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Abstract: Background: Recombinant human bone morphogenetic protein‐2 in an absorbable collagen sponge carrier (rhBMP‐2/ACS) has been shown to support significant bone formation when used to augment the maxillary sinus for implant dentistry. Nevertheless, bone biomaterials have been suggested to extend rhBMP‐2/ACS with limited support of the merits of such approaches. Objectives: To evaluate local bone formation/dental implant osseointegration following implantation of rhBMP‐2/ACS combined with a ceramic bone biomaterial using a mini‐pig sinus augmentation model. Methods: Twelve adult Göttingen mini‐pigs received rhBMP‐2/ACS (rhBMP‐2 adjusted to 0.43 mg/cc) alone or combined with an off‐the‐shelf biphasic ceramic (15%/85% HA/ß‐TCP) biomaterial at 3:1, 1:1 and 1:3 ratios randomized to contra‐lateral maxillary sinus sites yielding rhBMP‐2/ACS fractions of 100%, 75%, 50% and 25%, respectively. A 4‐cc implant volume was used for all sites. Two threaded dental implants (ø4.0 × 11.5 mm) were placed at each site. The animals were euthanized at 8 weeks for histologic analysis. Results: Surgical execution and healing were generally uneventful, infraorbital local swelling was observed in all animals until suture removal. rhBMP‐2/ACS combined with the ceramic biomaterial did not significantly enhance local bone formation (range 9.0 ± 1.5 to 9.7 ± 2.1 mm) compared with rhBMP‐2/ACS alone (8.6 ± 1.1 mm; p > 0.05). Variations in rhBMP‐2/ACS to ceramic matrix ratios yielding rhBMP‐2 doses approximating 0.4, 0.9, 1.3 and 1.7 mg/sinus did not appreciably influence bone formation/osseointegration. Conclusions: Whereas rhBMP‐2/ACS supports significant bone formation/osseointegration in the mini‐pig sinus augmentation model and thus appears an effective alternative for sinus augmentation procedures, adding a ceramic biomaterial to rhBMP‐2/ACS does not produce meaningful biological advantages. [ABSTRACT FROM AUTHOR]

Background Present clinical practice broadly relies on off-the-shelf allogeneic, xenogeneic or synthetic bone biomaterials in support of sinus augmentation. Also, recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge carrier (rhBMP-2/ACS) has been shown to support clinically relevant bone formation when used to augment the maxillary sinus. Objectives To evaluate local bone formation/dental implant osseointegration following implantation of two particulate bone biomaterials using the mini-pig sinus augmentation model. Methods Nine adult Göttingen mini-pigs were used for evaluation of a biphasic ceramic (15%/85% HA/ß-TCP) and an allogeneic mineralized bone biomaterial. Treatments randomized to contralateral sinus sites included sham-surgery (control) and biomaterials. Two threaded dental implants (ø4.0 × 11.5 mm) were placed at each sinus site. The animals were euthanized at 8 weeks for histologic analysis. Results Execution of the surgical protocol and healing was unremarkable. Limited infraorbital swelling was observed until suture removal. The biphasic ceramic and allogeneic bone biomaterials produced significantly increased bone formation (5.2 ± 1.9 mm and 4.9 ± 1.6 mm vs. 2.6 ± 0.5 mm, p < 0.05) and osseointegration (18.0 ± 6.0% and 25.1 ± 18.2% vs. 10.1 ± 8.0%, p < 0.05) over the sham-surgery control. No significant differences were observed between biomaterials. Conclusions Implantation of biphasic ceramic or allogeneic bone biomaterials enhances bone formation in the mini-pig maxillary sinus, however, dental implant bone support is incomplete resulting in overall limited osseointegration. [ABSTRACT FROM AUTHOR]

Background Previous studies document the therapeutic potential of recombinant human bone morphogenetic protein-2 (rh BMP-2) in an absorbable collagen sponge ( ACS) carrier for indications in the axial and appendicular skeleton. Nevertheless, the ACS does not comprise structural integrity to adequately support bone formation for onlay indications. The objective of this study was to evaluate local bone formation and osseointegration following surgical implantation of rh BMP-2 soak-loaded onto a compression resistant matrix ( CRM). Methods Routine, contralateral, critical-size, supraalveolar, peri-implant defects in five adult male Hound Labrador mongrel dogs received 0.8 mg rh BMP-2 soak-loaded onto either the ACS (benchmark control) or a CRM (collagen/ β- TCP/hydroxyapatite) followed by submerged wound closure for primary intention healing. The animals were euthanized at 8 weeks for histologic/histometric evaluation. Results Healing was uneventful albeit considerable initial swelling was observed for either treatment. Sites receiving rh BMP-2/ CRM showed significantly increased bone area (20.0 ± 0.9 versus 12.3 ± 2.6 mm2, p = 0.03) and bone density (24.1 ± 1.4% versus 14.6 ± 2.0%, p = 0.04) compared with those receiving rh BMP-2/ ACS. There were no significant differences between treatments for new bone height and osseointegration. Woven and lamellar trabecular bone lined with abundant osteoid was observed for all sites. Inconsistent cortex formation confirmed the immature nature of the newly formed bone. Seroma formation was observed for both treatments (80-100% of the animals/implants). Sites receiving rh BMP-2/ CRM showed residual ceramic granules undergoing biodegradation, including accumulation of foamy macrophages. Conclusions rh BMP-2/ CRM supports bone formation of clinically relevant geometry. Longer observation intervals as well as dose variations appear necessary to capture maturation of the newly formed bone, elimination of residual ceramic granules and resolution of seroma formation(s). [ABSTRACT FROM AUTHOR]

Aim: To compare the effect of timing of implant placement and guided bone regeneration (GBR) procedure on osseointegration and newly formed bone at 8 and 16 months. Material and Methods: In seven dogs, four different sites were bilaterally established: (1) an implant placed in a 6-month healed (6m-GBR) bovine bone mineral (BBM) grafted site; (2) a simultaneously placed implant with the grafted BBM (Si-GBR) followed by a membrane coverage; (3) an implant placed in a membraneprotected non-grafted defect; and (4) an implant placement in a naturally healed site (Cont). Histomorphometry was obtained at 8 and 16 months post-implant placement. Bone-implant contact (BIC), crestal bone resorption (CBR), vertical intra-bony (VIB) defect, bone (BAF) and particle (PAF) area fractions, and osteoconductivity (CON) levels were measured. Results: In all sites, BIC ranged between 62% and 79% with no significant differences. PAF ranged from 17% to 27%, with no effect of time. At 8 and 16 months, BAF was significantly smaller at the Si-GBR site when compared with all other sites, CON was significantly greater at the 6m-GBR site, and CBR and VIB were significantly smaller at the 6m-GBR when compared with the Si-GBR sites. Conclusions: The simultaneous and delayed techniques both showed a similar osseointegration level over time. However, the staged approach showed enhanced newly formed bone, higher osteoconduction around the grafted mineral, less CBR, and smaller vertical bone defect over time compared with the combined approach. [ABSTRACT FROM AUTHOR]

Polimeni G, Wikesjö UME, Susin C, Qahash M, Shanaman RH, Prasad HS, Rohrer MD, Hall J. Alveolar ridge augmentation using implants coated with recombinant human growth/differentiation factor-5: histologic observations. J Clin Periodontol 2010; 37: 759-768 doi: . Objectives: In vitro and in vivo preclinical studies suggest that growth/differentiation factor-5 (GDF-5) may induce local bone formation. The objective of this study was to evaluate the potential of recombinant human GDF-5 (rhGDF-5) coated onto an oral implant with a purpose-designed titanium porous oxide surface to stimulate local bone formation including osseointegration and vertical augmentation of the alveolar ridge. Materials and Methods: Bilateral, critical-size, 5 mm, supraalveolar peri-implant defects were created in 12 young adult Hound Labrador mongrel dogs. Six animals received implants coated with 30 or 60 μg rhGDF-5, and six animals received implants coated with 120 μg rhGDF-5 or left uncoated (control). Treatments were alternated 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: The clinical examination showed no noteworthy differences between implants coated with rhGDF-5. The cover screw and implant body were visible/palpable through the alveolar mucosa for both rhGDF-5-coated and control implants. There was a small increase in induced bone height for implants coated with rhGDF-5 compared with the control, induced bone height averaging (±SD) 1.6±0.6 mm for implants coated with 120 μg rhGDF-5 versus 1.2±0.5, 1.2±0.6, and 0.6±0.2 mm for implants coated with 60 μg rhGDF-5, 30 μg rhGDF-5, or left uncoated, respectively ( p<0.05). Bone formation was predominant at the lingual aspect of the implants. Narrow yellow and orange fluorescent markers throughout the newly formed bone indicate relatively slow new bone formation within 3–4 weeks. Implants coated with rhGDF-5 displayed limited peri-implant bone remodelling in the resident bone; the 120 μg dose exhibiting more advanced remodelling than the 60 and 30 μg doses. All treatment groups exhibited clinically relevant osseointegration. Conclusions: rhGDF-5-coated oral implants display a dose-dependent osteoinductive and/or osteoconductive effect, bone formation apparently benefiting from local factors. Application of rhGDF-5 appears to be safe as it is associated with limited, if any, adverse effects. [ABSTRACT FROM AUTHOR]

Susin C, Qahash M, Polimeni G, Lu PH, Prasad HS, Rohrer MD, Hall J, Wikesjö UME. Alveolar ridge augmentation using implants coated with recombinant human bone morphogenetic protein-7 (rhBMP-7/rhOP-1): histological observations. J Clin Periodontol 2010; 37: 574–581. doi: 10.1111/j.1600-051X.2010.01554.x. Background: Pre-clinical studies have shown that recombinant human bone morphogenetic protein-2 (rhBMP-2) coated onto purpose-designed titanium porous-oxide surface implants induces clinically relevant bone formation and osseointegration. The objective of this study was to examine the potential of rhBMP-7, also known as recombinant human osteogenic protein-1 (rhOP-1), coated onto titanium porous-oxide surface implants to support vertical alveolar ridge augmentation and implant osseointegration. Materials and Methods: Bilateral, critical-size, 5 mm, supraalveolar peri-implant defects were created in six young adult Hound Labrador mongrel dogs. The animals received implants coated with rhBMP-7 at 1.5 or 3.0 mg/ml randomized to contra-lateral 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 3, 4, 7, and 8 weeks post-surgery when they were euthanized for histological evaluation. Results: Without striking differences between treatments, the implant sites exhibited a swelling that gradually regressed to become hard to palpation disguising the implant contours. The histological evaluation showed robust bone formation; the newly formed bone assuming characteristics of the contiguous resident bone, bone formation (height and area) averaging 4.1±1.0 versus 3.6±1.7 mm and 3.6±1.9 versus 3.1±1.8 mm2; and bone density 56% versus 50% for implants coated with rhBMP-7 at 1.5 and 3.0 mg/ml, respectively. Both treatments exhibited clinically relevant osseointegration, the corresponding bone–implant contact values averaging 51% and 47%. Notable peri-implant resident bone remodelling was observed for implants coated with rhBMP-7 at 3.0 mg/ml. Conclusions: rhBMP-7 coated onto titanium porous-oxide surface implants induces clinically relevant local bone formation including osseointegration and vertical augmentation of the alveolar ridge, the higher concentration/dose associated with some local side effects. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Novel implant technologies and reconstructive therapies for alveolar augmentation require pre-clinical evaluation to estimate their biologic potential, efficacy, and safety before clinical application. The objective of this report is to present characteristics and use of the critical-size, supraalveolar, peri-implant defect model. Methods: Bilateral extraction of the mandibular premolars was performed in 12 Hound Labrador mongrel dogs following horizontal surgical cut-down of the alveolar ridge approximating 6 mm. Each jaw quadrant received three custom-produced TiUnite™, ∅4.0 × 10 mm threaded implants placed into osteotomies prepared into the extraction sites of the third and fourth premolars. The implants exhibited a reference notch 5 mm from the implant platform to facilitate surgical placement leaving 5 mm of the implant in a supraalveolar position, and to serve as a reference point in the radiographic, histologic and histometric analysis. The implants were submerged under the mucoperiosteal flaps for primary intention healing. Fluorescent bone markers were administered at weeks 3 and 4 post-surgery, and pre-euthanasia. The animals were euthanized following an 8-week healing interval when block biopsies were collected for analysis. Results: Healing was generally uneventful. The radiographic and histometric evaluations demonstrate the limited osteogenic potential of this defect model. Whereas lingual peri-implant sites exhibited a mean (±SE) bone gain of 0.4±0.1 mm, resorption of the buccal crestal plate resulted in a mean bone loss of 0.4±0.2 mm for an overall osteogenic potential following sham-surgery averaging 0.0±0.1 mm. Overall bone density and bone–implant contact in the contiguous resident bone averaged 79.1±1.1% and 76.9±2.3%, respectively. Conclusion: The results suggest that the critical-size, supraalveolar, peri-implant defect model appears a rigorous tool in the evaluation of candidate technologies for alveolar reconstruction and osseointegration of endosseous oral implants. Limited innate osteogenic potential allows critical evaluation of osteogenic, osteoconductive, or osteoinductive technologies in a challenging clinical setting. [ABSTRACT FROM AUTHOR]