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 ( approximately 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.

Observations on healing following endodontic surgery in nonhuman primates (Macaca fascicularis): effects of rhBMP-2.

OBJECTIVES: The potential of recombinant human bone morphogenetic protein-2 (rhBMP-2) to enhance bone healing following endodontic surgery was tested. The pattern and timing of de novo bone formation and cementum regeneration, and the potential for root resorption and ankylosis to accompany bone formation were evaluated. STUDY DESIGN: Pulpal infections were induced in maxillary and mandibular incisor teeth in young adult Cynomolgus monkeys. The teeth received conventional endodontic treatment immediately followed by surgical root resection. In a randomized split-mouth design, contralateral apical bone defects received rhBMP-2 in absorbable collagen sponge (ACS) carrier or served as sham-surgery controls to provide histological and radiographic evaluations following 1 (mandibular incisors) and 4.5 (maxillary incisors) month(s) postsurgery. RESULTS: At 1 month postsurgery trabecular bone filled the apical bone defects. The newly formed bone appeared considerably more mature and had assumed characteristics of the contiguous resident bone at 4.5 months postsurgery. The resected root tips were almost completely covered by new cementum with a maturing functionally oriented periodontal ligament. Localized inflammatory infiltrates were associated with the filled root canals and extruded root-filling material. Root resorption and ankylosis were not observed. There were no apparent differences in healing patterns between sites implanted with rhBMP-2/ACS and those serving as sham-surgery controls. CONCLUSIONS: Under conditions where the influence of infectious elements and irritation caused by root filling material are minimized, bone formation and cementum regeneration appears rapid following endodontic surgery. rhBMP-2/ACS did not offer an obvious benefit above and beyond that of the native osteogenic potential in this animal model.

Bone-implant contact at calcium phosphate-coated and porous titanium oxide (TiUnite)-modified oral implants.

BACKGROUND: Calcium phosphate (CP)-coated implants are usually referred to as having osteoconductive properties, whereas titanium implants with a native oxide layer are considered less osteoconductive. Often smooth titanium oxides (TOs) are compared to relatively rough CP structures. The objective of this study was to evaluate osteoconduction by comparing bone-implant contact at a relatively smooth, highly crystalline CP coating with a structured, porous TO (TiUnite)-modified surface. MATERIAL AND METHODS: Ten adult Hound Labrador mongrel dogs were used. Four titanium implants (Nobel Biocare) with CP-coated (2) or TO-modified (2) surfaces were installed 12 weeks following mandibular premolar and molar teeth extraction. The implants were alternated within and between jaw quadrants in consecutive animals. Mucosal flaps were advanced and sutured leaving the implants in a submerged position. The animals were injected with fluorescent bone labels at 3 and 4 weeks postsurgery, and pre-euthanasia to monitor progress of bone formation. The animals were euthanized at 8 weeks postsurgery and block biopsies were prepared for histologic and histometric analysis. RESULTS: There were no remarkable differences in bone formation and apparent bone-implant contact comparing the TO-modified and CP-coated surfaces. However, the measured average bone-implant contact was 71% and 57% (P=0.027) for TO-modified and CP-coated implants, respectively. CONCLUSIONS: We conclude that the TO surface exhibits osteoconductive properties exceeding that of the CP surface. One or several of the chemical and physical properties of the TO surface may result in the remarkable bone formation along its surface. This study indicated that crystallinity and/or chemistry may be important.

Bone formation at titanium porous oxide (TiUnite) oral implants in type IV bone.

BACKGROUND: Several oral implant design advances have been suggested to overcome poor bone quality, an impediment for successful implant treatment. A novel titanium porous oxide (TPO) surface has been shown to offer favorable results in several settings. The objective of this study was to evaluate the local bone formation and osseointegration at TPO-modified implants in type IV bone. METHOD: Three TPO surface-modified implants (TiUnite) were installed into the edentulated posterior maxilla in each of 8 Cynomolgus monkeys. The animals were injected with fluorescent bone labels at 2, 3, 4 and 16 weeks post-surgery and were euthanized at week 16 when block biopsies were collected for histologic analysis. RESULTS: The predominant observation of the TPO implant surface was a thin layer of new bone covering most of the implant threads. Mean (+/-SE) bone-implant contact for the whole study group was 74.1 +/- 4.8%. There was a significant variability in bone-implant contact between animals (P = 0.0003) and between sites of the same animal (P < 0.0001). The variance in bone-implant contact was 30% larger among sites of the same animal than between different animals (187.5 vs. 144.8, respectively). There was a small but significant difference in bone density immediately outside, compared to within the threaded area of the implants (37.1 +/- 3.2% vs. 32.1 +/- 3.2%, P < 0.0001). Bone density outside the implant threads was significantly correlated (beta = 0.682, P < 0.0001) with the bone density within the threaded area. Bone density within the threaded area was significantly correlated (beta = 0.493, P = 0.0002) with bone-implant contact, whereas bone density outside the implant threads did not have a significant effect (beta = 0.232, P = 0.1). CONCLUSIONS: The results suggest that the TPO surface possesses a considerable osteoconductive potential promoting a high level of implant osseointegration in type IV bone in the posterior maxilla.

Prognostic factors for alveolar regeneration: bone formation at teeth and titanium implants.

OBJECTIVES: There is a limited understanding of the effect of defect characteristics on alveolar bone healing. The objectives of this study were to assess the effect of alveolar bone width and space provision on bone regeneration at teeth and titanium implants, and to test the hypothesis that the regenerative potentials at teeth and implants are not significantly different. METHODS: Critical size, 5-6-mm, supra-alveolar, periodontal defects were surgically created in 10 young adult dogs. Similarly, critical size, 5-mm, supra-alveolar, peri-implant defects were created in four dogs. A space-providing expanded polytetrafluoroethylene device was implanted for guided tissue regeneration/guided bone regeneration. The animals were euthanized at 8 weeks postsurgery. Histometric analysis assessed alveolar bone regeneration (height) relative to space provision by the device and the width of the alveolar crest at the base of the defect. Statistical analysis used the linear mixed models. RESULTS: A significant correlation was found between bone width and wound area (r=0.55892, p<0.0001). Generally, bone width and wound area had statistically significant effects on the extent of bone regeneration (p<0.0005 and p<0.0001, respectively). Bone regeneration was linearly correlated with the bone width at periodontal (p<0.001) and implant (p=0.04) sites, and with the wound area at periodontal (p<0.0001) and implant (p=0.03) sites. The relationships of bone regeneration with these two variables were not significantly different between teeth and implants (bone width: p=0.83; wound area: p=0.09). When adjusted for wound area, bone regeneration was significantly greater at periodontal than at implant sites (p=0.047). CONCLUSIONS: The horizontal dimension of the alveolar bone influences space provision. Space provision and horizontal dimension of the alveolar bone appear to be important determinants of bone regeneration at teeth and implants. The extent of alveolar bone formation at implant sites is limited compared with that at periodontal sites.

Prognostic factors for alveolar regeneration: effect of a space-providing biomaterial on guided tissue regeneration.

OBJECTIVES: There is a limited understanding of the effect of bone biomaterials on the healing potential when used in conjunction with guided tissue regeneration (GTR). The objective of this study was to evaluate the effect of a space-providing coral-derived biomaterial on alveolar bone regeneration in conjunction with GTR. METHODS: Bilateral, critical-size, 6-mm, supra-alveolar, periodontal defects were created in four young adult Beagle dogs. In a split-mouth design, the animals received an ePTFE device to provide for GTR in contralateral defect sites with or without the coral biomaterial. The animals were euthanized at 4 weeks post surgery. A histometric analysis assessed vertical regeneration of alveolar bone relative to space-provision by the ePTFE device. Because of the correlation of within-dog measurements, a mixed model ANOVA was used to analyze the data. RESULTS: There was significantly greater mean bone regeneration in sites receiving calcium carbonate coral implant GTR (cGTR) compared to GTR (p < 0.0001). Sites providing larger wound areas exhibited greater bone regeneration compared to sites exhibiting smaller wound areas (p < 0.0001). However, grouping the sites by wound area thresholds showed that bone regeneration was not significantly different in sites receiving cGTR compared to sites receiving GTR alone, irrespective of the size of the wound area (p > 0.5). CONCLUSIONS: Space-provision has a significant effect on bone regeneration following GTR. The coral biomaterial effectively enhances space-provision, and this appears to be the principal mechanism by which this biomaterial supports bone regeneration rather than postulated osteoconductive properties.

Prognostic factors for alveolar regeneration: effect of tissue occlusion on alveolar bone regeneration with guided tissue regeneration.

OBJECTIVES: Design criteria for guided tissue regeneration (GTR) devices include biocompatibility, cell occlusion, space-provision, tissue integration, and ease of use. The objective of this study was to evaluate the effect of cell occlusion and space-provision on alveolar bone regeneration in conjunction with GTR. METHODS: Routine, critical-size, 6 mm, supra-alveolar, periodontal defects were created in 6 young adult Beagle dogs. Space-providing ePTFE devices, with or without 300-microm laser-drilled pores were implanted to provide for GTR. Treatments were alternated between left and right jaw quadrants in subsequent animals. The gingival flaps were advanced for primary intention healing. The animals were euthanized at week 8 post surgery. The histometric analysis assessed regeneration of alveolar bone relative to space-provision by the ePTFE device. RESULTS: A significant relationship was observed between bone regeneration and space-provision for defect sites receiving the occlusive (beta = 0.194; p < 0.02) and porous (beta = 0.229; p < 0.0004) GTR devices irrespective of treatment (p = 0.14). The bivariate analysis showed that both space-provision and device occlusivity significantly enhanced bone regeneration. Hence, sites receiving the occlusive GTR device and sites with enhanced space-provision showed significantly greater bone regeneration compared to sites receiving the porous GTR device (p = 0.03) or more limited space-provision (p = 0.0002). CONCLUSIONS: Cell occlusion and space-provision may significantly influence the magnitude of alveolar bone regeneration in conjunction with guided tissue regeneration.

Periodontal repair in dogs: rhBMP-2 significantly enhances bone formation under provisions for guided tissue regeneration.

BACKGROUND: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been shown to support the regeneration of alveolar bone and periodontal attachment in surgically created periodontal defects and in defects with a history of dental plaque and calculus exposure. Periodontal regeneration has also been shown following guided tissue regeneration using space-providing expanded polytetrafluoroethylene (ePTFE) devices. The objective of this study was to evaluate the influence of rhBMP-2 on regeneration of alveolar bone and periodontal attachment used in conjunction with a space-providing ePTFE device. METHODS: Routine, critical-size, 5-6 mm, supra-alveolar, periodontal defects were created around the third and fourth mandibular premolar teeth in four young adult Hound Labrador mongrel dogs. rhBMP-2 (0.2 mg/ml) in an absorbable collagen sponge (rhBMP-2/ACS) or buffer/ACS (control) implants were randomly assigned to be placed around the premolar teeth in the left and right jaw quadrants in subsequent animals. Space-providing ePTFE devices with 300-microm laser-drilled pores, 0.8 mm apart, were used to cover the rhBMP-2 and control implants. The gingival flaps were advanced for primary wound closure. The animals were euthanized at 8 weeks postsurgery for histologic and histometric analyses. RESULTS: Bone regeneration and ankylosis were significantly increased in jaw quadrants receiving rhBMP-2/ACS compared to control (bone height 4.8+/-0.3 versus 2.0+/-0.2 mm, p=0.001; bone area 10.9+/-1.3 versus 1.4+/-0.1 mm2; p=0.009, and ankylosis 2.2+/-0.2 versus 0.04+/-0.7 mm; p=0.01). No differences between groups were found for cementum regeneration and root resorption. CONCLUSIONS: rhBMP-2 significantly enhances regeneration of alveolar bone in conjunction with a space-providing, macroporous ePTFE device for GTR.

Periodontal repair in dogs: space-providing ePTFE devices increase rhBMP-2/ACS-induced bone formation.

BACKGROUND: Recombinant human bone morphogenetic protein-2 (rhBMP-2) technologies have been shown to enhance alveolar bone formation significantly. Biomaterial (carrier) limitations, however, have restricted their biologic potential for indications where compressive forces may limit the volume of bone formed. The objective of this proof-of-principle study was to evaluate the potential of a space-providing, macroporous ePTFE device to define rhBMP-2-induced alveolar bone formation using a discriminating onlay defect model. METHODS: Routine, critical size, 5-6 mm, supra-alveolar, periodontal defects were created around the third and fourth mandibular premolar teeth in four young adult Hound Labrador mongrel dogs. All jaw quadrants received rhBMP-2 (0.4 mg) in an absorbable collagen sponge (ACS) carrier. Contralateral jaw quadrants in subsequent animals were randomly assigned to receive additionally the dome-shaped, macroporous ePTFE device over the rhBMP-2/ACS implant or no additional treatment. The gingival flaps were advanced to cover the ePTFE device and teeth, and sutured. Animals were scheduled for euthanasia to provide for histologic observations of healing at 8 weeks postsurgery. RESULTS: Healing was uneventful without device exposures. New bone formation averaged (+/-SD) 4.7+/-0.2 mm (98%) and 4.5+/-0.4 mm (94%) of the defect height, respectively, for jaw quadrants receiving rhBMP-2/ACS with the ePTFE device or rhBMP-2/ACS alone (p>0.05). In contrast, the regenerated bone area was significantly enhanced in jaw quadrants receiving rhBMP-2/ACS with the ePTFE device compared to rhBMP-2/ACS alone (9.3+/-2.7 versus 5.1+/-1.1 mm2; p<0.05). Cementum formation was similar for both treatment groups. Ankylosis compromised periodontal regeneration in all sites. CONCLUSIONS: The results suggest that the novel space-providing, macroporous ePTFE device appears suitable as a template to define rhBMP-2/ACS-induced alveolar bone formation.