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Notes: Abstract Bone morphogenetic protein 2A (BMP2A), a member of the decapentaplegic-Vg-related family, belongs to the transforming growth factor β superfamily and has a striking sequence similarity to the decapentaplegic locus in Drosophila melanogaster, a major determinant of pattern specification during embryogenesis. BMP2A is thought to be involved in cartilage and bone formation during embryogenesis, but may have additional functions in morphogenesis as implied by its expression in various organs and embryonic tissues of mice. Human BMP2A, assigned to chromosome 20 by the use of humanChinese hamster ovary cell hybrids, is considered to be a reasonable candidate gene for the autosomal dominant disease of fibrodysplasia (myositis) ossificans progressiva. We have confirmed the localization of BMP2A to chromosome 20 and regionally assigned the locus to 20pl2 by radioactive and nonradioactive in situ hybridization.

Notes: Abstract. The objective of this study was to evaluate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) concentration on regeneration of alveolar bone and cementum, and on associated root resorption and ankylosis. Contralateral, critical size, supra-alveolar, periodontal defects were surgically produced and immediately implanted with rhBMP-2 in an absorbable collagen sponge (ACS) carrier in 8, young adult, male, beagle dogs. 6 animals received rhBMP-2/ACS (rhBMP-2 at 0.05, 0.10, or 0.20 mg/mL; total construct volume/defect ˜4.0 mL) in contralateral defects following an incomplete block design. 2 animals received rhBMP-2/ACS (rhBMP-2 at 0 and 0.10 mg/mL) in contralateral defects (controls). The animals were euthanised at 8 weeks post-surgery and block sections of the defects were collected for histologic and histometric analysis. Supra-alveolar periodontal defects receiving rhBMP-2 at 0.05, 0.10, or 0.20 mg/ml exhibited extensive alveolar regeneration comprising 86%, 96%, and 88% of the defect height, respectively. Cementum regeneration encompassed 8%, 6%, and 8% of the defect height, respectively. Root resorption was observed for all rhBMP-2 concentrations. Ankylosis was observed in almost all teeth receiving rhBMP-2. Control defects without rhBMP-2 exhibited limited, if any, evidence of alveolar bone and cementum regeneration, root resorption, or ankylosis. Within the selected rhBMP-2 concentration and observation interval, there appear to be no meaningful differences in regeneration of alveolar bone and cementum. There also appear to be no significant differences in the incidence and extent of root resorption and ankylosis, though there may be a positive correlation with rhBMP-2 concentration.

Notes: Objectives: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been shown to stimulate alveolar bone and cementum formation in periodontal defects but not a functionally oriented periodontal ligament (PDL). Subcutaneous and intramuscular implants of BMP-12 have been shown to induce tendon formation and ligament-like tissue. The objective of this study was to evaluate rhBMP-12 for periodontal regeneration, in particular PDL formation.Methods: Six young adult Hound Labrador mongrel dogs were used. Routine supraalveolar periodontal defects were created around the mandibular premolar teeth. Three animals received rhBMP-12(0.04 mg/ml) in an absorbable collagen sponge (ACS) carrier vs. rhBMP-12(0.2 mg/mL)/ACS in contralateral defects. Three animals received rhBMP-12(1.0 mg/ml)/ACS vs. rhBMP-2(0.2 mg/ml)/ACS (total implant volume/defect ∼1 ml). The animals were euthanized 8 weeks postsurgery and block biopsies were processed for histometric analysis.Results: Bone regeneration appeared increased in sites receiving rhBMP-2/ACS compared to sites receiving rhBMP-12/ACS. Cementum regeneration was similar comparing sites implanted with rhBMP-2/ACS to sites implanted with rhBMP-12/ACS. In contrast, sites receiving rhBMP-12/ACS exhibited a functionally oriented PDL bridging the gap between newly formed bone and cementum whereas this was a rare observation in sites receiving rhBMP-2/ACS. Ankylosis appeared increased in sites receiving rhBMP-2/ACS compared to those receiving rhBMP-12/ACS.Conclusions: The outcomes of this study suggest that rhBMP-12 may have significant effects on regeneration of the PDL. Additional preclinical evaluation is needed to confirm these initial observations prior to clinical application.

Notes: Objectives: Subcutaneous and intramuscular implants of bone morphogenetic protein-12 (BMP-12) have been shown to induce formation of tendon and ligament tissue. BMP-12 induced a new attachment with a distinct fibrocartilaginous zone at the tendon-bone interface in the rat tendon-bone attachment model. Surgical controls showed poor healing and failure to reform the appropriate tendon–bone attachment morphologically. Application of recombinant human BMP-12 (rhBMP-12) to periodontal defects suggests that rhBMP-12 has the potential to support regeneration of the periodontal ligament (PDL). The objective of this pilot study was to evaluate this effect of rhBMP-12 in a tooth replantation model.Methods: Six, young adult, male Hound Labrador mongrel dogs were used. Maxillary and/or mandibular incisor and premolar teeth were extracted and the PDL was either left “intact” or removed by root planing. rhBMP-12 (1.0 mg/ml) or a buffer control was topically applied to teeth with “intact” PDL in contralateral jaw quadrants in each of 3 animals. The teeth were immersed in 1.0 ml of the rhBMP-12 or the buffer solution for 10 min and then replanted. The remaining three animals received rhBMP-12 (1.0 mg/ml) and the buffer control in a similar fashion applied to teeth instrumented to remove the PDL and cementum, and surface demineralized with citric acid. The animals were euthanized at 8 weeks postsurgery and block sections were collected and processed for histopathologic analysis.Results: No dramatic differences were found between teeth receiving topical rhBMP-12 and the buffer control. Application of rhBMP-12 did not have an apparent effect on new cementum and PDL formation in the tooth replantation model. Moreover, application of rhBMP-12 did not increase nor did it decrease the apparent presence and extent of ankylosis along the root surface compared to the control.Conclusions: The observations from this study do not support the use of topical rhBMP-12 to support the reestablishment of the PDL including regeneration of cementum and functionally oriented fibers, and to prevent ankylosis and root resorption following replantation of teeth.

Notes: Background: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been shown to induce clinically relevant bone formation for orthopedic, craniofacial, and oral indications. It appears critical, in particular for onlay indications, that the associated carrier technology exhibits structural integrity to offset compressive forces in support of rhBMP-2-induced bone formation. The objective of this study was to evaluate a calcium phosphate (CP) cement, Ceredex™, as a candidate carrier for rhBMP-2 in a defect model with limited osteogenic potential.Materials: Bilateral, critical size, 6-mm, supra-alveolar, periodontal defects were created in six, adult, male, Hound Labrador mongrels. Three animals received rhBMP-2/Ceredex™ (rhBMP-2 at 0.20 and 0.40 mg/ml) in contralateral defect sites (implant volume/defect ∼1 ml). One defect site in each of the three remaining animals received Ceredex™ without rhBMP-2 (control). The animals were euthanized at 12 weeks postsurgery for histologic and histometric analysis.Results: Mean induced bone height exceeded 80% of the defect height for supra-alveolar periodontal defects receiving rhBMP-2/Ceredex™ without major differences between rhBMP-2 concentrations compared with approximately 40% for the control. The newly formed bone, a mixture of lamellar and woven bone in fibrovascular tissue, circumscribed relatively large portions of the residual Ceredex™ biomaterial. Inflammatory lesions were associated with limited bone formation in some sites. From a periodontal perspective, sites receiving rhBMP-2/Ceredex™ exhibited increased cementum formation compared with control, but without a functionally oriented periodontal ligament, and increased ankylosis and root resorption. Control sites exhibited early wound failure and exposure, loss of the Ceredex™ biomaterial, and limited bone formation.Conclusions: The Ceredex™ CP cement appears a potentially promising carrier technology for rhBMP-2 onlay indications. However, a slow resorption rate may prevent its wider use. This study does not support use of the rhBMP-2/Ceredex™ combination for periodontal indications.

Notes: Abstract Background: Previous studies have shown a limited potential for bone augmentation following guided bone regeneration (GBR) in horizontal alveolar defects. Surgical implantation of recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge carrier (ACS) significantly enhances bone regeneration in such defects; however, sufficient quantities of bone for implant dentistry are not routinely obtained. The objective of this study was to evaluate the potential of rhBMP-2/ACS to enhance GBR using a space-providing, macro-porous expanded polytetrafluoroethylene (ePTFE) device.Methods: Bilateral, critical size, supra-alveolar, peri-implant defects were surgically created in four Hound Labrador mongrel dogs. Two turned and one surface-etched 10-mm titanium dental implant were placed 5 mm into the surgically reduced alveolar ridge creating 5-mm supra-alveolar defects. rhBMP-2/ACS (rhBMP-2 at 0.2 mg/ml) or buffer/ACS was randomly assigned to left and right jaw quadrants in subsequent animals. The space-providing, macro-porous ePTFE device was placed to cover rhBMP-2/ACS and control constructs and dental implants. Gingival flaps were advanced for primary wound closure. The animals were euthanized at 8 weeks postsurgery for histologic and histometric analysis.Results: Bone formation was significantly enhanced in defects receiving rhBMP-2/ACS compared to control. Vertical bone gain averaged (±SD) 4.7±0.3 and 4.8±0.1 mm, and new bone area 10.3±2.0 and 8.0±2.5 mm2 at turned and surface-etched dental implants, respectively. Corresponding values for the control were 1.8±2.0 and 1.3±1.3 mm, and 1.8±1.3 and 1.2±0.6  mm2. Bone–implant contact in rhBMP-2-induced bone averaged 6.4±1.4% and 9.6±7.5% for turned and surface-etched dental implants, respectively (P=0.399). Corresponding values for the control were 14.6±19.4% and 23.7±9.7% (P=0.473). Bone–implant contact in resident bone ranged between 43% and 58% without significant differences between dental implant surfaces.Conclusions: rhBMP-2/ACS significantly enhances GBR at turned and surface-etched dental implants. The dental implant surface technology does not appear to substantially influence bone formation.

Notes: Abstract: Osseointegration [direct bone–implant contact (BIC)] is a primary goal following installation of endosseous dental implants. Such bone contact provides stability for the dental implant over time. The objective of this study was to evaluate bone formation and BIC at long-term, functionally loaded, endosseous dental implants placed into bone induced by recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS) carrier. Mandibular, saddle-type, alveolar ridge defects (∼15 × 10 × 10 mm), two per jaw quadrant, were surgically induced in each of six young adult American fox hounds. The defects were immediately implanted with rhBMP-2/ACS. Two defects per animal additionally received a nonresorbable expanded polytetrafluoroethylene (ePTFE) membrane or a bioresorbable polyglycolide fiber membrane. Healing was allowed to progress for 3 months, when the ePTFE membrane was removed, and machined, threaded, titanium dental implants were installed into the rhBMP-2/ACS induced bone and into the adjacent resident bone. At 4 months of osseointegration, the implants were exposed to receive abutments and prosthetic treatment (two- or three-unit bridges). Some implants were removed for histologic analysis. The remainder of implants were exposed to functional loading for 12 months at which time the animals were killed for histometric analysis. One animal died prematurely due to kidney failure unrelated to the experimental protocol and was not included in the analysis. The 12-month block sections from a second animal were lost in the histological processing. Four sites receiving rhBMP-2/ACS and ePTFE or resorbable membranes experienced wound failure and membrane exposure, and subsequently exhibited limited bone formation. Defects without wound failure filled to contour with the adjacent alveolar bone. The newly formed bone exhibited features of the resident bone with a re-established cortex; however, it commonly included radiolucent areas that resolved over time. Dental implants block biopsied at 4 months exhibited limited, if any, crestal resorption, whereas those exposed to functional loading for 12 months exhibited some crestal resorption. Implants biopsied at 4 months exhibited a mean (± SD) BIC of 40.6 ± 8.2% in rhBMP-2/ACS induced bone vs. 52.7 ± 11.4% in resident bone. Dental implants exposed to 12 months of functional loading exhibited a mean BIC of 51.7 ± 7.1% in rhBMP-2/ACS induced bone vs. 74.7 ± 7.0% in resident bone. There were no significant differences between dental implants placed into rhBMP-2/ACS induced bone and resident bone for any parameter at any observation interval. In conclusion, rhBMP-2/ACS-induced bone allows installation, osseointegration, and long-term functional loading of machined, threaded, titanium dental implants in dogs.

Notes: The objective of this study was to evaluate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) dose on alveolar ridge augmentation and dental implant osseointegration. Bilateral, 5 mm supraalveolar, peri-implant defects were surgically created in 6 beagle dogs. rhBMP-2 (0.05, 0.1 or 0.2 mg/ml) in an absorbable collagen sponge (ACS) carrier was molded around the fixtures and wounds were closed. Treatment variations were alternated between animals (incomplete block design). Animals were sacrificed at week 8 postsurgery. Nine of twelve jaw quadrants healed uneventfully. Two jaw quadrants exhibited wound failure by week 4 and one by week 8 postsurgery. Radiographic bone regeneration was observed in defects without wound failure from week 4 postsurgery. Radiolucent voids of variable size and shape were observed and regressed over time. In weeks 6 through 8, there was an apparent increase in bone density and trabecular structure, while bone height and volume decreased. Histometric analysis revealed limited differences in bone regeneration between experimental conditions. Bone regeneration area averaged (±SD) 1.0±0.5, 3.5± 1.4 and 2.3±0.4 mm2 for the 0.05, 0.1 and 0.2 mg/ml dose, respectively. There were no significant differences in osseointegration. Osseointegration in newly formed bone averaged 19± 4%, 18± 10% and 21±6% for the 0.05, 0.1 and 0.2 mg/ml rhBMP-2 sites, respectively. Collectively, the data suggest that there are no dramatic differences in bone induction and osseointegration within the selected dose and observation interval.