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.     

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

Background: Studies using ectopic rodent, orthotopic canine, and non‐human primate models show that bone morphogenetic proteins (BMPs) coated onto titanium surfaces induce local bone formation. The objective of this study was to examine the ability of recombinant human BMP‐2 (rhBMP‐2) coated onto a titanium porous oxide implant surface to stimulate local bone formation including osseointegration and vertical augmentation of the alveolar ridge. Material and Methods: Bilateral, critical‐size, 5 mm, supra‐alveolar, peri‐implant defects were created in 12 young adult Hound Labrador mongrel dogs. Six animals received implants coated with rhBMP‐2 at 0.75 or 1.5 mg/ml, and six animals received implants coated with rhBMP‐2 at 3.0 mg/ml or uncoated control. Treatments were randomized between jaw quadrants. The mucoperiosteal flaps were advanced, adapted and sutured to submerge the implants for primary intention healing. The animals received fluorescent bone markers at weeks 3, 4, 7 and 8 post‐surgery when they were euthanized for histologic evaluation. Results: Jaw quadrants receiving implants coated with rhBMP‐2 exhibited gradually regressing swelling that became hard to palpate disguising the contours of the implants. The histologic evaluation showed robust bone formation reaching or exceeding the implant platform. The newly formed bone exhibited characteristics of the adjoining resident Type II bone including cortex formation for sites receiving implants coated with rhBMP‐2 at 0.75 or 1.5 mg/ml. Sites receiving implants coated with rhBMP‐2 at 3.0 mg/ml exhibited more immature trabecular bone formation, seroma formation and peri‐implant bone remodelling resulting in undesirable implant displacement. Control implants exhibited minimal, if any, bone formation. Thus, implants coated with rhBMP‐2 at 0.75, 1.5 and 3.0 mg/ml exhibited significant bone formation (height and area) compared with the sham‐surgery control averaging (±SD) 4.4±0.4, 4.2±0.7 and 4.2±1.2 versus 0.8±0.3 mm; and 5.0±2.2, 5.6±2.2 and 7.4±3.5 versus 0.7±0.3 mm², respectively (p<0.01). All the treatment groups exhibited clinically relevant osseointegration. Conclusions: rhBMP‐2 coated onto titanium porous oxide implant surfaces induced clinically relevant local bone formation including vertical augmentation of the alveolar ridge and osseointegration. Higher concentrations/doses were associated with untoward effects.     

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.     

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.     

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.     

rhBMP-2 significantly enhances guided bone regeneration

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.     

Long-term functional loading of dental implants in rhBMP-2 induced bone. A histologic study in the canine ridge augmentation model

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 (approximately 15 x 10 x 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.     

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.     

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.     

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.     

Effect of recombinant human bone morphogenetic protein-2 in dehiscence defects with non-submerged immediate implants: an experimental study in Cynomolgus monkeys

BACKGROUND: Alveolar ridge aberrations commonly compromise optimal dental implant installation. To offset any variance between an aberrant alveolar ridge and prosthetic designs, bone augmentation procedures become necessary. The objective of this study was to evaluate bone formation and osseointegration at alveolar dehiscence defects following augmentation of the defect site with recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge carrier (ACS) at dental implant installation including transmucosal positioning of the dental implant. METHODS: Four adult male Cynomolgus monkeys received dental implants in contralateral extraction socket sites with surgically created 6 x 4 mm buccal dehiscence defects following elevation of mucoperiosteal flaps. Contralateral sites received rhBMP-2/ACS (rhBMP-2 at 1.5 mg/ml; 0.1 mg/defect) or served as sham-surgery controls. The flaps were adapted and sutured around the healing abutments leaving the implants in a transmucosal position. The animals were sacrificed at 16 weeks postsurgery and block sections of the implant sites were harvested and prepared for histometric analysis. RESULTS: One dental implant from each treatment group failed to osseointegrate. Another 3 dental implants (sham-surgery controls) failed to osseointegrate with newly-formed bone in the defect area. Thus, 7 of 8 defect sites (4/4 animals) receiving rhBMP-2/ACS compared to 4 of 8 sites (2/4 animals) receiving sham-surgery exhibited evidence of osseointegration with newly formed bone in the defect area. Mean +/- SD defect height amounted to 5.3 +/- 0.2 and 5.4 +/- 0.1 mm for the rhBMP-2/ACS and sham-surgery sites, respectively. Vertical bone gain in rhBMP-2/ACS treated defects (3.9 +/- 0.3 mm) did not differ significantly from that in the sham-surgery control (3.7 +/- 0.4 mm; P > 0.05; paired t-test, N = 4). There were also no significant differences noted for coronal bone-implant contact (3.0 +/- 0.6 versus 3.6 +/- 0.5 mm), and bone-implant contact within the defect site (28.5% +/- 15.1% versus 27.4% +/- 31.7%) and within resident bone (46.9% +/- 26.8% versus 47.8% +/- 39.4%) for the rhBMP-2/ACS and control sites, respectively. CONCLUSIONS: The observations in this study point to a substantial native osteogenic potential of the alveolar process that has previously not been explored and show that surgical reentry observations of new bone formation may not necessarily indicate that osseointegration has occurred. Bone formation in control defects was substantially greater than predicted, limiting the value of adding an osteoinductive biologic construct.     

Buccal Bone Formation After Flapless Extraction: A Randomized,Controlled Clinical Trial Comparing Recombinant Human Bone Morphogenetic Protein 2/Absorbable Collagen Carrier and Collagen Sponge Alone

Background: Flapless extraction of teeth allows for undisturbed preservation of the nearby periosteum and a source of osteoprogenitor cells. Recombinant human bone morphogenetic protein 2 (rhBMP‐2) has been used for different bone augmentation purposes with great osteoinductive capacity. The aim of this study is to compare the bone regenerative ability of rhBMP‐2 on an absorbable collagen sponge (ACS) carrier to a collagen sponge (CS) alone in extraction sites with ≥50% buccal dehiscence. Methods: Thirty‐nine patients requiring extraction of a hopeless tooth with ≥50% buccal dehiscence were enrolled. After flapless extraction and randomization, either rhBMP‐2/ACS carrier or CS alone was placed in the extraction site. After extraction, a baseline cone beam computed tomography (CBCT) scan was obtained of the site, and a similar scan was obtained 5 months postoperatively. Medical imaging and viewing software were used to compare the baseline and 5‐month postoperative images of the study site and assess ridge width measurements, vertical height changes, and buccal plate regeneration. Results: Radiographically, CBCT analysis showed that with ≥50% of buccal bone destruction, rhBMP‐2/ACS was able to regenerate a portion of the lost buccal plate, maintain theoretical ridge dimensions, and allow for implant placement 5 months after extraction. The test group performed significantly (P <0.05) better in regard to clinical buccal plate regeneration (4.75 versus 1.85 mm), clinical ridge width at 5 months (6.0 versus 4.62 mm), and radiographic ridge width at 3 mm from the alveolar crest (6.17 versus 4.48 mm) after molar exclusion. There was also significantly (P <0.05) less remaining buccal dehiscence, both clinically (6.81 versus 10.0 mm) and radiographically (3.42 versus 5.16 mm), at 5 months in the test group. Significantly (P <0.05) more implants were placed in the test group without the need for additional augmentation. The mean loss in vertical ridge height (lingual/palatal) was less in the test sites but was not significantly (P = 0.514) different between the test and control groups (0.39 versus 0.64 mm). Conclusions: rhBMP‐2/ACS compared to CS alone used in flapless extraction sites with a buccal dehiscence is able to regenerate lost buccal plate, maintain theoretical ridge dimensions, and allow for implant placement 5 months later.     

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.     

Regenerative potential and healing dynamics of the periodontium: a critical‐size supra‐alveolar periodontal defect study

Objectives: The nature and characteristics of the newly formed periodontium obtained following regenerative procedures remain a matter of controversy. The objective of this study was to evaluate the regenerative potential of the periodontal attachment and healing dynamics as observed from the spatial distribution of newly formed cementum, periodontal ligament (PDL) and alveolar bone following optimal circumstances for wound healing/regeneration in a discriminating animal model. Material and Methods: Critical‐size, 6‐mm, supra‐alveolar, periodontal defects were surgically created in six young adult Beagle dogs. Space‐providing ePTFE devices with 300‐μm laser‐drilled pores were implanted to support wound stability and space provision in one jaw quadrant/animal. Treatments were alternated between left and right jaw quadrants in subsequent animals. The gingival flaps were advanced to submerge the defect sites for primary intention healing. Histometric analysis followed an 8‐week healing interval. Results: Healing was uneventful in all animals. The histometric analysis showed that cementum regeneration (2.99 ± 0.22 mm) was significantly greater than PDL (2.54 ± 0.18 mm, p=0.03) and bone regeneration (2.46 ± 0.26 mm, p=0.03). The wound area showed significant positive non‐linear effect on cementum (log β=1.25, p<0.001), PDL (log β=1.24, p<0.001) and new bone formation (log β=1.36, p<0.001). A high degree of concordance and significant linear relationship was observed between cementum, PDL and bone regeneration indicating that their formation virtually occurred in parallel. Conclusions: Cementum, PDL and alveolar bone virtually regenerate in parallel under optimal circumstances for periodontal wound healing/regeneration. Moreover, space provision positively influences the extent of periodontal regeneration.     

Flapless Implant Surgery Using a Mini‐Incision

Background: Traditional flapless implant surgery using a soft tissue punch device requires a circumferential excision of keratinized tissue at the implant site. A new flapless implant technique that can submerge implant fixtures is needed. Purpose: This article describes a flapless implant surgery method using a mini‐incision and compares the effects of soft tissue punch and mini‐incision surgery on both the amount of osseointegration and the bone height around the implants using a canine mandible model. Materials and Methods: Bilateral, edentulated, flat alveolar ridges were created in the mandibles of six mongrel dogs. After a 3‐month healing period, two implants were placed on each side of the mandible using either soft tissue punch or mini‐incision procedures. After an additional 3‐month healing period, a second stage surgery and transmucosal abutment attachment was performed for mini‐incision implant cases. Following a 2‐month healing period, the dogs were sacrificed to evaluate the osseointegration and bone height around the implants. Results: Average bone height was 9.6 ± 0.4 mm in the soft tissue punch group and 9.8 ± 0.3 mm in the mini‐incision group (p > .05). Average osseointegration was 70.4 ± 6.3% in the soft tissue punch group and 71.2 ± 7.1% in the mini‐incision group (p > .05). No significant differences were noted between the two groups in vertical alveolar ridge height or bone/implant contact. Conclusions: Our findings support the clinical use of mini‐incision implant surgery at sites where implants need to be protected below the soft tissue during the early phase of healing, particularly for patients with poor bone quality and/or low primary implant stability.     

Deproteinized bovine bone mineral in marginal defects at implants installed immediately into extraction sockets: an experimental study in dogs

Aim: To evaluate the influence of deproteinized bovine bone mineral (DBBM) particles concomitant with the placement of a collagen membrane on alveolar ridge preservation and on osseointegration of implants placed into alveolar sockets immediately after tooth extraction. Material and methods: The pulp tissue of the mesial roots of ₃P₃ was removed in six Labrador dogs and the root canals were filled. Flaps were elevated in the right side of the mandible, and the buccal and lingual alveolar bony plates were exposed. The third premolar was hemi‐sectioned and the distal root was removed. A recipient site was prepared and an implant was placed lingually. After implant installation, defects of about 0.6 mm wide and 3.1 mm depth resulted at the buccal aspects of the implant, both at the test and at the control sites. The same surgical procedures and measurements were performed on the left side of the mandible. However, DBBM particles with a size of 0.25–1 mm were placed into the remaining defect concomitant with the placement of a collagen membrane. Results: All implants were integrated into mature bone. No residual DBBM particles were detected at the test sites after 4 months of healing. Both the test and the control sites showed buccal alveolar bone resorption, 1.8±1.1 and 2.1±1 mm, respectively. The most coronal bone‐to‐implant contact at the buccal aspect was 2±1.1 an 2.8±1.3 mm, at the test and the control sites, respectively. This difference in the distance was statistically significant. Conclusion: The application of DBBM concomitant with a collagen membrane to fill the marginal defects around implants placed into the alveolus immediately after tooth extraction contributed to improved bone regeneration in the defects. However, with regard to buccal bony crest preservation, a limited contribution of DBBM particles was achieved. To cite this article:
Caneva M, Botticelli D, Pantani F, Baffone GM, Rangel IG Jr, Lang NP. Deproteinized bovine bone mineral in marginal defects at implants installed immediately into extraction sockets: an experimental study in dogs.
Clin. Oral Impl. Res. 23 , 2012; 106–112.
doi: 10.1111/j.1600‐0501.2011.02202.x     

Which device is more accurate to determine the stability/mobility of dental implants? A human cadaver study

Summary Non‐invasive devices including resonance frequency (RF) analysis and mobility measuring (MM) damping capacity assessment are used to measure implant stability/mobility. The aims of the study were to compare the primary stability of implant inserted into extraction sockets by using RF with cable, RF wireless and new wireless MM device, to clarify the relation between these devices and to understand the correlations between peri‐implant bone levels and implant stability. A total of 30 screw‐type implants (3·75 × 11 and 4·2 × 11 mm) were inserted into extraction sockets of eight mandibular pre‐molar regions of human cadavers. The primary stability of implants was measured by three devices after insertion. Peri‐implant vertical defects were created in millimetre increments ranging between 0 and 5 mm, and stability/mobility of implants were analysed. At placement, the mean implant stability quotient of RF with cable, RF wireless and MM device values was 46 ± 1, 57·8 ± 9 and ?5·4 ± 1, respectively. Statistical correlations were demonstrated between these devices (P = 0·001). Statistically significant differences were presented for all peri‐implant detects ranging between 0 and 5 mm for RF with cable and RF wireless at all increments. However, only a significant decrease was found between 0 and 1 mm defects, and 4 and 5 mm defects in MM device. Although RF with cable and RF wireless seem to be suitable to detect peri‐implant bone loss around implants in 1 mm increments, the new MM device may not be suitable to detect the 1 mm peri‐implant bone changes in human dried cadaver mandibles.     

Implant-guided vertical bone growth in the mini-pig

Objective: To attain and describe guided vertical bone regeneration around titanium (Ti) and titanium zirconium (Ti–Zr) dental implants utilizing non‐glycosylated recombinant human bone morphogenetic protein‐2 (ng/rhBMP‐2), biomaterial scaffolds and a scaffold retainer. Materials and methods: Thirty‐two modified Straumann TE implants were partially embedded in the mandibles of eight adult mini‐pigs. Pre‐shaped resorbable scaffolds were placed around the implant and shielded and stabilized with a newly developed Ti custom scaffold retainer (umbrella) or wide‐neck (WN) healing caps to stabilize the scaffold. Ng/rhBMP‐2 (50 μg) was applied to the supracrestal portion of the implant or incorporated within the scaffold. At 9 weeks, soft tissue healing was assessed. Vertical bone regeneration outcomes including bone height, bone‐to‐implant contact (BIC) and bone volume were assessed by micro‐computed tomography and histology. Results: Soft tissue healing at the test sites (+ng/rhBMP‐2/+scaffold) appeared to be substantially better than the control sites (?ng/rhBMP‐2/?scaffold). Bone height, BIC percentage and bone volume were all similar regardless of whether WN healing caps or umbrella scaffold stabilization was used for all biomaterial scaffolds tested. WN healing cap test sites showed greater new bone height and BIC as compared with aggregate data from the control sites (P=0.05). Comparison of aggregate data from the umbrella test sites showed greater BIC and new bone volume as compared with aggregate data from the control sites(P=0.05). Conclusion: Vertical bone regeneration was successfully attained utilizing ng/rhBMP‐2, biomaterial scaffolds and a scaffold retainer.     

Microcomputed Tomographic Analysis of the Alveolar Ridge Alteration around Extraction Sites with and without Immediate Implants Placement: In Vivo Study

Background: The aim was to assess the alveolar ridge alteration around extraction sites with and without immediate implants according to extraction socket classification (ESC) using microcomputed tomography (micro‐CT). Material and Methods: Ten beagle dogs (mean age and weight: 24 ± 0.83 months and 13.8 ± 0.49 kg, respectively) were randomly divided into three groups according to the ESC. In Group 1 (ESC‐I), bilateral first and third premolars were extracted and replaced with immediate implants. In Group 2 (ESC‐II), two adjacent premolars were extracted with one immediate implant placement in the mesial socket in the maxilla and in the distal socket in the mandible. In Group 3 (ESC‐III), three adjacent teeth were extracted and an immediate implant was placed in the central socket. Primary closure was achieved using resorbable sutures. Buccal sites with dehiscence defects were excluded. After 4 months, subjects were sacrificed and alveolar ridge widths were measured at 1 mm interval in axial and sagittal views, using micro‐CT in sites with and without immediate implants. Results: In sites without immediate implant placement, alveolar ridge width was significantly higher in Group 1(6.1 ± 1.35 mm) than Group 3 (4.14 ± 1.53 mm) (p < .05). In sites with immediate implant placement, the alveolar ridge width was higher among sites in Group 1 (6.4 ± 3.8 mm) than Group 2 (4.8 ± 0.46 mm) (p < .05) and Group 3 (5.02 ± 0.84 mm) (p < .05). Overall, between each corresponding group in both sites with and without immediate implant placement at 1 mm thickness, there was no significant difference in the alveolar ridge widths. Conclusion: With the exception of Group 1 (ESC‐I), immediate implant placement did not prevent or minimize bone remodeling in extraction sites according to ESC.     

Peri-implant bone organization under immediate loading conditions: collagen fiber orientation and mineral density analyses in the minipig model

Background: Mechanical properties of bones are greatly influenced by percentages of organic and mineral constituents. Nevertheless, information about mineralization level on a microscopic scale and collagen fiber organization in peri‐implant bone after immediate loading is scarce. Purpose: The aim of this work was to analyze and compare the degree of mineralization and collagen fiber orientation in alveolar bone (AB) and peri‐implant bone of immediately loaded (IL) and unloaded (NL) implants. Materials and Methods: A total of 25 dental implants of 3.8 mm in diameter and 11 mm in length were used in the present study. In five minipigs, three premolars and the first molar were removed from the left side of the mandible. Three months later, five implants for each animal were inserted. Four implants were loaded immediately with a fixed restoration, while one implant was left unloaded. After a 4‐month healing period, all implants were retrieved. Circularly polarized light and scanning electron microscope with backscattered electron imaging were used to analyze both peri‐implant and AB retrieved 5 mm from the implant. Results: The bone/implant contact ratio (BIC %) was 77.8 ± 5.9% for the IL implants and 78.0 ± 5.8% for the NL implants; the difference was not statistically significant (p = 0.554). In the peri‐implant bone, the area related to transverse collagen fibers was 112,453 ± 4,605 pixels for IL implants and 87,256 ± 2,428 pixels for NL implants. In the AB, the area related to transverse collagen fibers was 172,340 ± 3,892 pixels. The difference between groups was statistically significant (p < .001). The degree of mineralization of peri‐implant bone was 137 ± 19 gray level for IL implants and 115 ± 24 gray level for NL implants, while in the AB, the degree of mineralization was 125 ± 26 gray level. This difference was statistically significant (p < .001). Conclusion: In this study, it was found that IL and NL implants showed the same degree of osseointegration. The bone matrix around IL implants had a higher quantity of transverse collagen fibers and presented a higher level of mineralization.