Bone formation at recombinant human bone morphogenetic protein-2-coated titanium implants in the posterior mandible (Type II bone) in dogs

Background: Conventional oral/maxillofacial implants reach osseointegration over several months during which the titanium fixtures interact with alveolar bone. The objective of this study was to determine if adsorbing recombinant human bone morphogenetic protein‐2 (rhBMP‐2) onto a titanium porous oxide (TPO) implant surface might enhance or accelerate local bone formation and support osseointegration in a large animal oral/maxillofacial orthotopic model. Material and Methods: Endosseous implants with a TPO surface were installed into the edentulated posterior mandible in eight adult Hound Labrador mongrel dogs. The implant surface had been adsorbed with rhBMP‐2 at 0.2 or 4.0 mg/ml. TPO implants without rhBMP‐2 served as control. Treatments were randomized between jaw quadrants. Mucosal flaps were advanced and sutured leaving the implants submerged. Clinical and radiographic evaluations were made immediately post‐surgery, at day 10 (suture removal), and week 4 and 8 post‐surgery. The animals received fluorescent bone markers at week 3, 4, and at week 8 post‐surgery, when they were euthanized for histologic analysis. Results: TPO implants coated with rhBMP‐2 exhibited dose‐dependent bone remodelling including immediate resorption and formation of implant adjacent bone, and early establishment of clinically relevant osseointegration. The resulting bone–implant contact, although clinically respectable, appeared significantly lower for rhBMP‐2‐coated implants compared with the control [rhBMP‐2 (0.2 mg/ml) 43.3±10.8%versus 71.7±7.8%, p<0.02; rhBMP‐2 (4.0 mg/ml) 35.4±10.6%versus 68.2±11.0%, p<0.03]. Conclusions: rhBMP‐2 adsorbed onto TPO implant surfaces initiates dose‐dependent peri‐implant bone re‐modelling resulting in the formation of normal, physiologic bone and clinically relevant osseointegration within 8 weeks.     

Bone formation at recombinant human bone morphogenetic protein-2-coated titanium implants in the posterior maxilla (Type IV bone) in non-human primates

Background: Studies using ectopic rodent and orthotopic canine models (Type II bone) have shown that titanium porous oxide (TPO) surface implants adsorbed with recombinant human bone morphogenetic protein‐2 (rhBMP‐2) induce local bone formation including osseointegration. The objective of this study was to evaluate local bone formation and osseointegration at such implants placed into Type IV bone. Material and Methods: rhBMP‐2‐coated implants were installed into the edentulated posterior maxilla in eight young adult Cynomolgus monkeys: four animals each received three TPO implants adsorbed with rhBMP‐2 (2.0 mg/ml) and four animals each received three TPO implants adsorbed with rhBMP‐2 (0.2 mg/ml). Contra‐lateral jaw quadrants received three TPO implants without rhBMP‐2 (control). Treatments were alternated between left and right jaw quadrants. Mucosal flaps were advanced and sutured to submerge the implants. The animals received fluorescent bone markers at weeks 2, 3, 4, and at week 16 when they were euthanized for histologic analysis. Results: Clinical healing was uneventful. Extensive local bone formation was observed in animals receiving implants adsorbed with rhBMP‐2 (2.0 mg/ml). The newly formed bone exhibited a specific pinpoint bone–implant contact pattern regardless of rhBMP‐2 concentration resulting in significant osseointegration; rhBMP‐2 (2.0 mg/ml): 43% and rhBMP‐2 (0.2 mg/ml): 37%. Control implants exhibited a thin layer of bone covering a relatively larger portion of the implant threads. Thus, TPO control implants bone exhibited significantly greater bone–implant contact (～75%; p<0.05). There were no statistically significant differences between rhBMP‐2‐coated and control implants relative to any other parameter including peri‐implant and intra‐thread bone density. Conclusion: rhBMP‐2‐coated TPO implants enhanced/accelerated local bone formation in Type IV bone in a dose‐dependent fashion in non‐human primates resulting in significant osseointegration. rhBMP‐2‐induced de novo bone formation did not reach the level of osseointegration observed in native resident bone within the 16‐week interval.     

Alveolar ridge augmentation using implants coated with recombinant human bone morphogenetic protein-2: radiographic observations

Objectives: Effective carrier technologies and dosing appear critical for the successful use of bone morphogenetic proteins (BMPs). This study evaluated radiographically the potential of a purpose‐designed titanium porous‐oxide implant surface combined with recombinant human BMP‐2 (rhBMP‐2) to stimulate alveolar ridge augmentation. Material and methods: Twelve young‐adult Labrador dogs were used. Three 10‐mm titanium implants per jaw quadrant were placed 5 mm into the alveolar ridge following extraction of the premolar teeth and reduction of alveolar ridge. Six animals received implants coated with rhBMP‐2 at 0.75 or 1.5 mg/ml randomized to contralateral jaw quadrants. Another six animals received implants coated with rhBMP‐2 at 3 mg/ml or uncoated control using the same split‐mouth design. The mucoperiosteal flaps were advanced, adapted, and sutured to submerge the implants. Radiographic registrations were made immediately postsurgery (baseline), and at weeks 4 and 8 (end of study). Results: rhBMP‐2‐coated implants exhibited robust radiographic bone formation extending to and above the implant platform from week 4 (P<0.01). Some rhBMP‐2‐coated implants showed voids within the newly formed bone that gradually resolved and/or implant displacement, being severe in two animals receiving implants coated with rhBMP‐2 at 3 mg/ml. Controls showed limited, if any, new bone formation at weeks 4 and 8 postsurgery. There were no significant differences among the rhBMP‐2 groups in bone gain. Conclusions: The titanium porous‐oxide surface serves as an effective carrier for rhBMP‐2, showing a clinically significant potential to stimulate local bone formation. With the carrier technology used, therapeutic dosage appears to be in the range of 0.75–1.5 mg/ml.     

Alveolar ridge augmentation using implants coated with recombinant human bone morphogenetic protein-7 (rhBMP-7/rhOP-1): radiographic observations

Aim: The objective of this study was to radiographically evaluate the potential of a purpose‐designed titanium porous‐oxide implant surface coated with recombinant human bone morphogenetic protein‐7 (rhBMP‐7), also known as recombinant human osteogenic protein‐1 (rhOP‐1), to stimulate alveolar ridge augmentation. Material and Methods: Six young‐adult Hound Labrador mongrel dogs were used. Three 10 mm titanium oral implants per jaw quadrant were placed 5 mm into the alveolar ridge in the posterior mandible following surgical extraction of the pre‐molar teeth and reduction of the alveolar ridge leaving 5 mm of the implants in a supra‐alveolar position. The implants had been coated with rhBMP‐7 at 1.5 or 3.0 mg/ml and were randomized to contralateral jaw quadrants using a split‐mouth design. The mucoperiosteal flaps were advanced, adapted, and sutured to submerge the implants. Radiographic registrations were made immediately post‐surgery (baseline), and at weeks 4 and 8 (end of study). Results: rhBMP‐7‐coated implants exhibited robust radiographic bone formation. At 8 weeks, bone formation averaged 4.4 and 4.2 mm for implants coated with rhBMP‐7 at 1.5 and 3.0 mg/ml, respectively. There were no significant differences between the rhBMP‐7 concentrations at any observation interval. A majority of the implant sites showed voids within the newly formed bone at week 4 that generally resolved by week 8. The newly formed bone assumed characteristics of the resident bone. Conclusions: The titanium porous‐oxide implant surface serves as an effective carrier for rhBMP‐7 showing a clinically significant potential to stimulate local bone formation.     

RhBMP-2/alphaBSM induces significant vertical alveolar ridge augmentation and dental implant osseointegration

Background: Recombinant human bone morphogenetic protein 2 (rhBMP‐2) in a carrier has been shown to induce significant bone formation. Several candidate carriers, however, lack structural integrity to offset compressive forces that may compromise rhBMP‐2 bone induction, in particular, for challenging onlay indications such as alveolar ridge augmentation. Purpose: The objective of this study was to evaluate rhBMP‐2 in a calcium‐phosphate cement carrier, αBSM, for vertical alveolar ridge augmentation and immediate dental implant Osseointegration. Materials and Methods: Six adult Hound Labrador mongrels with 5 mm critical size supra‐alveolar peri‐implant defects were used. Three animals received rhBMP‐2/αBSM (rhBMP‐2 at 0.40 and 0.75 mg/mL) in contralateral jaw quadrants (total implant volume/defect ～ 1.5 mL). Three animals received αBSM without rhBMP‐2 (control group). The animals were euthanized at 16 weeks post surgery, and block biopsies were processed for histologie and histometric analysis. Results: rhBMP‐2/αBSM induced substantial augmentation of the alveolar ridge. Control sites exhibited limited new bone formation. Vertical bone augmentation averaged (SD) 4.9 ± 1.0 mm (rhBMP‐2 at 0.40 mg/mL), 5.3 ± 0.3 mm (rhBMP‐2 at 0.75 mg/mL), and 0.4 ± 0.4 mm (control); new bone area 8.5 ± 4.2 mm ², 9.0 ± 1.9 mm ², and 0.5 ± 0.4 mm ²; new bone density 55.1 ± 6.4%, 61.1 ± 6.0%, and 67.7 ± 9.5%; and new bone‐implant contact 26.9 ± 17.5%, 28.5 ± 1.4%, and 24.6 ± 16.1%, respectively. Residual αBSM comprised 1% of the new bone. Bone density for the contiguous resident bone ranged from 65 to 71%, and bone‐implant contact ranged from 49 to 64%. Conclusions: Surgical implantation of rhBMP‐2/αBSM appears an effective protocol for vertical alveolar ridge augmentation procedures and immediate dental implant Osseointegration and for onlay indications of lesser complexity.     

Comparative Study of Chinese Hamster Ovary Cell Versus Escherichia coli‐Derived Bone Morphogenetic Protein‐2 Using the Critical‐Size Supraalveolar Peri‐Implant Defect Model

Background: Chinese hamster ovary (CHO) cell‐derived recombinant human bone morphogenetic protein‐2 (rhBMP‐2) has been introduced for spine, long bone, and craniofacial indications. Escherichia coli‐ (E. coli) derived rhBMP‐2 displays comparable efficacy to CHO cell‐derived rhBMP‐2 in vitro and in small‐animal models. The objective of this study is to evaluate the efficacy of E. coli‐derived rhBMP‐2 compared to the benchmark CHO cell‐derived rhBMP‐2 using an established large‐animal model. Methods: Contralateral, critical‐size supraalveolar peri‐implant defects in six adult male Hound Labrador mongrel dogs received CHO cell‐ or E. coli‐derived rhBMP‐2 (0.2 mg/mL) in an absorbable collagen sponge (ACS) carrier. In each quadrant, three dental implants were placed. A titanium mesh device was used to support space provision. The animals received fluorescent bone markers for qualitative evaluations. Animals were euthanized at 8 weeks for histopathologic and histometric evaluation. Results: Clinical healing included significant swelling, but none of the animals experienced wound dehiscences. CHO cell‐ and E. coli‐derived rhBMP‐2 supported comparable bone formation (new bone area, 35.8 ± 3.6 versus 30.1 ± 2.2 mm²; bone density, 31.8% ± 1.6% versus 35.6% ± 2.5%; and osseointegration, 32.9% ± 7.4% versus 33.7% ± 8.1%) without statistically significant differences between treatments. Newly formed immature delicate trabecular bone in fibrovascular marrow filled the space underneath the titanium mesh and extended coronally above the mesh. Seroma formation was frequently observed. There were no discernable qualitative histologic differences between treatments. Conclusion: CHO cell‐ and E. coli‐derived rhBMP‐2 in an ACS carrier appear equally effective at inducing local bone formation in support of dental implant osseointegration.     

Space-providing expanded polytetrafluoroethylene devices define alveolar augmentation at dental implants induced by recombinant human bone morphogenetic protein 2 in an absorbable collagen sponge carrier

Background: Surgical implantation of recombinant human bone morphogenetic protein 2 (rhBMP‐2) in an absorbable collagen sponge carrier (ACS) significantly enhances bone regeneration in horizontal alveolar defects; however, sufficient quantities of bone for implant dentistry are not routinely obtained. Purpose: The objective of this proof‐of‐principle study was to evaluate the potential of a space‐providing macroporous expanded polytetrafluoroethylene (ePTFE) device to control volume and geometry of rhBMP‐2/ACS‐induced alveolar bone augmentation. Materials and Methods: Bilateral critical‐size supra‐alveolar periimplant defects were created in four Hound‐Labrador mongrel dogs. Two turned and one surface‐etched 10 mm titanium dental implants were placed 5 mm into the surgically reduced alveolar ridge creating 5 mm supra‐alveolar defects. rhBMP‐2/ACS (0.4 mg rhBMP‐2) was placed around the exposed dental implants. Additionally, one jaw quadrant in each animal was randomly assigned to receive the domeshaped macroporous ePTFE device. Mucoperiosteal flaps were advanced for primary wound closure. The animals were euthanized at 8 weeks post surgery for histometric analysis. Results: The space‐providing macroporous ePTFE device defined the volume and geometry of rhBMP‐2/ACS‐induced bone formation, whereas bone formation at sites receiving rhBMP‐2/ACS alone varied considerably. Vertical bone gain at turned dental implants averaged (SD) 4.7 ± 0.2 mm at sites receiving rhBMP‐2/ACS and the ePTFE device compared with 3.5 ± 0.9 mm at sites receiving rhBMP‐2/ACS only. The corresponding values for rhBMP‐2/ACS‐induced bone area were 9.6 ± 0.7 mm ² and 7.5 ± 6.2 mm ². There was a highly significant correlation between induced bone area and the space provided by the ePTFE device (p .001). There was no difference in induced bone density or bone‐implant contact between the two technologies. These observations were consistent with those observed at surface‐etched dental implants. Conclusions: The data from this study suggest that a space‐providing macroporous ePTFE device defines rhBMP‐2/ACS‐induced alveolar augmentation to provide adequate bone quantities for implant dentistry. The dental implant surface technology does not appear to substantially influence bone formation.     

Histological and biomechanical evaluation of phosphorylcholine-coated titanium implants

Objective: Compounds considered for drug delivery from oral implant surfaces in support of local bone formation might themselves influence osseointegration. Phosphorylcholine (PC) polymers have been shown to enhance the biocompatibility of medical devices and to serve as drug delivery systems. The objective of this study was to evaluate local bone formation and osseointegration at PC and positively charged PC (PC+)‐coated endosseous implants in an established rabbit model. Material and Methods: Sixteen adult female New Zealand White rabbits were used. Eight animals received PC‐coated and control titanium porous oxide surface implants placed in the left and right distal femural condyle (trabecular bone) and proximal tibial metaphysis (cortical bone) using aseptic routines. The remaining eight animals similarly received PC+ and control implants. One implant was placed in each femural condyle and two implants in each tibial metaphysis. Experimental and control implants were alternated between the left and right hind legs. Fascia and skin were closed in layers. The animals were euthanized following a 6‐week healing interval for biomechanical (removal torque) and histometric analyses. Results: Peri‐implant bone density was considerably greater at tibial compared with femoral sites within as well as immediately outside the implant threads. However, there were no significant differences in bone density among PC, PC+, and control implants. Nevertheless, bone–implant contact was significantly lower at PC compared with PC+ and control implants in cortical bone (p<0.05). Numerical differences in trabecular bone did not reach statistical significance. The removal torque evaluation revealed significantly lower values for PC compared with PC+ and control sites (p<0.05). Conclusion: The histometric and biomechanical analyses suggest that PC coating may influence biological processes and ultimately osseointegration of endosseous implants. Apparently, incorporation of cationic charges may reverse or compensate for this scenario. Nevertheless, both PC coatings exhibited clinically acceptable osseointegration. In perspective, PC technology appears to be a viable candidate delivery system for agents in support of local bone formation at endosseous implant surfaces.     

Histomorphometric analysis of the osseointegration of four different implant surfaces in the femoral epiphyses of rabbits

Objectives: The surface properties of titanium dental implants are key parameters for rapid and intimate bone–implant contact. The osseointegration of four implant surfaces was studied in the femoral epiphyses of rabbits. Material and methods: Titanium implants were either grit‐blasted with alumina or biphasic calcium phosphate (BCP) ceramic particles, coated with a thin octacalcium phosphate (OCP) layer, or prepared by large‐grit sand blasting and acid‐etched (SLA). After 2 and 8 weeks of implantation, the bone‐implant contact and bone growth inside the chambers were compared. Scanning electron microscopy (SEM) and profilometry showed distinct microtopographies. Results: The alumina‐Ti, BCP‐Ti and OCP‐Ti groups had similar average surface roughness in the 1–2 μm range whereas the SLA surface was significantly higher with a roughness averaging 4.5 μm. Concerning the osseointegration, the study demonstrated a significantly greater bone‐to‐implant contact for both the SLA and OCP‐Ti surfaces as compared with the grit‐blasted surfaces, alumina‐ and BCP‐Ti at both 2 and 8 weeks of healing. Conclusion: In this animal model, a biomimetic calcium phosphate coating gave similar osseointegration to the SLA surface. This biomimetic coating method may enhance the apposition of bone onto titanium dental implants.     

Oral implants placed in bone defects treated with Bio‐Oss®, Ostim®‐Paste or PerioGlas: an experimental study in the rabbit tibiae

Objectives: To compare the histological features of bone filled with Bio‐Oss^®, Ostim‐Paste^® or PerioGlas placed in defects in the rabbit tibiae by evaluating bone tissue composition and the integration of titanium implants placed in the grafted bone. Material and methods: Two cylindrical bone defects, about 4 mm in diameter and 6 mm in depth, were created in the tibiae of 10 rabbits. The defects were filled with either Bio‐Oss^®, PerioGlas, Ostim^®‐Paste or left untreated, and covered with a collagen membrane. Six weeks later, one titanium sandblasted and acid‐etched (SLA) implant was inserted at the centre of each previously created defect. The animals were sacrificed after 6 weeks of healing. Results: Implants placed in bone previously grafted with Bio‐Oss^®, PerioGlas or Ostim^®‐Paste obtained a larger extent of osseointegration, although not statistically significant, than implants placed in non‐grafted bone. The three grafting materials seemed to perform in a similar way concerning their contribution towards implant osseointegration. All grafting materials appeared to be osteoconductive, thus leading to the formation of bridges of mineralized bone extending from the cortical plate towards the implants surface through the graft scaffold. Conclusions: Grafting with the above‐mentioned biomaterials did not add any advantage to the osseointegration of titanium SLA implants in a self‐contained defect.     

The effect of combined delivery of recombinant human bone morphogenetic protein-2 and recombinant human vascular endothelial growth factor 165 from biomimetic calcium-phosphate-coated implants on osseointegration

Objectives: The delivery of growth factors for enhanced osseointegration depends on the effectiveness of the carrier systems at the bone–implant interface. This study evaluated the effect of solo and dual delivery of recombinant human bone morphogenetic protein‐2 (rhBMP‐2) and recombinant human vascular endothelial growth factor (rhVEGF₁₆₅) from biomimetically octacalcium phosphate‐coated implants on osseointegration. Materials and methods: Biomimetic implants, bearing either a single growth factor (BMP or VEGF) or their combination (BMP+VEGF), were established, and compared with acid‐etched (AE, control) and biomimetic implants without growth factor (CAP). Implants were placed into frontal skulls of nine domestic pigs. The quality of osseointegration was evaluated using microradiographic and histomorphometric analysis of bone formation inside four defined bone chambers of the experimental implant at 1, 2 and 4 weeks. Results: Biomimetic implants, either with or without growth factor, showed enhanced bone volume density (BVD) values after 2 and 4 weeks. This enhancement was significant for the BMP and BMP+VEGF group compared with the control AE group after 2 weeks (P<0.05). All biomimetic calcium‐phosphate (Ca‐P) coatings exhibited significantly enhanced bone–implant contact (BIC) rates compared with the uncoated control surface after 2 weeks (P<0.05). However, the combined delivery of BMP‐2 and VEGF did not significantly enhance BIC at the final observation period. Conclusion: It was concluded that the combined delivery of BMP‐2 and VEGF enhances BVD around implants, but not BIC. Therefore, it may be assumed that changes in the surface characteristics should be considered when designing growth factor‐delivering surfaces. To cite this article:
Ramazanoglu M, Lutz R, Ergun C, von Wilmowsky C, Nkenke E, Schlegel K A. The effect of combined delivery of recombinant human bone morphogenetic protein‐2 and recombinant human vascular endothelial growth factor 165 from biomimetic calcium‐phosphatecoated implants on osseointegration.
Clin. Oral Impl. Res. xx , 2011; 000–000.
doi: 10.1111/j.1600‐0501.2010.02133.x     

Osseointegration of commercial microstructured titanium implants incorporating magnesium: a histomorphometric study in rabbit cancellous bone

Objective: Recent studies have suggested that magnesium (Mg) ions exert a beneficial effect on implant osseointegration. This study assessed the osseointegration of nanoporous titanium (Ti) surface incorporating the Mg produced by hydrothermal treatment in rabbit cancellous bone to determine whether this surface would further enhance bone healing of moderately rough‐surfaced implants in cancellous bone, and compared the result with commercially available micro‐arc oxidized Mg‐incorporated implants. Material and methods: The Mg‐incorporated Ti surfaces (RBM/Mg) were obtained by hydrothermal treatment using an alkaline Mg‐containing solution on grit‐blasted moderately rough (RBM) implants. Untreated RBM and recently introduced Mg‐incorporated microporous Ti implants produced by micro‐arc oxidation (M) were used controls in this study. The surface characteristics were evaluated by scanning electron microscopy, X‐ray photoelectron spectroscopy and optical profilometry. Twenty‐four threaded implants with a length of 10 mm (eight RBM implants, eight RBM/Mg implants and eight M implants) were placed in the femoral condyles of 12 New Zealand White rabbits. Histomorphometric analysis was performed 4 weeks after implantation. Results: Hydrothermally treated and untreated grit‐blasted implants displayed almost identical surface morphologies and R_a values at the micron‐scale. The RBM/Mg implants exhibited morphological differences compared with the RBM implants at the nano‐scale, which displayed nanoporous surface structures. The Mg‐incorporated implants (RBM/Mg and M) exhibited more continuous bone apposition and a higher degree of bone‐to‐implant contact (BIC) than the untreated RBM implants in rabbit cancellous bone. The RBM/Mg implants displayed significantly greater BIC% than untreated RBM implants, both in terms of the all threads region and the total lateral length of implants (P<0.05), but no statistical differences were found between the RBM/Mg and M implants except BIC% values in total lateral length. Conclusion: These results indicate that a nanoporous Mg‐incorporated surface may be effective in enhancing the osseointegration of moderately rough grit‐blasted implants by increasing the degree of bone?implant contact in areas of cancellous bone. To cite this article :
Park J‐W, An C‐H, Jeong S‐H, Suh J‐Y. Osseointegration of commercial microstructured titanium implants incorporating magnesium: a histomorphometric study in rabbit cancellous bone.
Clin. Oral Impl. Res. 23 , 2012; 294–300.
doi: 10.1111/j.1600‐0501.2010.02144.x     

Tissue integration of a new titanium-zirconium dental implant: a comparative histologic and radiographic study in the canine

Background: This study evaluates a newly developed titanium–zirconium implant (TiZr), comparing it to a commercially available pure titanium (Ti) implant subjected to the same surface treatment. Methods: In nine dogs, 12 implants (six TiZr and six Ti) were randomly placed in the mandible with the implant shoulder at the bone crest and subjected to submerged healing. Standardized radiographs were taken after implantation, and at the sacrifice of 2 weeks (three dogs), 4 weeks (three dogs), and 8 weeks (three dogs). Histologic and histomorphometric measurements were performed on non‐decalcified histologic sections. The main outcome measures included the first bone–implant contact (fBIC) and BIC over time. For statistical analysis, Wilcoxon signed‐rank test and mixed model regressions were applied. Results: From baseline to 8 weeks, a mean bone loss of 0.09 ± 0.33 mm for TiZr and a gain of 0.02 ± 0.33 mm for Ti were calculated radiographically. The number of implants with the fBIC coronal to the reference point (implant shoulder) gradually increased over time, reaching 39% of all TiZr implants and 50% of all Ti implants at 8 weeks. The mean fBIC values for Ti and TiZr were 0.29 ± 0.42 mm and 0.26 ± 0.32 mm (2 weeks), ?0.01 ± 0.20 mm and 0.10 ± 0.28 mm (4 weeks), and ?0.06 ± 0.22 mm and 0.08 ± 0.30 mm (8 weeks), respectively. The mean BIC values peaked at 86.9% ± 6.8% (8 weeks) for TiZr and at 83.4% ± 5.9% (4 weeks) for Ti. No statistically significant differences were observed at any time point. Conclusion: TiZr and Ti bone level implants with chemically‐modified, sandblasted, and acid‐etched surfaces performed similarly in regards to osseointegration in this unloaded canine study.     

Effects of Simvastatin on bone healing around titanium implants in osteoporotic rats

Objectives: Osteoporosis is known to impair the process of implant osseointegration. The recent discovery that statins (HMG‐CoA reductase inhibitors) act as bone anabolic agents suggests that statins can be used as potential agents in the treatment of osteoporosis. Therefore, we hypothesized that statins will promote osteogenesis around titanium implants in subjects with osteoporosis. Material and methods: Fifty‐four female Sprague Dawley rats, aged 3 months old, were randomly divided into three groups: Sham‐operated group (SHAM; n=18), ovariectomized group (OVX; n=18), and ovariectomized with Simvastatin treatment group (OVX+SIM; n=18). Fifty‐six days after being ovariectomized (OVX), screw‐shaped titanium implants were inserted into the tibiae. Simvastatin was administered orally at 5 mg/kg each day after the placement of the implant in the OVX+SIM group. The animals were sacrificed at either 28 or 84 days after implantation and the undecalcified tissue sections were obtained. Bone‐to‐implant contact (BIC) and bone area (BA) within the limits of implant threads were measured around the cortical (zone A) and cancellous (zone B) bone regions. Furthermore, bone density (BD) of zone B in a 500 μm wide zone lateral to the implants was also measured. Results: There were no significant differences in BIC and BA measurements in zone A in any of the three groups at either 28 or 84 days after implantation (P>0.05). By contrast, in zone B, significant differences in the measurement of BIC, BA, and BD were observed at 28 and 84 days between all three groups. Bone healing decreased with lower BIC, BA, and BD around implant in OVX group compared with other two groups, and Simvastatin reversed the negative effect of OVX on bone healing around implants with the improvement of BIC, BA, and BD in zone B. Conclusion: Osteoporosis can significantly influence bone healing in the cancellous bone around titanium implants and Simvastatin was shown to significantly improve the osseointegration of pure titanium implants in osteoporotic rats.     

Influence of two barrier membranes on staged guided bone regeneration and osseointegration of titanium implants in dogs. Part 2: augmentation using bone graft substitutes

Objectives: To assess the influence of two barrier membranes and two bone graft substitutes on staged guided bone regeneration and osseointegration of titanium implants in dogs. Materials and methods: Saddle‐type defects were prepared in the lower jaws of 6 fox hounds and randomly filled with a natural bone mineral (NBM) and a biphasic calcium phosphate (SBC) and allocated to either an in situ gelling polyethylene glycol (PEG) or a collagen membrane (CM). At 8 weeks, modSLA titanium implants were inserted and left to heal in a submerged position. At 8+2 weeks, respectively, dissected blocks were processed for histomorphometrical analysis (e.g., mineralized tissue [MT], bone‐to‐implant contact [BIC]). Results: The mean MT values (mm²) and BIC values (%) tended to be higher in the PEG groups (MT: NBM [3.4±1.7]; SBC [4.2±2]/BIC: NBM [67.7±16.9]; SBC [66.9±17.8]) when compared with the corresponding CM groups (MT: NBM [2.5±0.8]; SBC [2.3±1.6]/BIC: NBM [54.1±22.6]; SBC [61±8.7]). These differences, however, did not reach statistical significance. Conclusion: It was concluded that all augmentation procedures investigated supported bone regeneration and staged osseointegration of modSLA titanium implants. To cite this article :
Mihatovic I, Becker J, Golubovic V, Hegewald A, Schwarz F. Influence of two barrier membranes on staged guided bone regeneration and osseointegration of titanium implants in dogs. Part 2: augmentation using bone graft substitutes.
Clin Oral Impl Res. 23 , 2012; 308–315.
doi: 10.1111/j.1600‐0501.2011.02238.x     

Biofunctionalization of titanium implants with a biomimetic active peptide (P‐15) promotes early osseointegration

Objectives: The early stages of peri‐implant bone formation play an essential role in the osseointegration and long‐term success of dental implants. By incorporating bioactive coatings, this biofunctionalization of implant surfaces may enhance the attachment of the implant to the surrounding bone and stimulate bone regeneration. Material and methods: To demonstrate faster osseointegration, the surfaces of dental implants were grit‐blasted and acid‐etched. They were then coated with hydroxyapatite (HA) and experimental implants were further coated with a biomimetic active peptide (P‐15) in one of two concentrations. These biofunctionalized samples and controls with no peptide were placed in the forehead region of 12 adult pigs. Six animals were evaluated for a period of 14 or 30 days. Results: Histomorphometric analysis demonstrated that the implants with the high concentration of P‐15 had significantly higher percentage of bone‐to‐implant contact (BIC) at 14 (P=0.018) and 30 (P=0.015) days compared with the other groups. Both concentrations of P‐15 showed increased peri‐implant bone density compared to the control group at 30 days. Conclusion: Biofunctionalization of the implant surface with a biomimetic active peptide leads to significantly increased BIC rates at 14 and 30 days and higher peri‐implant bone density at 30 days. To cite this article:
Lutz R, Srour S, Nonhoff J, Weisel T, Damien CJ, Schlegel KA. Biofunctionalization of titanium implants with a biomimetic active peptide (P‐15) promotes early osseointegration.
Clin. Oral Impl. Res. 21 , 2010; 726–734.
doi: 10.1111/j.1600‐0501.2009.01904.x     

Effects of anodized implants coated with Escherichia coli-derived rhBMP-2 in beagle dogs

This study evaluated the effects of Escherichia coli-derived rhBMP-2 (ErhBMP-2) coated onto anodized implants to stimulate bone formation, osseointegration and vertical bone growth in a vertical bone defect model. Six young adult beagle dogs were used. After a 2-month bone healing period, anodized titanium implants (8 mm in length) were placed 5.5 mm into the mandibular alveolar ridge. Eighteen implants coated with ErhBMP-2 (BMP group) and another 18 uncoated implants (control group) were installed using a randomized split-mouth design. The implant stability quotient (ISQ) values were measured. Specimens were fabricated for histometric analysis to evaluate osseointegration and bone formation. The ISQ values at 8 weeks after implant placement were significantly higher in the BMP group than in the control group (p < 0.05). Histological observations showed that the changes in bucco-lingual alveolar bone levels were higher in the BMP group than in the control group (p < 0.05). The ErhBMP-2 coated anodized implants can stimulate bone formation and increase implant stability significantly on completely healed alveolar ridges in dogs. Further studies evaluating the effects of ErhBMP-2 on osseointegration in the bone–implant interface are warranted.     

Osseointegration of one‐piece zirconia implants compared with a titanium implant of identical design: a histomorphometric study in the dog

Objective: The aim of this study was to evaluate osseointegration of one‐piece zirconia vs. titanium implants depending on their insertion depth by histomorphometry. Material and methods: Four one‐piece implants of identical geometry were inserted on each side of six mongrel dogs: (1) an uncoated zirconia implant, (2) a zirconia implant coated with a calcium‐liberating titanium oxide coating, (3) a titanium implant and (4) an experimental implant made of a synthetic material (polyetheretherketone). In a split‐mouth manner they were inserted in submerged and non‐submerged gingival healing modes. After 4 months, dissected blocks were stained with toluidine blue in order to histologically assess the bone‐to‐implant contact (BIC) rates and the bone levels (BL) of the implants. Results: All 48 implants were osseointegrated clinically and histologically. Histomorphometrically, BL in the crestal implant part did not differ significantly with regard to material type or healing modality. The submerged coated zirconia implants tended to offer the most stable crestal BL. The histometric results reflected the different healing modes by establishing different BL. The median BIC of the apical implant part of the zirconia and titanium group amounted to 59.2% for uncoated zirconia, 58.3% for coated zirconia, 26.8% for the synthetic material and 41.2% for titanium implants. Conclusions: Within the limits of this animal study, it is concluded that zirconia implants are capable of establishing close BIC rates similar to what is known from the osseointegration behaviour of titanium implants with the same surface modification and roughness. To cite this article:
Koch FP, Weng D, Krämer S, Biesterfeld S, Jahn‐Eimermacher A, Wagner W. Osseointegration of one‐piece zirconia implants compared with a titanium implant of identical design: a histomorphometric study in the dog.
Clin. Oral Impl. Res. 21 , 2010; 350–356.
doi: 10.1111/j.1600‐0501.2009.01832.x     

In vivo performance of zirconia and titanium implants: a histomorphometric study in mini pig maxillae

Objectives: To compare the bone tissue response to surface‐modified zirconia (ZrO₂) and titanium implants. Methods: Cylindrical low‐pressure injection moulded zirconia (ZrO₂) implants were produced with an acid‐etched surface. Titanium implants with identical shape, sandblasted and acid‐etched surface (SLA) served as controls. Eighteen adult miniature pigs received both implant types in the maxilla 6 months after extraction of the canines and incisors. The animals were euthanized after 4, 8 and 12 weeks and 16 zirconia and 18 titanium implants with the surrounding tissue were retrieved, embedded in methylmethacrylate and stained with Giemsa–Eosin. The stained sections were digitized and histomorphometrically analysed with regard to peri‐implant bone density (bone volume/total volume) and bone–implant contact (BIC) ratio. Statistical analysis was performed using Mann–Whitney' U‐test. Results: Histomorphometrical analysis showed direct osseous integration for both materials. ZrO₂ implants revealed mean peri‐implant bone density values of 60.4% (SD ± 9.9) at 4 weeks, 65.4% (SD ± 13.8) at 8 weeks, and 63.3% (SD ± 21.5) at 12 weeks after implantation, whereas Ti‐SLA implants demonstrated mean values of 61.1% (SD ± 6.2), 63.6% (SD ± 6.8) and 68.2% (SD ± 5.8) at corresponding time intervals. Concerning the BIC ratio, the mean values for ZrO₂ ranged between 67.1% (SD ± 21.1) and 70% (SD ± 14.5) and for Ti‐SLA between 64.7% (SD ± 9.4) and 83.7% (SD ± 10.3). For the two parameters investigated, no significant differences between both types of implants could be detected at any time point. Conclusion: The results indicate that there was no difference in osseointegration between ZrO₂ implants and Ti‐SLA controls regarding peri‐implant bone density and BIC ratio. To cite this article :
Gahlert M, Roehling S, Sprecher CM, Kniha H, Milz S, Bormann K. In vivo performance of zirconia and titanium implants: a histomorphometric study in mini pig maxillae.
Clin. Oral Impl. Res. 23 , 2012; 281–286.
doi: 10.1111/j.1600‐0501.2011.02157.x