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.

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 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: 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.