Alveolar ridge augmentation using implants coated with recombinant human growth/differentiation factor -5 (rhGDF-5). Radiographic observations.

OBJECTIVES: Application of growth factors onto dental implant surfaces is being considered to support local bone formation. Bone morphogenetic protein-2 (BMP-2) and BMP-7 have been shown to support local bone formation, but are also associated with adverse events including seroma formation, extensive bone remodeling, and implant displacement captured in the radiographic evaluation. This report presents mineralized tissue formation and associated adverse events following implantation of recombinant human growth/differentiation factor-5 (rhGDF-5) coated onto a purpose-designed titanium porous-oxide implant surface. MATERIAL AND METHODS: Twelve young adult Labrador dogs were used. Three 10-mm titanium implants/jaw quadrant were placed 5 mm into the alveolar ridge in the posterior mandible following surgical extraction of the premolar teeth and reduction of the alveolar ridge. Six animals received implants coated with rhGDF-5 at 30 or 60 µg/implant in contralateral jaw quadrants. Six animals received implants coated with rhGDF-5 at 120 µg/implant or uncoated implants (sham-surgery control) using the same split-mouth design. The mucoperiosteal flaps were advanced, adapted, and sutured to submerge the implants. Radiographic recordings were made immediately postsurgery (baseline), and at week 4 and 8 (end of study). Two masked examiners performed the analysis using computer enhanced radiographic images. RESULTS: rhGDF-5 coated implants displayed mineralized tissue formation significantly exceeding that of the sham-surgery control in a dose-dependent order. The greatest increase was observed for implants coated with rhGDF-5 at 60 µg and 120 µg amounting to approximately 2.2 mm for both groups at 8 weeks. Importantly, none of the implants showed evidence of peri-implant bone remodeling, implant displacement, or seroma formation. The newly formed mineralized tissues assumed characteristics of the resident bone. CONCLUSIONS: rhGDF-5 coated onto a titanium porous-oxide implant surface exhibits a dose-dependent potential to stimulate local mineralized tissue formation. Application of rhGDF-5 appears safe as it is associated with limited, if any, adverse events.

Alveolar ridge augmentation using implants coated with recombinant human growth/differentiation factor-5: histologic observations.

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 microg rhGDF-5, and six animals received implants coated with 120 microg 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 microg rhGDF-5 versus 1.2+/-0.5, 1.2+/-0.6, and 0.6+/-0.2 mm for implants coated with 60 microg rhGDF-5, 30 microg 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 microg dose exhibiting more advanced remodelling than the 60 and 30 microg 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.

Alveolar ridge augmentation using implants coated with recombinant human bone morphogenetic protein-7 (rhBMP-7/rhOP-1): histological observations.

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 mm(2); 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.

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-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 mm(2), 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.

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.

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.

Histological and biomechanical evaluation of phosphorylcholine-coated titanium implants.

OBJECTIVE: Compounds considered for drug delivery from oral implant surfaces in support of local bone formation might themselves influence osseointegration. Phosphorylcholine (PC) polymers have been shown to enhance the biocompatibility of medical devices and to serve as drug delivery systems. The objective of this study was to evaluate local bone formation and osseointegration at PC and positively charged PC (PC+)-coated endosseous implants in an established rabbit model. MATERIAL AND METHODS: Sixteen adult female New Zealand White rabbits were used. Eight animals received PC-coated and control titanium porous oxide surface implants placed in the left and right distal femural condyle (trabecular bone) and proximal tibial metaphysis (cortical bone) using aseptic routines. The remaining eight animals similarly received PC+ and control implants. One implant was placed in each femural condyle and two implants in each tibial metaphysis. Experimental and control implants were alternated between the left and right hind legs. Fascia and skin were closed in layers. The animals were euthanized following a 6-week healing interval for biomechanical (removal torque) and histometric analyses. RESULTS: Peri-implant bone density was considerably greater at tibial compared with femoral sites within as well as immediately outside the implant threads. However, there were no significant differences in bone density among PC, PC+, and control implants. Nevertheless, bone-implant contact was significantly lower at PC compared with PC+ and control implants in cortical bone (p<0.05). Numerical differences in trabecular bone did not reach statistical significance. The removal torque evaluation revealed significantly lower values for PC compared with PC+ and control sites (p<0.05). CONCLUSION: The histometric and biomechanical analyses suggest that PC coating may influence biological processes and ultimately osseointegration of endosseous implants. Apparently, incorporation of cationic charges may reverse or compensate for this scenario. Nevertheless, both PC coatings exhibited clinically acceptable osseointegration. In perspective, PC technology appears to be a viable candidate delivery system for agents in support of local bone formation at endosseous implant surfaces.

Bone healing dynamics at buccal peri-implant sites.

BACKGROUND: It is common belief that immediate implant placement into extraction sites may act to preserve the alveolar process. The objective of this study was to evaluate healing dynamics at buccal peri-implant sites in relation to the dimensions of the alveolar ridge. METHODS: Bilateral, critical-size, supraalveolar, peri-implant defects were created in 12 male Hound Labrador mongrel dogs following surgical horizontal cut-down of the alveolar ridge. Each jaw quadrant received three 10-mm titanium implants placed 5 mm into extraction sites of the third and fourth premolar teeth leaving 5 mm in a supraalveolar position. The mucoperiosteal flaps were advanced, adapted, and sutured for primary intention healing. Bone fluorescent markers were administered at weeks 3 and 4 postsurgery, and pre-euthanasia. Incandescent, polarized, and fluorescent light microscopies were used to assess the width of the buccal wall of the alveolar ridge and local bone remodeling over the 8-week healing interval. RESULTS: There was a significant association between the width of the buccal alveolar ridge and extent of bone resorption evaluated by incandescent and fluorescent light microscopy. A non-linear association was observed between the buccal ridge width and resorption of the alveolar ridge. A 2-mm threshold was established to account for this non-linearity. The strength of this association was two times greater in specimens with a buccal ridge width <2 mm compared with a wider ridge (beta=1.62 vs. 0.80) observed by fluorescent light microscopy. Accordingly, mean buccal resorption was significantly greater when the ridge width was <2 mm. Fluorescent light microscopy consistently showed greater buccal resorption compared with incandescent light microscopy (P<0.05). Agreement between the examination techniques was low (concordance correlation coefficient=0.49), especially for higher values of buccal resorption. CONCLUSION: When implants are placed into extraction sites, proximity to the buccal alveolar crest appears a major consideration. The observations herein suggest that the width of the buccal alveolar ridge should be at least 2 mm to maintain the alveolar bone level. These observations likely have general implications for implant placement using most surgical protocols.

Bone morphogenetic proteins: a realistic alternative to bone grafting for alveolar reconstruction.

Preclinical studies have shown that rhBMP-2 induces normal physiologic bone in clinically relevant defects in the craniofacial skeleton. The newly formed bone assumes characteristics of the adjacent resident bone and allows placement, osseointegration/re-osseointegration, and functional loading of endosseous implants. Clinical studies optimizing dose, delivery technologies, and conditions for stimulation of bone growth will bring about a new era in dentistry. The ability to predictably promote osteogenesis through the use of bone morphogenetic protein technologies is not far from becoming a clinical reality and will have an astounding effect on how dentistry is practiced.

Surface-etching enhances titanium implant osseointegration in newly formed (rhBMP-2-induced) and native bone.

PURPOSE: The influence of surface modifications on osseointegration in newly formed bone is not well established. The purpose of this study was to compare osseointegration at acid-etched versus turned implants in newly formed and native bone. METHODS: Supra-alveolar peri-implant defects were created in 8 hound/Labrador mongrel dogs. Titanium implants 10 mm long (2 turned and 1 dual acid-etched) were placed 5 mm into the surgically reduced alveolar crest, creating 5-mm supra-alveolar peri-implant defects. Recombinant human bone morphogenetic protein-2 (rhBMP-2; 0.4 mg) in a collagen carrier was used to induce new bone formation. A macroporous, expanded polytetrafluoroethylene device was used to delineate new bone formation. The animals were euthanized at 8 weeks for histometric analysis of the experimental sites. RESULTS: There were no significant differences in rhBMP-2-induced bone density (mean +/- SD) at acid-etched versus turned implants (20.6% +/- 5.3% vs 23.8% +/- 4.7%; P = .232). However, there was a significant difference in bone-implant contact in favor of the acid-etched implants (12.3% +/- 6.8% vs 7.9% +/- 3.1%; P = .05). Native bone density averaged 63.9% +/- 7.5% and 64.5% +/- 9.0% for acid-etched and turned implants, respectively (P = .641). Nevertheless, bone-implant contact was significantly enhanced at acid-etched versus turned implants (59.7% +/- 11.3% vs 40.7% +/-21.2%; P =.005). CONCLUSIONS: Surface dual acid-etching of titanium implants has a positive effect on osseointegration in newly formed and native bone. Significant differences in bone density do not appear to influence this effect.

Histologic evaluation of implants following flapless and flapped surgery: a study in canines.

BACKGROUND: Flapless surgery requires penetration of the alveolar mucosa and bone without reflection of mucoperiosteal flaps. Do these techniques force gingival tissue or foreign materials into osteotomies? If so, do such tissues or materials interfere with osseointegration? A proof-of-principle study using a canine model attempted to answer these questions. METHODS: Five young adult Hound Labrador mongrel dogs received implants with a moderately roughened surface by anodic oxidation using flapless or conventional one-stage (control) surgery in contralateral jaw quadrants. The implants were placed into the osteotomies, and the international stability quotient (ISQ) was recorded using resonance frequency analysis. These measurements were repeated following a 3-month healing interval when the animals were euthanized, and implants and surrounding tissues were retrieved and processed for histologic analysis. RESULTS: The implants were stable upon insertion and demonstrated increased stability at 3 months without significant differences between surgical protocols. The histologic evaluation showed high bone-implant contact (flapless surgery: 54.7% +/- 8.4%; control: 52.2% +/- 13.0%; P >0.05) without evidence of gingival tissue or foreign body inclusions. There were no significant differences in marginal bone levels between the surgical protocols. Post-insertion and at 3 months, ISQ values depended on the amount of torque delivered. Immediately post-insertion, for every 1-unit increase in torque value, the ISQ increased by 0.3 (95% confidence interval: 0.1 to 0.4; P = 0.0043). Three months postoperatively, for every one-unit increase in torque the ISQ value decreased 0.2 (95% confidence interval: -0.4 to -0.1; P = 0.0012). The effect of torque on ISQ values was independent of treatment effects and remained significant after adjustment for treatment. CONCLUSIONS: The results suggest that implants placed without flap reflection remain stable and exhibit clinically relevant osseointegration similar to when implants are placed with flapped procedures. Greater torque at implant placement resulted in less implant stability at 3 months.

The critical-size supraalveolar peri-implant defect model: characteristics and use.

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, phi 4.0 x 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.

Bone-implant contact at calcium phosphate-coated and porous titanium oxide (TiUnite)-modified oral implants.

BACKGROUND: Calcium phosphate (CP)-coated implants are usually referred to as having osteoconductive properties, whereas titanium implants with a native oxide layer are considered less osteoconductive. Often smooth titanium oxides (TOs) are compared to relatively rough CP structures. The objective of this study was to evaluate osteoconduction by comparing bone-implant contact at a relatively smooth, highly crystalline CP coating with a structured, porous TO (TiUnite)-modified surface. MATERIAL AND METHODS: Ten adult Hound Labrador mongrel dogs were used. Four titanium implants (Nobel Biocare) with CP-coated (2) or TO-modified (2) surfaces were installed 12 weeks following mandibular premolar and molar teeth extraction. The implants were alternated within and between jaw quadrants in consecutive animals. Mucosal flaps were advanced and sutured leaving the implants in a submerged position. The animals were injected with fluorescent bone labels at 3 and 4 weeks postsurgery, and pre-euthanasia to monitor progress of bone formation. The animals were euthanized at 8 weeks postsurgery and block biopsies were prepared for histologic and histometric analysis. RESULTS: There were no remarkable differences in bone formation and apparent bone-implant contact comparing the TO-modified and CP-coated surfaces. However, the measured average bone-implant contact was 71% and 57% (P=0.027) for TO-modified and CP-coated implants, respectively. CONCLUSIONS: We conclude that the TO surface exhibits osteoconductive properties exceeding that of the CP surface. One or several of the chemical and physical properties of the TO surface may result in the remarkable bone formation along its surface. This study indicated that crystallinity and/or chemistry may be important.

Tissue engineering with recombinant human bone morphogenetic protein-2 for alveolar augmentation and oral implant osseointegration: experimental observations and clinical perspectives.

Surgical placement of oral implants is governed by the prosthetic design and by the morphology and quality of the alveolar bone. Nevertheless implant placement often appears difficult, if at all possible, due to aberrations of the alveolar ridge. Hence prosthetically dictated implant positioning often entails augmentation of the alveolar ridge and adjoining structures. In this review we discuss recent observations of the biologic potential, clinical relevance, and perspectives of application of recombinant human bone morphogenetic protein-2 (rhBMP-2) technologies for alveolar bone augmentation and oral implant osseointegration. Using discriminating critical-size supraalveolar defects and clinical modeling in dogs, we show that rhBMP-2 has a substantial potential for augmenting alveolar bone and supporting osseointegration of titanium oral implants. Moreover, using clinical modeling, we demonstrate re-osseointegration in advanced periimplantitis defects and long-term functional loading of titanium oral implants placed into rhBMP-2-induced bone. Our studies suggest that inclusion of rhBMP-2 for alveolar bone augmentation and oral implant fixation will not only enhance the predictability of existing clinical protocol but also allow new approaches to these procedures.

Periodontal repair in dogs: guided tissue regeneration enhances bone formation in sites implanted with a coral-derived calcium carbonate biomaterial.

BACKGROUND: Previous studies suggest that a bioresorbable calcium carbonate coral implant (CI) supports space provision and bone formation for guided tissue regeneration (GTR). However, it could not be discerned whether observed effects were because of GTR or whether the CI possessed osteoconductive properties enhancing bone formation. The objective of this study was to evaluate bone formation associated with the CI biomaterial in the presence and absence of provisions for GTR. METHODS: Routine, critical size, 6 mm, supra-alveolar periodontal defects were created in 12 young adult Beagle dogs. Five animals received the CI alone (Biocoral 1000). Seven animals received the CI/GTR combination using an expanded polytetrafluoroethylene barrier (GORE-TEX Regenerative Material). The animals were euthanized at 4 weeks postsurgery and tissue blocks of the experimental sites were collected and processed for histometric analysis. RESULTS: Clinical healing was uneventful. The histopathologic and histometric analysis revealed significantly increased bone formation (height and area) in sites receiving the CI/GTR combination compared with CI alone (2.3+/-0.6 versus 1.2+/-0.9 mm; and 3.1+/-0.8 versus 1.2+/-1.1 mm2; p<0.05). The CI biomaterial appeared to be mostly unassociated with new bone formation; the CI particles were observed sequestered in newly formed bone, fibrovascular marrow, and in the supra-alveolar connective tissue. Cementum formation was limited and observed in few sites for both treatment protocols. CONCLUSION: While GTR promoted new bone formation, the CI contributed limited, if any, osteoconductive effects.

Prognostic factors for alveolar regeneration: bone formation at teeth and titanium implants.

OBJECTIVES: There is a limited understanding of the effect of defect characteristics on alveolar bone healing. The objectives of this study were to assess the effect of alveolar bone width and space provision on bone regeneration at teeth and titanium implants, and to test the hypothesis that the regenerative potentials at teeth and implants are not significantly different. METHODS: Critical size, 5-6-mm, supra-alveolar, periodontal defects were surgically created in 10 young adult dogs. Similarly, critical size, 5-mm, supra-alveolar, peri-implant defects were created in four dogs. A space-providing expanded polytetrafluoroethylene device was implanted for guided tissue regeneration/guided bone regeneration. The animals were euthanized at 8 weeks postsurgery. Histometric analysis assessed alveolar bone regeneration (height) relative to space provision by the device and the width of the alveolar crest at the base of the defect. Statistical analysis used the linear mixed models. RESULTS: A significant correlation was found between bone width and wound area (r=0.55892, p<0.0001). Generally, bone width and wound area had statistically significant effects on the extent of bone regeneration (p<0.0005 and p<0.0001, respectively). Bone regeneration was linearly correlated with the bone width at periodontal (p<0.001) and implant (p=0.04) sites, and with the wound area at periodontal (p<0.0001) and implant (p=0.03) sites. The relationships of bone regeneration with these two variables were not significantly different between teeth and implants (bone width: p=0.83; wound area: p=0.09). When adjusted for wound area, bone regeneration was significantly greater at periodontal than at implant sites (p=0.047). CONCLUSIONS: The horizontal dimension of the alveolar bone influences space provision. Space provision and horizontal dimension of the alveolar bone appear to be important determinants of bone regeneration at teeth and implants. The extent of alveolar bone formation at implant sites is limited compared with that at periodontal sites.

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.