfaces with components of the extracellular matrix (ECM), utilizing the natural self-assembly potential of collagen in combination with further ECM components in close analogy to the situation in vivo. Aiming at load-bearing applications in bone contact, collagen type I in combination with the proteoglycan decorin and the glycosaminoglycan chondroitin sulfate (CS) was used; fibrillogenesis, fibril morphology, and adsorption of differently composed fibrils onto titanium were assessed. Both decorin and CS could be integrated into the fibrils during fibrillogenesis, the amount bound respectively desorbed depending on the ionic strength of fibrillogenesis buffer. Including decorin always resulted in a significant decrease of fibril diameter, CS in only a slight decrease or even increase, depending on the collagen preparation used. No significant changes in adsorption to titanium could be detected. Osteoblastic cells showed different reactions for cytoskeletal arrangement and osteopontin expression depending on the composition of the ECM, with CS enhancing the osteoblast phenotype.

A systematic review and meta-analysis on the influence of biological implant surface coatings on periimplant bone formation.

This systematic review and meta-analysis evaluated the influence of biological implant surface coatings on periimplant bone formation in comparison to an uncoated titanium reference surface in experimental large animal models. The analysis was structured according to the PRISMA criteriae. Of the1077 studies, 30 studies met the inclusion criteriae. Nineteen studies examined the bone implant contact (BIC) and were included in the meta-analysis. Overall, the mean increase in BIC for the test surfaces compared to the reference surfaces was 3.7 percentage points (pp) (95% CI -3.9-11.2, p = 0.339). Analyzing the increase in BIC for specific coated surfaces in comparison to uncoated reference surfaces, inorganic surface coatings showed a significant mean increase in BIC of 14.7 pp (95% CI 10.6-18.9, p < 0.01), extracellular matrix (ECM) surface coatings showed an increase of 10.0 pp (95% CI 4.4-15.6, p < 0.001), and peptide coatings showed a statistical trend with 7.1 pp BIC increase (95% CI -0.8-15.0, p = 0.08). In this review, no statistically significant difference could be found for growth factor surface coatings (observed difference -3.3 pp, 95% CI -16.5-9.9, p = 0.6). All analyses are exploratory in nature. The results show a statistically significant effect of inorganic and ECM coatings on periimplant bone formation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2898-2910, 2016.

Bone Formation in a Local Defect around Dental Implants Coated with Extracellular Matrix Components.

PURPOSE: The coating of implant surfaces with components of the extracellular matrix offers an approach to influence peri-implant bone healing. In this study, bone healing around coated implants is analyzed in a peri-implant defect model. MATERIALS AND METHODS: Eight months after extraction of the premolar teeth, six dogs received 48 implants (eight per animal) in the mandible. Implant surfaces were sandblasted and acid-etched, and some were additionally coated with collagen type II and chondroitin sulfate (collagen/CS). On each side of the mandible, implants either had no peri-implant defect (control side) or a vertical defect of 5 mm in depth and 0.5, 1.0, or 2.0 mm in width. Implants healed submerged for 8 weeks. Fluorochrome staining, histology, and histomorphometry were used to analyze implant osseointegration. RESULTS: Fluorochrome labels showed an increased mineralization around collagen/CS-coated surfaces at 4 weeks (p = .031). Histomorphometry generally showed lower vertical and horizontal bone apposition with increasing gap size for both surface types. In gapless sites and 0.5-mm gaps, collagen/CS coated implants showed increased bone volume in areas directly adjacent to the implant, in comparison with uncoated implants (p < .05). CONCLUSION: The width of the peri-implant gap influences peri-implant bone formation. Complete filling of all gaps by newly formed bone could not be observed around either surface. In proximity to the surface, implant surface coating by collagen/CS positively influenced bone formation.

Modification of Ti6Al4V surfaces using collagen I, III, and fibronectin. I. Biochemical and morphological characteristics of the adsorbed matrix.

Studies in developmental and cell biology have established the fact that responses of cells are influenced to a large degree by morphology and composition of the extracellular matrix. Goal of this work is to use this basic principle to improve the biological acceptance of implants by modifying the surfaces with components of the extracellular matrix (ECM). Aiming at load-bearing applications in bone contact, in this study the modification of titanium surfaces with the collagen types I and III in combination with fibronectin was undertaken; fibrillogenesis, fibril morphology and adsorption of type I, III and I/III-cofibrils onto titanium were assessed. Increasing the collagen type III amount resulted in a decrease of fibril diameter, while no significant changes in adsorption could be detected. The amount of fibronectin bound to the heterotypic fibrils depended on fibrillogenesis parameters such as ionic strength or concentration of phosphate, and varied with the percentage of integrated type III collagen.

Modification of Ti6AL4V surfaces using collagen I, III, and fibronectin. II. Influence on osteoblast responses.

Responses of osteoblastic cells are influenced by morphology and composition of the extracellular matrix, and this fact has been used to improve the biological acceptance of implants by modifying the surfaces with components of the extracellular matrix (ECM). In this study, the effect of the collagen types I and III on adhesion, proliferation, and differentiation was studied, using primary osteoblastic cells from rat calvariae. Differences in alkaline phosphatase activity (ALP) and collagen synthesis were observed between differently composed collagen coatings. An increase in collagen type III resulted in an increase in collagen synthesis and a concomitant decrease in ALP activity and Ca deposition. Initial adhesion mechanism of the cells depended on the substrate (titanium, collagen, fibronectin).

Influence of pulse ratio on codeposition of copper species with calcium phosphate coatings on titanium by means of electrochemically assisted deposition.

Aim of this study was to combine the well-known biocompatibility and ostoeconductivity of thin calcium phosphate coatings on titanium with proangiogenic signals from codeposited copper species. Copper species could be integrated in mineral layers based on hydroxyapatite by means of electrochemically assisted deposition from electrolytes containing calcium, phosphate, and copper ions. Different combinations of duration and intensity of galvanostatic pulses result in different amounts of deposited calcium phosphate and of copper species even for the same applied total charge. Absolute amounts of copper varied between 2.1 and 6.9 µg/cm², and the copper was distributed homogeneously as shown by EDX mapping. The presence of copper did not change the crystalline phase of deposited calcium phosphate (hydroxyapatite) but provoked a significant decrease in deposited amounts by factor 3 to 4. The copper was deposited mainly as Cu(I) species with a minor fraction of basic copper phosphates. Reduction of copper occurred not only at the surface of titanium but also within the hydroxyapatite coating due to the reaction with hydrogen produced by the electrolysis of water during the cathodic polarization of the substrate.