In vivo study of the effect of RGD treatment on bone ongrowth on press-fit titanium alloy implants

Early bone ongrowth is known to increase primary implant fixation and reduce the risk of early implant failure. Arg-Gly-Asp (RGD) peptide has been identified as playing a key role in osteoblast adhesion and proliferation on various surfaces. The aim for this study is to evaluate the effect of RGD peptide coating on the bony fixation of orthopaedic implants, to justify its further evaluation in clinical applications. Sixteen unloaded cylindrical plasma sprayed Ti6Al4V implants coated with cyclic RGD peptide were inserted as press-fit in the proximal tibia of 8 mongrel dogs for 4 weeks. Uncoated control implants were inserted in the contralateral tibia. Results were evaluated by histomorphometry and mechanical push-out test. A significant two-fold increase was observed in bone ongrowth for RGD-coated implants. Also, fibrous tissue ongrowth was significantly reduced for RGD-coated implants. Bone volume was significantly increased in a 0-100 microm zone around the implant. The increased bony anchorage resulted in moderate increases in mechanical fixation as apparent shear stiffness was significantly higher for RGD-coated implants. Increases in median ultimate shear strength and energy to failure were also observed. This study demonstrates that cyclic RGD coating increases early bony fixation of unloaded press-fit titanium implants.     

Differential effect of a bone morphogenetic protein-7 (OP-1) on primary and revision loaded, stable implants with allograft

Morselized impacted bone allograft is often used to reconstruct the bone bed in the revision of failed total joint arthroplasties. We hypothesized that addition of the bone morphogenetic protein OP-1 (BMP-7) to bone allograft would improve early implant fixation. We inserted one loaded 6-mm-diameter titanium implant (surrounded by 0.75-mm gap) in each medial condyle of 24 canines. On one side, the implant was inserted in a controlled experimental revision setting resembling the clinical revision situation. A primary implant was inserted on the contralateral side in a previously unoperated site. Three groups were studied: 1) allograft alone, 2) allograft + 0.4 mg OP-1, and 3) allograft + 0.8 mg OP-1. Implant fixation was evaluated at 4 weeks. Grafted implants inserted in the primary setting without OP-1 had better fixation than the grafted revision setting with or without OP-1 (significantly more bone coverage, more mineralized tissue in the gap, and better mechanical interface strength). However, grafted primary implants with OP-1 had impaired fixation compared with grafted primary implants without OP-1 (less bone coverage of the implant and less bone formation in the gap). In contrast, grafted revision implants with OP-1 significantly increased implant fixation compared with grafted revision implants without OP-1 (increased mechanical interface strength and fraction of mineralized tissue in the gap). We found no differences between the two doses in any of the settings. Addition of OP-1 to bone allografted implants may show benefit at sites with impaired bone healing capacities, such as the revision setting.     

In vivo evaluation of bone-bonding ability of RGD-coated porous implant using layer-by-layer electrostatic self-assembly

RGD has been demonstrated to improve implant osseointegration. However, few studies are known about an effect of RGD coating on a bone-bonding ability of screw-shaped porous implant. The aim of this study was to investigate the effect of RGD coating using the layer-by-layer self-assembly technique on the bone-bonding ability of porous implant. 60 implants of 10 mm in length (30 control and 30 RGD-coated) were inserted into femurs of 30 rabbits and 30 implants of 8 mm in length (15 control and 15 RGD-coated) were inserted into tibias of 15 rabbits. At 4, 8, and 12 weeks post-implantation, femurs and tibias were retrieved and prepared for removal torque tests (RTQ) and histomorphometric evaluation, respectively. No differences were found in the RTQ values between two implants at 4 weeks (p = 0.932). There were statistical significances in the RTQ values at 8 and 12 weeks (p = 0.002, 0.001, respectively). New bone was formed on both implant surfaces. The bone-implant contact pattern appeared to produce a broad-based direct contact in both implants. The RGD-coated implants showed a significantly greater BIC in the threads inside the cortical bone compared with the control implants at 4, 8, and 12 weeks (p = 0.024, 0.041, 0.022, respectively). No differences were found in the bone area within the same threads between two implants at 4 weeks (p = 0.806) whereas differences were found at 8 and 12 weeks (p = 0.009, 0.031, respectively). It was concluded that RGD coating using the layer-by-layer self-assembly technique has a positive effect on the bone-bonding ability of porous implant.     

Osteogenic protein-1 enhances osseointegration of titanium implants coated with peri-apatite in rabbit femoral defect

This study evaluated the effect of osteogenic protein-1 (OP-1) carried by Peri-Apatite (PA) on bone healing in the gap surrounding implants in a rabbit model. Cylindrical titanium implants (3 x 9 mm) were uniformly coated with PA precipitated from a calcium and phosphate solution. OP-1 solution containing 60 microg OP-1 was directly loaded on the implants immediately before implantation for the experimental group, whereas buffer solution was loaded on the implants for the control. The implant was placed in the distal femur and surrounded by a 1-mm gap. The implants were retrieved and examined 6 weeks after implantation. Mechanical testing (push-out) data showed that OP-1 enhanced implant fixation by 80%. Histomorphometric measurements indicated that bone ingrowth in the initial gap expressed as a percentage of the whole gap was significantly higher in the specimens treated with OP-1 than the control group (25.4% vs. 8.9%, p < 0.05). The percentage of the surface of implants, which was covered by bone, was significantly higher in the OP-1-treated group compared to the control group (65% vs. 25%, p < 0.05). This study suggests that OP-1 can be loaded on orthopedic implants through PA to enhance the osseointegration of orthopedic implant.     

Loading improves anchorage of hydroxyapatite implants more than titanium implants

Roentgen Stereophotogrammetric Analysis (RSA) studies have shown that the quality of the early fixation of implants has a dominant effect on their long-term function. To evaluate methods to improve their fixation, we examined the influence of mechanical loading and surface coating on the quality of the bone-implant interface. We compared the fixation of a cylindrical, stable 6.0 mm implant initially surrounded by a 0.75 mm concentric gap, after 4 weeks of loaded or unloaded conditions. Two types of surfaces were analyzed: plasma sprayed hydroxyapatite (HA) and plasma sprayed titanium (Ti). The histomorphometric evaluation showed that HA implants had greater bone coverage than Ti implants, and this coverage was further increased under loaded conditions only for HA. Furthermore, loading reduced the fibrous tissue coverage for the HA implants, while it increased fibrous tissue coverage for Ti implants. These findings were in agreement with pushout results showing that HA implants had greater shear strength, stiffness, and energy than Ti implants, and (except for energy) these parameters were further increased under loaded conditions only for HA. In addition, because the two implant surfaces exhibited a different relative response to load, it is important to evaluate new surfaces under the more clinically relevant loaded condition.     

Bone compaction enhances fixation of hydroxyapatite-coated implants in a canine gap model

Primary cementless joint replacement depends partly on the ability of bone to heal into those areas of an inserted implant where a gap to surrounding bone initially exists. A new bone preparation technique, compaction, has enhanced gap-healing around grit-blasted implants without osteo-conductive properties. However, hydroxyapatite (HA) porous-coated implants with osteo-conductive properties are often inserted clinically to enhance gap healing and implant fixation. It is unknown whether the osteo-conductive properties of HA porous-coated implants might overwhelm the beneficial effects of compaction on gap healing. Therefore, we compared the compaction technique with the conventional bone-removing technique, drilling, using HA porous-coated implants in a canine gap model. HA porous-coated titanium implants were bilaterally inserted into oversized cavities of the proximal humeri of seven dogs. Each dog served as its own control. Thus, one humerus had the implant cavity prepared with compaction, the other with drilling. Two weeks after surgery push-out test and histomorphometry was performed. Compaction significantly increased ultimate shear strength, energy absorption, apparent shear stiffness, bone implant contact, and peri-implant bone density. The results of this study suggest that compaction may enhance gap healing when osteo-conductive HA porous coated implants are inserted in joint replacements.     

Bone healing of commercial oral implants with RGD immobilization through electrodeposited poly(ethylene glycol) in rabbit cancellous bone

Immobilization of RGD peptides on titanium (Ti) surfaces enhances implant bone healing by promoting early osteoblastic cell attachment and subsequent differentiation by facilitating integrin binding. Our previous studies have demonstrated the efficacy of RGD peptide immobilization on Ti surfaces through the electrodeposition of poly(ethylene glycol) (PEG) (RGD/PEG/Ti), which exhibited good chemical stability and bonding. The RGD/PEG/Ti surface promoted differentiation and mineralization of pre-osteoblasts. This study investigated the in vivo bone healing capacity of the RGD/PEG/Ti surface for biomedical application as a more osteoconductive implant surface in dentistry. The RGD/PEG/Ti surface was produced on an osteoconductive implant surface, i.e. the grit blasted micro-rough surface of a commercial oral implant. The osteoconductivity of the RGD/PEG/Ti surface was compared by histomorphometric evaluation with an RGD peptide-coated surface obtained by simple adsorption in rabbit cancellous bone after 2 and 4 weeks healing. The RGD/PEG/Ti implants displayed a high degree of direct bone apposition in cancellous bone and achieved greater active bone apposition, even in areas of poor surrounding bone. Significant increases in the bone to implant contact percentage were observed for RGD/PEG/Ti implants compared with RGD-coated Ti implants obtained by simple adsorption both after 2 and 4 weeks healing (P<0.05). These results demonstrate that RGD peptide immobilization on a Ti surface through electrodeposited PEG may be an effective method for enhancing bone healing with commercial micro-rough surface oral implants in cancellous bone by achieving rapid bone apposition on the implant surface.     

No effect of hydroxyapatite particles in phagocytosable sizes on implant fixation: an experimental study in dogs

The influence of wear debris on bone healing around orthopedic implants is debated. Hydroxyapatite (HA) particles and polyethylene (PE) particles have been shown to have a negative effect on osteoblast cultures in vitro. The present study investigated the in vivo effects of HA and PE particles on the mechanical fixation and gap healing around experimental HA implants. Nonloaded implants (n = 30) were inserted bilaterally into the proximal tibia of 15 dogs with a 2-mm gap to the bone. The peri-implant gap was either (1) empty (n = 6) or filled with (2) hyaluronic acid (n = 8), (3) hyaluronic acid and HA particles (n = 8), or (4) hyaluronic acid and PE particles (n = 8). After 4 weeks, the animals were killed. The implant interface was evaluated by pushout testing until failure and by histomorphometry. Both HA and PE particles were found to be phagocytosed by macrophage-like cells in the interfacial tissue. HA particles were also integrated in newly formed bone. We found no negative effect of the particulate material on mechanical fixation of the implants or on bone formation around the implants.     

A novel surface treatment for porous metallic implants that improves the rate of bony ongrowth

Rapid implant fixation could prove beneficial in a host of clinical applications from total joint arthroplasty to trauma. We hypothesized that a novel self-assembled monolayer of phosphonate molecules (SAMP) covalently bonded to the oxide surface of titanium alloy would enhance bony integration. Beaded metallic rods were treated with one of three coatings: SAMP, SAMP + RGD peptide, or hydroxyapatite. Rods were inserted retrogradely into both distal femurs of 60 rabbits. Fifteen rabbits were sacrificed at 2, 4, 8, and 16 weeks. At each time, seven specimens for mechanical pull-out testing and three for histomorphometric analysis were available for each coating. At four weeks, both SAMP groups had significantly higher failure loads when compared to hydroxyapatite (p < 0.01). No significant differences were found among groups at other times, though the SAMP-alone group remained stronger at 16 weeks. Histology showed abundant new bone formation around all the three groups, though more enhanced formation was apparent in the two SAMP groups. With this novel treatment, with or without RGD, the failure load of implants doubled in half the time as compared with hydroxyapatite. Where early implant fixation is important, the SAMP treatment provides a simple, cost-effective enhancement to bony integration of orthopaedic implants.     

The effect of integrin-specific bioactive coatings on tissue healing and implant osseointegration

Implant osseointegration, defined as bone apposition and functional fixation, is a requisite for clinical success in orthopaedic and dental applications, many of which are restricted by implant loosening. Modification of implants to present bioactive motifs such as the RGD cell-adhesive sequence from fibronectin (FN) represents a promising approach in regenerative medicine. However, these biomimetic strategies have yielded only marginal enhancements in tissue healing in vivo. In this study, clinical-grade titanium implants were grafted with a non-fouling oligo(ethylene glycol)-substituted polymer coating functionalized with controlled densities of ligands of varying specificity for target integrin receptors. Biomaterials presenting the alpha5beta1-integrin-specific FN fragment FNIII 7-10 enhanced osteoblastic differentiation in bone marrow stromal cells compared to unmodified titanium and RGD-presenting surfaces. Importantly, FNIII 7-10-functionalized titanium significantly improved functional implant osseointegration compared to RGD-functionalized and unmodified titanium in vivo. This study demonstrates that bioactive coatings that promote integrin binding specificity regulate marrow-derived progenitor osteoblastic differentiation and enhance healing responses and functional integration of biomedical implants. This work identifies an innovative strategy for the rational design of biomaterials for regenerative medicine.     

Coralline hydroxyapatite granules inferior to morselized allograft around uncemented porous Ti implants: unchanged fixation by addition of concentrated autologous bone marrow aspirate

We compared early fixation of titanium implants grafted with impacted allograft bone or coralline hydroxyapatite (HA) granules (Pro Osteon 200) with and without the addition of concentrated bone marrow cells (BMC). Autologous bone marrow aspirate was centrifuged to increase the BMC concentration. Four nonloaded cylindrical, porous coated titanium implants with a circumferential gap of 2.3 mm were inserted in the proximal humeri of eight dogs. Coralline HA granules +/- BMC were impacted around the two implants on one side, and allograft +/- BMC was impacted around the contra lateral implants. Observation time was 4 weeks. The implants surrounded by allograft bone had a three-fold better fixation than the HA-grafted implants. The concentration of BMC after centrifugation was increased with a factor 2.1. The addition of BMC to either of the bone graft materials had no statistically significant effects on implant fixation. The allografted implants were well osseointegrated, whereas the HA-grafted implants were largely encapsulated in fibrous tissue. The addition of concentrated autologous BMCs to the graft material had no effect on implant fixation. The HA-grafted implants were poorly anchored compared with allografted implants, suggesting that coralline HA granules should be considered a bone graft extender rather than a bone graft substitute.     

Histological analysis of bone/heteroplastic implant interfaces in dog tibia.

This work presents histological analysis of interfaces between bone and heteroplastic implants in dog tibias. The study was performed in four tibias (of four mongrel dogs) into which cylindrical implants were inserted. One ceramic (titania) implant and three grit-blasted titanium implants (with sandblasted and acid-corroded surfaces) were chosen for histological analysis of the implant surface/bone tissue interface. The implants remained in the tibias for eight months and none were loaded during this period. The animals were subsequently sacrificed and the samples were processed for analysis. Light microscope analysis revealed a large amount of osteoid tissue and proximity of osteoblasts and osteocytes to the implant surfaces. In addition, little or no fibrous tissue was observed between the bone and implant surfaces. The titanium implants presented better osseointegration than did the ceramic implant.     

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.     

Effect of osteogenic protein 1/collagen composite combined with impacted allograft around hydroxyapatite-coated titanium alloy implants is moderate.

This study evaluated the effects of osteogenic protein 1/collagen composite (OP-1/col) mixed with impacted allograft around hydroxyapatite (HA)-coated titanium alloy implants in a canine model. The aim of the study was to test different doses of OP-1 growth factor in a collagen composite for stimulatory effect on allograft incorporation around an implant. Unloaded implants were inserted in each proximal humerus of 16 skeletally mature dogs. The cylindrical implants (4 x 9 mm) coated with HA were initially surrounded by a 3-mm gap into which allograft mixed with OP-1/col was impacted. Two different doses of OP-1 were investigated. In eight animals 325 mg OP-1 protein and 130 mg bovine collagen type I as carrier were mixed with the allograft chips.This composite is identical to the clinically used OP-1 device called Novus. In another eight animals a lower dose of 65 mg OP-1 protein and 130 mg bovine collagen type I was used. Control implants placed in the contralateral humerus were surrounded by allograft mixed with collagen carrier only. The dogs were euthanized at 6 weeks. Implant fixation was determined by push-out testing. Bone ingrowth and bone formation were evaluated by quantitative histomorphometry on serial sections of the bone-implant interface. Impacted allograft together with low-dose OP-1 enhanced bone volume in a zone adjacent to HA-coated titanium alloy implants. The high dose had no effect on bone formation. Mechanical fixation, bone ingrowth, and bone volume in the gap near the original trabecular bone were unaffected by both low and high OP-1/col composite. In this model and observation period, the low dose of OP-1/col composite mixed with impacted allograft has a moderate effect on bone healing around HA-coated implants and no effect on implant fixation.     

Use of injectable calcium-phosphate cement for the fixation of titanium implants: an experimental study in goats

This in vivo study evaluated the fixation of two types of titanium implants with the use of an injectable calcium-phosphate (CaP) cement. The cement was either used to create a cement mantle (Type A implant) or as an additive to press-fit placed titanium plasma sprayed implants (Type B implant). The implants were placed in trabecular bone of the medial femoral condyle of goats and left in place for 2 and 10 weeks. Mechanical evaluation of the implant fixation was done by torque testing. This showed that for the Type A implants the calcium-phosphate cement's performance was significantly inferior (P < 0.05) to that of polymethylmethacrylate cement fixation. For the two-week Type B implants a significant increase (P < 0.05) in failure load was found for calcium-phosphate cemented implants compared with just press-fitted Type B implants. Histological evaluation revealed that for Type A implants, failure during torque testing occurred at the implant-cement interface. In contrast, for Type B implants, failure occurred in the bone-implant interface for press-fit-placed devices and in the cement layer for CaP-cemented devices. Further, the CaP cement was found to be overgrown with new formed bone already after 2 weeks of implantation. The cement showed resorption due to regular bone remodeling. On the basis of these observations, it was concluded that the use of injectable CaP cement might facilitate earlier loading of press-fit inserted titanium implants. Nevertheless, the results have to be confirmed in dynamical mechanical as well as loaded in vivo studies.     

Bone growth enhancement in vivo on press-fit titanium alloy implants with acid etched microtexture

Early bone ongrowth secures long-term fixation of primary implants inserted without cement. Implant surfaces roughened with a texture on the micrometer scale are known to be osseoconductive. The aim of this study was to evaluate the bone formation at the surface of acid etched implants modified on the micro-scale. We compared implants with a nonparticulate texture made by chemical milling (hydrofluoric acid, nitric acid) (control) with implants that had a dual acid etched (hydrofluoric acid, hydrochloric acid) microtexture surface superimposed on the primary chemically milled texture. We used an experimental joint replacement model with cylindrical titanium implants (Ti-6Al-4V) inserted paired and press-fit in cancellous tibia metaphyseal bone of eight canines for 4 weeks and evaluated by histomorphometric quantification. A significant twofold median increase was seen for bone ongrowth on the acid etched surface [median, 36.1% (interquartile range, 24.3-44.6%)] compared to the control [18.4% (15.6-20.4%)]. The percentage of fibrous tissue at the implant surface and adjacent bone was significantly less for dual acid textured implants compared with control implants. These results show that secondary roughening of titanium alloy implant surface by dual acid etching increases bone formation at the implant bone interface.     

Ultrastructural comparisons of ceramic and titanium dental implants in vivo: a scanning electron microscopic study

Identically prepared, screw-type ceramic and titanium endosteal dental implants were inserted in the jaws of adult mongrel dogs for periods of up to 6 months. Sixteen of the 32 total implants supported fixed bridgework. The interface of bone and soft connective tissues with the dental implants was examined by routine and innovative scanning electron microscopic (SEM) techniques using both secondary and backscattered electron imaging. Results demonstrated excellent bone adaptation to both titanium and ceramic implants. Direct adaptation of bone to the upper third of both type implants was observed with only minimal amounts of any intervening fibrous connective tissue. A composite of trabecular bone and fibrous connective tissue was observed in the lower two-thirds of the implants examined. Areas of bone alteration suggestive of osteoid were observed at the thread apicis of some loaded implants. From this investigation we concluded that similar longitudinal tissue responses were generated to one-piece, cylindrical screw-type titanium and alpha alumina oxide ceramic dental implants. Possible bone remodeling was observed at the thread apicis of the loaded implants, an area where occlusal forces may be distributed. We further suggest that one-stage endosteal implants are capable of maintaining a proportional bone-to-implant interface at the apical support region, similar to that suggested to two-stage implant systems.     

Titanium metals form direct bonding to bone after alkali and heat treatments

In this article we evaluated the bone-bonding strengths of titanium and titanium alloy implants with and without alkali and heat treatments using the conventional canine femur push-out model. Four kinds of smooth cylindrical implants, made of pure titanium or three titanium alloys, were prepared with and without alkali and heat treatments. The implants were inserted hemitranscortically into canine femora. The bone-bonding shear strengths of the implants were measured using push-out test. At 4 weeks all types of the alkali- and heat-treated implants showed significantly higher bonding strength (2.4-4.5 MPa) than their untreated counterparts (0.3-0.6 MPa). At 12 weeks the bonding strengths of the treated implants showed no further increase, while those of the untreated implants had increased to 0.6-1.2MPa. Histologically, alkali- and heat-treated implants showed direct bonding to bony tissue without intervening fibrous tissue. On the other hand, untreated implants usually had intervening fibrous tissue at the interface between bone and the implant. The early and strong bonding to bone of alkali- and heat-treated titanium and its alloys without intervening fibrous tissue may be useful in establishing cementless stable fixation of orthopedic implants.     

The effect of adding an equine bone matrix protein lyophilisate on fixation and osseointegration of HA-coated Ti implants

Joint replacements should be firmly anchored in vital bone to avoid early implant subsidence and late aseptic loosening. We investigated whether the fixation of orthopedic implants could be improved by adding an osteoinductive extract of lyophilized equine bone matrix proteins (Colloss E, Ossacur AG, Germany), between the implant and the surrounding bone. Eighteen uncemented HA-coated implants were inserted pairwise in the proximal tibia of nine dogs. All implants were surrounded by a 2 mm concentric defect. In each dog, the intervention implant was added 20 mg protein lyophilisate. The contralateral control implant was inserted untreated. After four weeks, the treated HA-coated implants had better mechanical fixation than the untreated control implants. The treated implants were better osseointegrated, there was more newly formed bone around these implants, and fibrous tissue was eliminated. The mechanical implant fixation had a strong positive correlation to new bone formation on and around the implant, and a strong negative correlation to fibrous tissue encapsulation. The results suggest that bone protein extracts such as the Colloss E device may augment early implant fixation of even HA-coated Ti implants and thereby reduce the risk of long-term failure. This may be particularly useful in revision arthroplasty with bone loss.     

A new electrochemically graded hydroxyapatite coating for osteosynthetic implants promotes implant osteointegration in a rat model

Hydroxyapatite (HAP) is widely used as an osteoconductive coating for orthopedic implants. So far standard coating methods like plasma spraying produce a relatively thick coating layer (>30 microm). In addition, the chemical structure of the HAP may be altered because of the heating throughout the coating process. This may have negative effects on the coating stability, implant fixation, and induction of bone formation. The relatively thick layer may detach from the implant with the risk of wear debris. In the present study the potential of a newly developed HAP coating of implants on osteointegration was investigated in a rat model. The coating method, based on an electrochemical process, is applied in a graded manner and results in a biodegradable HAP coating with a thickness of approximately 2 mum. Coated versus uncoated titanium Kirschner wires (1.4-mm diameter) were inserted into the medullary cavity of the right femora of 5-month old female Sprague Dawley rats (n=36) in a retrograde fashion. Throughout an experimental period of 2 months the osteointegration was traced radiologically. After this time the animals were sacrificed and the implant integration was tested biomechanically with the use of a push-out test. To analyze the bone-implant interface, histological sections (80 mum) were investigated with an image analyzing system. The biomechanical testing revealed a significantly higher implant fixation in the group treated with the HAP-coated implant (shear strength: 27.8 +/- 6.7 MPa) compared to control (shear strength: 8.08 +/- 3.4 MPa). The histological analyses demonstrated a better ingrowth of the implants in the HAP group with significantly more direct bone-implant contacts compared to the control group. The results demonstrate that the HAP coating promotes implant osteointegration in a rat model.