Reconstruction of calvarial bone defects using poly(amino acid)/hydroxyapatite/calcium sulfate composite

The aim of this study was to evaluate the thermal properties and in vivo interface performance of poly(amino acid) (PAA) and a composite containing PAA, hydroxyapatite (HA), and calcium sulfate (CS), with respect to their suitability for skull repair. Biocompatibility was evaluated by implantation of materials into muscles of rabbits for eight weeks. Skull repair was assessed by implanting PAA, the compact PAA/HA/CS composite (c-PAA/HA/CS), and a one-side-porous PAA/HA/CS composite (p-PAA/HA/CS) into rabbit calvarial defects. The results showed that the PAA/HA/CS composite possessed good heat resistance and possessed excellent biocompatibility and osteoconductivity. Guided bone regeneration and calvarial repair were observed, with excellent integration between calvarial tissue and implant. The p-PAA/HA/CS composite performed best in terms of stability and bone bonding between implant and host bone tissue. Thus, the present work provides new information for the potential use of osteoconductive PAA/HA/CS composites with a macrostructure in calvarial bone repair.     

A 12 month in vivo study on the response of bone to a hydroxyapatite-polymethylmethacrylate cranioplasty composite

We investigated the osteoconductivity and biocompatibility in vivo of a new hydroxyapatite-polymethylmethacrylate (HA-PMMA) composite developed for use as an implant material for cranioplasty, which is expected to have the good osteoconductivity of HA together with the strength and ease of handling of PMMA. The HA-PMMA composites were implanted in eight full-grown beagles and then 6, 12, 24 weeks and 1 year after implantation, the animals were sacrificed and the implanted materials removed along with the surrounding tissues. Extirpated specimens were studied using an optical microscope and micro-computed tomography (micro-CT). Fibrous connective tissue was prominent in the interface of the composite at 6 weeks. New bone formation was seen around the implant, 12 and 24 weeks after operation. At 1 year, new bone filled in the interface of the HA-PMMA composite and adhered to the surrounding autogenous bone. Mixing HA and PMMA did not interfere with the osteoconductivity of the HA component. In micro-CT findings, the new bone growing on the HA-PMMA composite could be seen attaching preferentially to HA particles exposed at the composite surface, rather than the PMMA. This study demonstrated that this HA-PMMA composite is a good candidate for cranial bone implants due to its good osteoconductivity and biocompatibility.     

Histomorphometric study on high-strength hydroxyapatite/poly(L-lactide) composite rods for internal fixation of bone fractures

The purpose of this study was to investigate the bone-implant interface of high-strength hydroxyapatite (HA)/poly(L-lactide) (PLLA) composite rods. As reinforcing particles, two types of HA particles-calcined HA (c-HA) and uncalcined HA (u-HA)-were applied to allow comparison of their suitability as bioactive fillers. Four types of composites (c-HA30, c-HA40, u-HA30, and u-HA40), which contained 30 or 40% by weight of each HA particle, were used. Unfilled PLLA rods were used as controls. A hole was drilled in the distal femora of 50 rabbits, and a composite or unfilled PLLA rod was implanted in a press-fit manner. Two, 4, 8, and 25 weeks after implantation, the samples were examined histologically by light microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). An image analyzer was used for histomorphometric analysis of the bone-implant interface. An affinity index was calculated for each material; this was the length of bone directly apposed to the rods expressed as a percentage of the total length of the rod surface. In all the composites, histologic examination showed new bone formation at 2 weeks after implantation. The bone gradually grew along the composite surface. SEM showed direct bone contact with the composites without intervening fibrous tissue. During follow-up, the affinity indices of all the composite rods were significantly higher than those of the unfilled PLLA rods (p < 0.01; two-way ANOVA). The maximum affinity index (41%) was attained at 4 weeks in c-HA40 rods. In contrast, little bone contact was seen in unfilled PLLA rods. The only significant difference in affinity indices among the composites was that c-HA40 had a higher affinity index than u-HA40 (p < 0.05 at 4 weeks). No disintegration of rods or polymer debris, which could elicit inflammatory tissue reactions, was observed even at 25 weeks. Our results indicate that osteoconductive bone formation on composites could enhance the stability between bone and implant in fracture repair.     

Recombinant growth/differentiation factor-5 (GDF-5) stimulates osteogenic differentiation of marrow mesenchymal stem cells in porous hydroxyapatite ceramic

To evaluate the growth/differentiation factor-5 (GDF-5) in the in vivo osteogenic potential of bone marrow mesenchymal stem cells (MSCs), we subcutaneously implanted five different kinds of hydroxyapatite (HA) ceramic implants: HA alone, GDF-5/HA composites (GDF/HA), MSCs/HA composites, the MSCs/HA composites supplemented with GDF-5 (GDF/MSCs/HA), and recombinant bone morphogenetic protein-2 (BMP/MSCs/HA). Neither the HA alone nor the GDF/HA composites exhibited any bone formation at any time after implantation. At 4 weeks, the MSCs/HA composites exhibited a certain amount of bone formation in some pore areas. In contrast, at 2 weeks, the GDF/MSCs/HA composites exhibited histologically obvious de novo bone formation together with active osteoblasts in many pore areas and additional bone formation at 4 weeks. In the de novo formed bone, neither chondrocytes nor endochondral bone was detected. The GDF/MSCs/HA composites also showed high alkaline phosphatase (ALP) and osteocalcin expression determined at both the protein and gene levels and the high level of expression was well maintained even at 4 weeks. Compared with GDF/MSCs/HA, the BMP/MSCs/HA composites exhibited excellent osteogenesis with relatively early osteoblastic phenotype expression. The results indicate that GDF-5 synergistically enhances de novo bone formation capability of MSCs/HA composite and suggest that tissue-engineered GDF/MSCs/HA composites could be used as bone graft substitutes.     

Evaluation of biomechanical strength,stability, bioactivity,and in vivo biocompatibility of a novel calcium deficient hydroxyapatite/poly(amino acid) composite cervical vertebra cage

A new type of cervical vertebra cage was prepared using a novel composite, calcium deficient hydroxyapatite/poly(amino acid) (HA/PAA), and its mechanical properties, in vitro stability and bioactivity, and in vivo biocompatibility were characterized. The results showed that the axial compressive loads of the HA/PAA cage were in the range of 10058–10612 N and the lateral compressive loads were in the range of 1180–2363 N, and varied with the height of the cervical vertebra cages. After immersion in simulated body fluid (SBF) for 16 weeks, the axial compressive loads of the cage decreased from 10058 to 7131 N and the lateral compressive loads decreased from 1180 to 479 N. In addition, the weight loss decreased 6.01%, showing that HA/PAA composites had good stability during the incubation period. The pH value of SBF was also monitored during the whole soaking period; it fluctuated in the range of 6.9–7.4. Scanning electron microscope and energy dispersive spectrometer results showed the cage was bioactive with a new apatite layer attached on the surface. The histological evaluation revealed that new bone tissue bonded tightly with the surfaces of the implants, showing excellent biocompatibility. In conclusion, the HA/PAA cage showed sufficient strength, good stability, bioactivity, and biocompatibility, and has potential applications for clinical cervical vertebrae repair.     

HA/PDLLA复合材料的体内成骨过程研究

目的研究HA／PDLLA复合材料植入体内后与细胞、组织的相互作用，探讨HA／PDLLA复合材料在体内的成骨过程，为其临床应用及设计具有生物功能的人工骨替换材料和骨组织工程支架材料提供依据。方法采用液相吸附法制备了HA／PDLLA复合材料，以纯PDLLA和空白组进行对照，进行体内植入实验，通过组织学观察和四环素标记考察其成骨过程。结果HA／PDLLA复合材料植入机体后，体内的无菌性炎症轻微，新骨形成速率高于PDLLA材料。HA微粒的存在，加强了复合材料的机械强度，使之可以避免过早的丧失力学强度。第24w时，材料被组织分隔包裹，新生骨组织长入材料，骨愈合情况良好。结论HA／PDLLA复合材料具有良好的生物相容性、生物降解性能、生物学活性和骨传导性能。     

Comparison of plasma-sprayed hydroxyapatite coatings and zirconia-reinforced hydroxyapatite composite coatings: in vivo study

The clinical use of plasma-sprayed hydroxyapatite (HA) coatings on metal implants has been widely adopted because the HA coating can achieve the firmly and directly biological fixation with the surrounding bone tissue. However, the long-term mechanical properties of HA coatings has been concern for the long-term clinical application. Previous research showed that the concept of adding ZrO2 as second phase to HA significantly increased the bonding strength of plasma-sprayed composite material. The present work aimed to explore the biological properties, including the histological responses and shear strength, between the plasma-sprayed HA and HA/ZrO2 coating, using the transcortical implant model in the femora of canines. After 6 and 12 weeks of implantation, the HA coating revealed the direct bone-to-coating contact by the backscattered electron images (BEIs) of scanning electron microscope (SEM), but the osseointegration was not observed at the surface of HA/ZrO2 coating. For new bone healing index (NBHI) and apposition index (AI), the values for HA implants were significantly higher than that for HA/ZrO2 coatings throughout all implant periods. After push-out test, the shear strength of HA-coated implants were statistically higher than HA/ZrO2 coated implants at 6- and 12-week implantation, and the failure mode of HA/ZrO2 coating was observed at the coating-bone interface by SEM. The results indicate that the firm fixation between bone and HA/ZrO2 has not been achieved even after 12-week implantation. Consequently, the addition of ZrO2 could improve the mechanical properties of coatings, while the biocompatibility was influenced by the different material characteristics of HA/ZrO2 coating compared to HA coatings.     

In vivo bone tissue response to a canasite glass-ceramic

The aim of this study was to determine the biocompatibility and osteoconductive potential of a high-strength canasite glass ceramic. Glass-ceramic rods were produced using the lost-wax casting technique and implanted in the mid-shafts rabbit femurs. Implants were harvested at 4, 13 and 22 weeks and prepared for light and electron microscopy. Hydroxyapatite was used as a control material. Hydroxyapatite implants were surrounded by new mineralised bone tissue after 4 weeks of implantation. The amount of bone surrounding the implant increased slightly at 13 weeks. In contrast, canasite glass and glass ceramic implants were almost entirely surrounded by soft tissue during all the time periods. Close contact between bone and canasite glass-ceramic implant without the intervening fibrous tissue was observed in only a few regions. The canasite formulation evaluated was not osteoconductive and appeared to degrade in the biological environment. It was therefore concluded that the canasite formulation used was unsuitable for use as implant. Further work is required to improve the biocompatibility of these materials with bone tissue. It is possible that this could be achieved by reducing the solubility of the glass and glass ceramic.     

Hydroxyapatite-based composite for dental implants: an in vivo removal torque experiment

Screw-shaped dental implants were fabricated from commercially pure Ti (c.p. Ti) and HA-based composites. The HA-based composites were fabricated by mixing HA with Al(2)O(3)-coated ZrO(2) powders. The mechanical properties of these composites were enhanced by a factor of 3. These were implanted into the rabbit tibiae and the removal torque to loosen the implants in vivo was measured in order to investigate the osteointegration. After a healing period of 6 weeks, the implants were retrieved with a torque gauge instrument. The HA-based composite implants showed an almost 2-times-higher removal torque when compared to the Ti implants (ANOVA, p < 0.05), indicating excellent biocompatibility to bone. Thus, HA-based composites had not only better mechanical properties but also similar bioactivity as HA itself. It is believed that a HA-based composite is suitable for artificial dental implants.     

Push-out testing and histological evaluation of glass reinforced hydroxyapatite composites implanted in the tibia of rabbits.

In vitro and in vivo bioactivity studies were performed to assess the biocompatibility of CaO-P2O5 glass-reinforced hydroxyapatite (GR-HA) composites. The ability to form an apatite layer by soaking in simulated body fluid (SBF) was examined and surfaces were characterized using FTIR reflection and thin-film X-ray diffraction analyses. Qualitative histology, histomorphometric measurements, and push-out testing were performed in a rabbit model for characterizing bone/implant bonding. Under the in vitro conditions using SBF, an apatite layer could not be formed on GR-HA composites within 8 weeks. Results of push-out testing showed bonding between the composites and bone, ranging from 130-145 N after 2 weeks of implantation. After the longest implantation period, 16 weeks, the GR-HA composite prepared with the higher content of CaO-P2O5 glass showed the highest bonding force, 606 +/- 45 N, compared to 459 +/- 30 N for sintered HA. Development of immature bone and modifications in the turnover of a more mature bone on the surface of GR-HA composites were similar to those on sintered HA.     

聚DL-乳酸/羟基磷灰石复合材料修复长骨缺损的实验研究

目的 :评价羟基磷灰石 (HA)复合聚DL 乳酸 (PDLLA )制备的材料体内成骨能力。方法 :将PDLLA和PDLLA/HA( 2 0wt % )材料采用盐结晶颗粒沥滤法制成三维多孔材料 ,45例 1cm兔桡骨去骨膜缺损分为三组 ,分别植入 2种材料和作空白对照 ,术后 2 ,4,8,12周行X线、组织学及扫描电镜观察骨生成状况 ,8、12周行生物力学测试 (三点折弯强度 )。结果 :泡沫状PDLLA/HA ( 2 0wt % )材料比纯PDLLA成骨更好 (P <0 .0 5 ) ,实验组与对照组相比差异有显著性 (P <0 .0 5 )。结论 :PDLLA具有良好的生物相容性 ,制成多孔状具有较好的骨传导性能 ,HA( 2 0wt % )的加入促进了多孔PDLLA的骨传导能力 ,提高了骨生成的质量。PDLLA/HA( 2 0wt % )复合材料是一种有临床应用前景的骨移植材料。     

In vitro osteoblastic response to 30 vol% hydroxyapatite-polyethylene composite

Hydroxyapatite-reinforced high-density polyethylene (HA-HDPE) composite, as a bone replacement material, has successfully been used clinically as middle ear prostheses and orbital floor implants. The aim of this study was to examine its in vitro biocompatibility in order to develop a further application, that is, as skull reconstruction implants. Human osteoblast cells isolated from femoral heads and crania were used to determine the biological response of the composites. HA-HDPE composites (30 vol %) with two grades of HA filler that had different surface morphologies were selected for this in vitro assessment. The results showed that HA-HDPE composite was bioactive and supported osteoblast attachment, proliferation, and differentiation. The composite with rough-surfaced HA filler demonstrated slightly better cellular response than the composite with smooth-surfaced HA filler. Although osteoblastic cells derived from skull showed an overall slower response compared with those from femoral heads, these in vitro results show that HA-HDPE composite potentially could be used as a skull implant.     

Bioactivity and osseointegration study of calcium phosphate ceramic of different chemical composition

Synthetic hydroxyapatite (HA) and tricalcium phosphate (TCP) are promising bone-substitute materials in the orthopaedic and dental fields, as their chemical composition is similar to that of bone. This study investigated the osseointegration performance of carbonated biphasic calcium phosphate (CBCP) ceramics containing carbonated hydroxyapatite and tricalcium phosphate prepared by microwave irradiation, in femoral defects of dogs. The defects were created as 3-mm holes on the lateral aspect of femur and filled with the implant material. The serum was collected postoperatively and biochemical assays for alkaline phosphatase activity levels were carried out. The animals' defective sites were radiographed at 4, 8, and 12 weeks. The radiographic results showed that the process of ossification started after 4 weeks and the defect was completely filled with new bone after 8 weeks. Histological examination of the tissue showed the osteoblastic activity inducing the osteogenesis in the defect. The complete haversian system with osteoblastic and osteoclastic activity and bone remodelling process were observed after 12 weeks. The alkaline phosphatase activity levels also correlated with the formation of osteoblast cells. This calcium phosphate ceramic has proved to work well as a biocompatible implant and as an osteoconductive and osteoinductive material for the filling of bone defects.     

Comparison of new bone formation, implant integration, and biocompatibility between RGD-hydroxyapatite and pure hydroxyapatite coating for cementless joint prostheses--an experimental study in rabbits

This is the first work to report on additional Arginin-Glycin-Aspartat (RGD) coating on precoated hydroxyapatite (HA) surfaces regarding new bone formation, implant bone contact, and biocompatibility compared to pure HA coating and uncoated stainless K-wires. There were 39 rabbits in total with 6 animals for the RGD-HA and HA group for the 4 week time period and 9 animals for each of the 3 implant groups for the 12 week observation. A 2.0 K-wire either with RGD-HA or with pure HA coating or uncoated was placed into the intramedullary canal of the tibia. After 4 and 12 weeks, the tibiae were harvested and three different areas of the tibia were assessed for quantitative and qualitative histology for new bone formation, direct implant bone contact, and formation of multinucleated giant cells. Both RGD-HA and pure HA coating showed statistically higher new bone formation and implant bone contact after 12 weeks than the uncoated K-wire. There were no significant differences between the RGD-HA and the pure HA coating in new bone formation and direct implant bone contact after 4 and 12 weeks. The number of multinucleated giant did not differ significantly between the RGD-HA and HA group after both time points. Overall, no significant effects of an additional RGD coating on HA surfaces were detected in this model after 12 weeks.     

In vivo evaluation of a porous hydroxyapatite/poly-DL-lactide composite for use as a bone substitute

We investigated the biocompatibility, osteoconductivity, and biodegradability of a porous composite of hydroxyapatite (HA) and poly-DL-lactide (PDLLA) implanted into rabbit femoral condyles and compared it with porous HA. Six weeks after implantation, the HA/PDLLA was covered with bone and contacted the bone directly. The amount of newly formed bone in the pores was similar in both materials during the examined period. The newly formed bone in the HA/PDLLA tended to increase over 26 weeks, but that in the HA did not show a significant increase after 12 weeks. By 26 weeks, remodeling of the newly formed bone in the pores was seen and bone marrow tissue was found in the pores of the HA/PDLLA. The porous HA/PDLLA was resorbed much faster than the porous HA. Porous HA/PDLLA was resorbed continuously through bone formation and remodeling. Conversely, porous HA was scarcely resorbed throughout the period. HA/PDLLA is thought to be degraded almost completely after about 1 year, and in this study, porous HA/PDLLA showed excellent osteoconductivity and faster resorption than HA. Therefore, HA/PDLLA might be a desirable material for bone substitutes.     

In vivo evaluation of a novel porous hydroxyapatite to sustain osteogenesis of transplanted bone marrow-derived osteoblastic cells

Biosynthetic bone grafts are considered to contain one or more of three critical components: osteoprogenitor cells, an osteoconductive matrix, and osteoinductive growth factors. The basic requirements of the scaffold material are biocompatibility, mechanical integrity, and osteoconductivity. A major design problem is satisfying these requirements with a single composite. In this study, we hypothesize that one composite that combines bone marrow-derived osteoblasts and a novel mechanical reinforced porous hydroxyapatite with good biocompatibility and osteoconductivity (HA/BMO) can reach these requirements. A novel sintered porous hydroxyapatite (HA) was prepared by the following procedures. The HA slurry was foamed by adding polyoxyethylenelaurylether (PEI) and mixing. The pores were fixed by crosslinking PEI with diepoxy compounds and the HA porous body was sintered at 1200 degrees C for 3 h. The HA sintered porous body had a high porosity (77%), and was completely interconnected. Average pore diameter was 500 microm and the interconnecting path 200 microm in diameter. The compressive (17 MPa) and three-point bending (7 MPa) strengths were high. For in vivo testing, the 2-week subcultured HA/BMO (+) composites were implanted into subcutaneous sites of syngeneic rats until 8 weeks after implantation. These implants were harvested at different time points and prepared for the biochemical analysis of alkaline phosphatase activity (ALP) and bone osteocalcin content (OCN), and histological analysis. ALP and OCN in the HA/BMO group were much higher than those in the HA without BMOs control group 1 week after implantation (p < 0.001). Light microscopy revealed mature bone formation in the HA/BMO composite 4 weeks after implantation. In the SEM study, mineralized collagenous extracellular matrix was noted in HA/BMO composite 2 weeks after implantation with numbers of active osteoblasts. We conclude that the composite of the novel HA and cultured BMOs has osteogenic ability in vivo. These results provide a basis for further studies on the use of this composite as an implant in orthopaedic surgery.     

In vitro and in vivo behaviour of Ca- and P-enriched anodized titanium.

The influence of different surface preparations on titanium biocompatibility and bone integration was evaluated. Commercially grade 2 titanium rods (diameter 2 mm, length: 3 mm), vacuum annealed and hydrofluoric acid etched was selected for its promising surface characteristics to achieve good direct osseointegration. Some rods were surface modified by Anodic Spark Discharge anodization and a thin layer (approximately 5 microm) of amorphous TiO2 containing Ca and P (Ti/AM) was obtained. Some of the Ti/AM specimens underwent a further hydrothermal treatment to produce a thin outermost layer (approximately 1 microm) of hydroxyapatite (Ti/AM/HA). Cytotoxicity tests (direct contact: ISO 10993-5) showed good cytocompatibility for all tested samples. Ti and tissue culture substrate + DMEM control, respectively, were associated with a significant higher proportion of attached cells than Ti/AM and Ti/AM/HA (P < 0.0005), but this was in the normal range of 10-20% of unattached cells for cytocompatible materials. Histomorphometric analysis conducted on samples inserted in the cancellous bone of distal femoral epiphysis of Sprague-Dawley rats gave the following results at 4 and 8 weeks: Affinity index (AI%) data proving the surface osteconductive properties of non-anodized acid etched Ti (AI-4 weeks: 67.1 +/- 17.0%; AI-8 weeks: 74.8 +/- 11.5%). Ti/AM samples showed the lowest values (AI-4 weeks: 45.8 +/- 15.9%; AI-8 weeks: 68.5 +/- 13.6%) while the best performances of the Ti/AM/HA samples (AI-4 weeks: 60.4 +/- 21.8%; AI-8 weeks: 79.5 + 9.37%) indicated that hydroxyapatite allowed a higher bone to implant contact respect to Ti only. Further investigations should be performed in order to better understand the mechanism of observed in vitro behaviour and to achieve information on long-term osseointegration process.     

Histological evaluation and surface componential analysis of modified micro-arc oxidation-treated titanium implants

The objective of this study is to investigate soft tissue and bone tissue reaction to titanium implants treated by a modified micro arc oxidation (MAO) technique, and analyze the surface components and implant-bone contact ratio by animal experiments to evaluate the osseointegration condition of implants with this modified MAO surface. MAO titanium plates were installed subcutaneously in rabbits. Tissue reaction was evaluated by HE sections. MAO titanium implants designed for endosseous examination were installed in Beagles' femurs. Bone tissue surrounding implants was analyzed histologically. Surfaces of retrieved implants were observed and examined by SEM and EDX. All procedures were performed under the control of untreated pure titanium implants. Thin homogeneous fibrous envelope could be found without apparent inflammation cells infiltration around the subcutaneously imbedded MAO titanium plates, which was almost same as control group. Fast osteoid deposition comprising high content of calcium, phosphor, carbon, and nitrogen elements was found on the retrieved MAO implant surfaces, while comparatively less amount of carbon and nitrogen elements were found on the retrieved implants of control group. Matured bone tissue comprising bone trabeculae and Haversian canals appeared in 8 weeks, while it took 12 weeks needed to form matured bone tissue in control group. In conclusion, MAO titanium materials shows good biocompatibility and calcium phosphate inducement capability in vivo and could accelerate bone tissue growth and shorten the osseointegration time.     

In vivo study on biocompatibility and bonding strength of hydroxyapatite-20vol%Ti composite with bone tissues in the rabbit

Biocompatibility and bonding strength of hydroxyapatite-20vol%Ti composite fabricated by hot-pressing technique with bone tissues in the rabbit were investigated by in vivo studies in comparison with those of Ti metal and dense HA ceramic. Although fibrous tissues formed at the interface between the composite and bone tissues at 3 weeks in vivo, bonding strength of the composite increases faster than that of dense HA after 4 weeks. At 3 months in vivo, bonding strength of the composite is higher than that of dense HA and exceeds 6.5 MPa. Moreover, as compared with the visible bonding interfaces between dense HA and new bones, the bonding interfaces for the composite cannot already be distinguished and the composite was osseointegrated fully with bone tissues into one bony body. The shear fracture of bonding strength test for the composite occurred in new bone zones near the interface, which indicates that bonding strength of the composite could even exceed the shear strength of new bones after 3 months in vivo. In conclusion, HA-Ti composite has better osteoconduction and osseointegration abilities than Ti metal and dense HA ceramic after 3 months in vivo and is a promising biomaterial for hard tissue replacement.     

Osteopontin functionalization of hydroxyapatite nanoparticles in a PDLLA matrix promotes bone formation

We studied the osteoconductive tissue response of hydroxyapatite (HA) nanoparticles functionalized with osteopontin (OPN) in a matrix of poly-D,L-lactic-acid (PDLLA). In a canine endosseus 0.75-mm gap implant model, we tested the osteointegrative impact of the OPN functionalized composite as an implant coating, and a non-functionalized composite was used as reference control. During the four weeks of observation, the OPN functionalized composite coating significantly increased the formation of new bone in the porosities of the implant, but no differences were observed in the gap. The study provides evidence of its potential use either alone or in combination with other osteoconductive compounds.