Use of a Collagen Membrane Loaded With Recombinant Human Bone Morphogenetic Protein‐2 With Collagen‐Binding Domain for Vertical Guided Bone Regeneration

Background: Vertical bone regeneration of severe atrophic alveolar ridges remains a challenging procedure in implant dentistry. Methods: The aim of this study, accordingly, is to use a rabbit vertical guided bone regeneration model to evaluate whether using a collagen membrane (CM) loaded with small doses of recombinant human bone morphogenetic protein‐2 with collagen‐binding domain (rhBMP‐2/CBD) would enhance two‐way vertical bone regeneration. In each of eight rabbits, four titanium cylinders were screwed in perforated slits made into the external cortical bones of the calvaria. The following four treatment modalities were randomly allocated: 1) cylinders filled with mineralized bone matrix and covered with CM/rhBMP‐2/CBD; 2) cylinders filled with mineralized bone matrix and covered with CM/rhBMP‐2; 3) cylinders filled with mineralized bone matrix and covered with CM alone; or 4) cylinders filled with mineralized bone matrix without a membrane cover. Results: After 6 weeks, the new bones were examined by histologic analysis. Slender new bone trabeculae were observed in the superficial layer of the titanium cylinders covered with CM/rhBMP‐2/CBD, and higher degrees of bone were observed in this group compared with the other three groups. The average area fraction of newly formed bone was significantly more in the CM/rhBMP‐2/CBD group compared with the CM/rhBMP‐2, CM, or the no membrane control groups (all P <0.01). Conclusions: The present study demonstrates that CMs loaded with small doses of rhBMP‐2/CBD induce new bone formation not only from the surface of the native bone, but also from the superficial structures. The augmented new bone, therefore, is improved in both quantity and quality.     

Effects of Recombinant Human Bone Morphogenetic Protein‐2 on Vertical Bone Augmentation in a Canine Model

Background: Vertical bone augmentation (VBA) remains unpredictable and challenging for most clinicians. This study aims to compare hard tissue outcomes of VBA, with and without recombinant human bone morphogenetic protein (rhBMP)‐2, under space‐making titanium mesh in a canine model. Methods: Eleven male beagle dogs were used in the study. Experimental ridge defects were created to form atrophic ridges. VBA was performed via guided bone regeneration using titanium mesh and allografts. In experimental hemimandibles, rhBMP‐2/absorbable collagen sponge was well mixed with allografts prior to procedures, whereas a control buffer was applied within controls. Dogs were euthanized after a 4‐month healing period. Clinical and radiographic examinations were performed to assess ridge dimensional changes. In addition, specimens were used for microcomputed tomography (micro‐CT) assessment and histologic analysis. Results: Membrane exposure was found on five of 11 (45.5%) rhBMP‐2–treated sites, whereas it was found on nine of 11 (81.8%) non–rhBMP‐2–treated sites. Within 4 months of healing, rhBMP‐2–treated sites showed better radiographic bone density, greater defect fill, and significantly more bone gain in ridge height (P <0.05) than controls. Experimental hemimandibles exhibited lower rates of membrane exposure and a noteworthy, ectopic bone formation above the mesh in 72% of sites. Results from micro‐CT also suggested a trend of less vertical bone gain and bone mineral density in controls (P >0.05). Under light microscope, predominant lamellar patterns were found in the specimen obtained from rhBMP‐2 sites. Conclusion: With inherent limitations of the canine model and the concern of such a demanding surgical technique, current findings suggest that the presence of rhBMP‐2 in a composite graft allows an increase of vertical gain, with formation of ectopic bone over the titanium mesh in comparison with non–rhBMP‐2 sites.     

Evaluation of Healing Following Tooth Extraction With Ridge Preservation Using Cortical Versus Cancellous Freeze‐Dried Bone Allograft

Background: The objective of this study is to compare histologic and clinical healing following tooth extraction and ridge preservation with either cortical or cancellous freeze‐dried bone allograft (FDBA) in non‐molar extraction sockets. Methods: Forty patients requiring implant placement were enrolled, with 20 patients randomly assigned to each group (cortical versus cancellous FDBA). All of the allograft materials were obtained from the same donor to control for variability between donors and processing. Patients returned after 17 to 21 weeks (average: 18.2 weeks), and a 2‐mm‐diameter core biopsy was obtained before implant placement. Histomorphometric analysis was performed to determine percentage of new bone formation, residual graft material, and non‐mineralized connective tissue (CT)/other material. Clinical measurements of ridge dimensions were taken at the time of tooth extraction and again at implant placement. Results: There was no significant difference in new bone formation between the cortical and cancellous FDBA groups (P = 0.857). A significantly greater percentage of residual graft material was detected in the cortical FDBA group compared with the cancellous FDBA group (P = 0.019). A significantly greater percentage of non‐mineralized CT/other material was found in the cancellous FDBA group compared with the cortical FDBA group (P = 0.040). The only significant clinical difference between groups was a greater loss of lingual ridge height in the cancellous group. Conclusions: This is the first reported study to compare the histologic changes following tooth extraction with ridge preservation in humans using cortical versus cancellous FDBA. There were no differences in the percentage of new bone formation between the groups.     

Accelerated Bone Formation in Distracted Alveolar Bone After Injection of Recombinant Human Bone Morphogenetic Protein‐2

Background: This study evaluates the effect of recombinant human bone morphogenetic protein‐2 (rhBMP‐2) on the quality and quantity of regenerated bone when injected into distracted alveolar bone. Methods: Sixteen adult beagle dogs were assigned to either the control or rhBMP‐2 group. After distraction was completed, an rhBMP‐2 dose of 330 μg in 0.33 mL was injected slowly into the distracted alveolar crest of the mesial, middle, and distal parts of the alveolar bone in the experimental group. Histologic and microcomputed tomography analyses of regenerated bone were done after 2 and 6 weeks of consolidation. Results: After 6 weeks of consolidation, the vertical defect height in the middle of the regenerated bone was significantly lower in the rhBMP‐2 group (2.2 mm) than in the control group (3.4 mm) (P <0.05). Additionally, the width of the regenerated bone was significantly greater in the rhBMP‐2 group (4.3 mm) than in the control group (2.8 mm) (P <0.05). The bone density and volume of regenerated bone in the rhBMP‐2 group were greater than in the control group after 6 weeks of consolidation (P <0.001). Conclusion: Injection of rhBMP‐2 into regenerated bone after a distraction osteogenesis procedure significantly increased bone volume in the dentoalveolar distraction site and improved both the width and height of the alveolar ridge and increased the bone density.     

Ex Vivo Bone Morphogenetic Protein‐2 Gene Delivery Using Bone Marrow Stem Cells in Rabbit Maxillary Sinus Augmentation in Conjunction With Implant Placement

Background: This study evaluates the potential of bone morphogenetic protein 2 (BMP‐2) gene–transduced bone marrow stem cells (BMSCs) to facilitate osseous healing after rabbit maxillary sinus augmentation in conjunction with implant placement. Methods: Autologous BMSCs derived from New Zealand white rabbits were cultured and transduced with BMP‐2 using an adenovirus vector. Transduced BMSCs (BMP‐2/BMSCs) were then combined with a deproteinized bovine bone mineral (DBBM) scaffold. Twenty‐seven animals were randomly allocated into three groups: 1) control, sinus grafted with DBBM alone; 2) BMSC, sinus grafted with non‐transduced BMSCs and DBBM; and 3) BMP‐2/BMSC, sinus grafted with BMP‐2/BMSCs and DBBM. During these procedures, a mini‐implant was placed in the floor of the sinus. Animals were sacrificed at 2, 4, and 8 weeks after surgery. New bone area and bone‐to‐implant contact (BIC) were evaluated histomorphometrically. Results: At 2 and 4 weeks, the BMP‐2/BMSC group showed more new bone area and higher BIC than the other two groups. BMP‐2/BMSCs were detected with confocal microscopy for up to 4 weeks, which indicates that transduced cells contributed to new bone formation. However, at 8 weeks, there was no difference in new bone area or BIC among the three groups. Conclusions: These results suggest that BMP‐2 delivery using BMSCs may result in earlier and increased bone formation in the maxillary sinus. This finding may offer more stable bone support to implants and reduce healing times. However, this study also revealed limitations in the stimulatory effect of BMP‐2/BMSCs, such as diminished activity over time in later healing stages.     

Interventions for Dental Implant Placement in Atrophic Edentulous Mandibles: Vertical Bone Augmentation and Alternative Treatments. A Meta‐Analysis of Randomized Clinical Trials

Background: The purpose of the current study is to assess which vertical bone augmentation techniques are most effective for restoring atrophic posterior areas of the mandible with dental implants and compare these procedures with alternative treatments. Methods: Electronic literature searches in PubMed (MEDLINE), Ovid, and the Cochrane Library were conducted to identify all relevant articles published up to July 1, 2015. Eligibility was based on inclusion criteria, and quality assessments were conducted. The primary outcome variables were implant and prosthetic failure. After data extraction, meta‐analyses were performed. Results: Out of 527 potentially eligible papers, 14 randomized clinical trials were included. Out of these 14 studies, four trials assessed short implants (5 to 8 mm) as an alternative to vertical bone augmentation in sites with a residual ridge height of 5 to 8 mm. No statistically significant differences were found in implant (odds ratio [OR]: 1.02; 95% confidence interval [CI]: 0.31 to 3.31; P = 0.98; I²: 0%) or prosthetic failure (OR: 0.64; 95% CI: 0.21 to 1.96; P = 0.43; I²: 0%) after 12 months of loading. However, complications at treated sites increased with the augmentation procedures (OR: 8.33; 95% CI: 3.85 to 20.0; P <0.001; I²: 0%). There was no evidence of any vertical augmentation procedure being of greater benefit than any other for the primary outcomes (implant and prosthetic failure). Conclusions: Short implants in the posterior area of the mandible seem to be preferable to vertical augmentation procedures, which present similar implant and prosthetic failure rates but greater morbidity. All the vertical augmentation technique comparisons showed similar intergroup results.     

Biodegradation Property of Beta‐Tricalcium Phosphate‐Collagen Composite in Accordance with Bone Formation: A Comparative Study with Bio‐Oss Collagen® in a Rat Critical‐Size Defect Model

Purpose: The objective of this study was to compare osteoconductivity and biodegradation properties of an in‐house fabricated beta‐tricalcium phosphate (b‐TCP)‐collagen composite with those of Bio‐Oss Collagen® (Osteohealth, Shirley, NY, USA) using a rat calvarial critical‐size defect model. Materials and Methods: b‐TCP–collagen composite material was fabricated by mixing b‐TCP granules having a particle size of 0.15 to 0.8 mm and 75% porosity, with bovine dermis‐derived soluble collagen sponge. The dry weight ratio of b‐TCP granules‐to‐collagen ratios was 4:1. Bio‐Oss Collagen or the b‐TCP–collagen composite was used to fill a 5.0 mm–diameter calvarial defect in rats. The defects were evaluated by histological and histomorphological analyses of decalcified histological sections with hematoxylin and eosin staining 6 and 10 weeks, respectively, after surgery. Results: The defect implanted with the b‐TCP composite contained immature bone structures with dense connective tissue in contrast to the abundant fibrous tissue, but no trabecular structure was observed within the defect implanted with Bio‐Oss Collagen at 6 weeks postoperatively. Eventually, the defect filled with the b‐TCP composite was covered with dense, continuous, mature bone tissue with complete replacement of the graft material. However, in defects filled with Bio‐Oss Collagen, only dense connective tissue, containing limited amounts of immature trabecular bone and abundant remnant Bio‐Oss particles, was observed. Histomorphological analysis revealed that the b‐TCP composite caused greater tissue augmentation with a larger volume of bone tissue observed in the defect and greater bioabsorption of remnant material than Bio‐Oss Collagen. Conclusion: These results indicated that the b‐TCP composite has greater osteoconductivity and better biodegradation properties than Bio‐Oss Collagen; these properties of the b‐TCP–collagen composite complimented bone formation and remodeling.