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.     

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.     

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.     

Bone apposition to titanium implants biocoated with recombinant human bone morphogenetic protein 2 (rhBMP-2). A pilot study in dogs

The aim of the present study was to investigate bone formation to recombinant human bone morphogenetic protein-2 (rhBMP-2)-biocoated and rhBMP-2-nonbiocoated titanium implants after implantation in dogs. Implantation of sand-blasted and acid-etched (C), chromosulfuric acid surface-enhanced (CSA), and rhBMP-2-biocoated CSA [BMP-A: noncovalently immobilized rhBMP-2 (596 ng/cm²), BMP-B: covalently immobilized rhBMP-2 (819 ng/cm²)] implants was performed in both the mandible and tibia of dogs. After 4 weeks of healing, the percentage of direct bone to implant contact (BIC) and the induced bone density (BD) at a distance of less than and greater than 1 mm adjacent to each implant was assessed. Histomorphometric analysis of implants inserted in the mandible and tibia revealed that BIC values appeared to be highest in the BMP-B group, followed by BMP-A, CSA, and C. BD as measured at a distance of <1 mm revealed obvious differences between groups: BMP-B>BMP-A>CSA>C. However, no differences between groups were observed at a distance of >1 mm. Within the limits of the present study, it may be concluded that rhBMP-2 immobilized by covalent and noncovalent methods on CSA-treated implant surfaces seemed to be stable and promoted direct bone apposition in a concentration-dependant manner.An erratum to this article can be found at     

Effect of recombinant human bone morphogenetic protein-4 dose on bone formation in a rat calvarial defect model

BACKGROUND: Bone morphogenetic proteins (BMPs) are being evaluated for periodontal and bone regenerative therapy. The objective of this study was to evaluate the effect of recombinant human bone morphogenetic protein-4 (rhBMP-4) dose on local bone formation in a rat calvaria defect model. METHODS: Calvarial, 8 mm diameter, critical-size osteotomy defects were created in 140 male Sprague-Dawley rats. Seven groups of 20 animals each received either 1) rhBMP-4 (2.5 microg) in an absorbable collagen sponge (ACS) carrier, 2) rhBMP-4 (5 microg)/ACS, 3) rhBMP-4 (2.5 microg) in a beta-tricalcium phosphate (beta-TCP) carrier, 4) rhBMP-4 (5 microg)/beta-TCP, 5) ACS or 6) beta-TCP carrier controls, or 7) a sham-surgery control, and were evaluated by histologic and histometric parameters following a 2- or 8-week healing interval (10 animals/group/healing interval). RESULTS: Surgical implantation of rhBMP-4/ACS and rhBMP-4/beta-TCP resulted in enhanced local bone formation at both 2 and 8 weeks. Within the dose range examined, rhBMP-4 did not exhibit an appreciable dose-dependent response. Defect closure was not significantly different between the rhBMP-4/ACS and rhBMP-4/beta-TCP groups. New bone area of the rhBMP-4/ beta-TCP group was significantly greater than that of the rhBMP-4/ ACS group; however, bone density in the rhBMP-4/ACS group was significantly greater than that in the rhBMP-4/beta-TCP group at 8 weeks (P < 0.05). CONCLUSIONS: rhBMP-4 combined with ACS or beta-TCP has a significant potential to induce bone formation in the rat calvaria defect model. Within the selected rhBMP-4 dose range and observation interval, there appeared to be no meaningful differences in bone formation.     

Effect of recombinant human bone morphogenetic protein-2 on bone regeneration and osseointegration of dental implants

Recombinant human bone morphogenetic protein-2 (rhBMP-2) induced bone regeneration and osseointegration was evaluated in bony defects created within the hollow chamber of endosseous dental implants in 14 foxhound dogs. Bilateral extractions of mandibular premolars were performed and surgical implantation of 104 hollow cylinder implants followed after 8 weeks of healing. Experimental implants had their hollow chamber filled with 20 microg of rhBMP-2 delivered with a bovine collagen carrier, whereas the control implants had their apical chamber left empty. Dogs were followed for 2, 4, 8 and 12 weeks. Histomorphometric evaluation and immunohistochemical analysis were performed. Minimal bone was regenerated at 2 weeks for both groups. At 4 weeks, bone fill averaged 23.48% for the rhBMP-2 and 5.98% for the control group (P<0.05). At 8 weeks, mean bone fill was 20.94% and 7.75% for the rhBMP-2 and the controls, respectively (P<0.05). At 12 weeks, mean bone fill was 31.39% and 24.31% for the rhBMP-2 and control implants, respectively (P>0.05). Bone-implant contact (BIC) increased for both groups over time and at 8 weeks the rhBMP-2 BIC value was 18.65% and for the control 7.22% (P<0.05). At 12 weeks, the BIC was 43.78% and 21.05% for the rhBMP-2 and the control group, respectively (P<0.05). Immunohistochemical staining for type II collagen was positive only for parts of the collagen carrier and formation of cartilaginous intermediate was not observed in any of the specimens. The results suggest that, in confined defects adjacent to dental implants, rhBMP-2 can induce bone regeneration in close apposition to the implant surface.     

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.     

Bone formation at titanium porous oxide (TiUnite) oral implants in type IV bone

BACKGROUND: Several oral implant design advances have been suggested to overcome poor bone quality, an impediment for successful implant treatment. A novel titanium porous oxide (TPO) surface has been shown to offer favorable results in several settings. The objective of this study was to evaluate the local bone formation and osseointegration at TPO-modified implants in type IV bone. METHOD: Three TPO surface-modified implants (TiUnite) were installed into the edentulated posterior maxilla in each of 8 Cynomolgus monkeys. The animals were injected with fluorescent bone labels at 2, 3, 4 and 16 weeks post-surgery and were euthanized at week 16 when block biopsies were collected for histologic analysis. RESULTS: The predominant observation of the TPO implant surface was a thin layer of new bone covering most of the implant threads. Mean (+/-SE) bone-implant contact for the whole study group was 74.1 +/- 4.8%. There was a significant variability in bone-implant contact between animals (P = 0.0003) and between sites of the same animal (P < 0.0001). The variance in bone-implant contact was 30% larger among sites of the same animal than between different animals (187.5 vs. 144.8, respectively). There was a small but significant difference in bone density immediately outside, compared to within the threaded area of the implants (37.1 +/- 3.2% vs. 32.1 +/- 3.2%, P < 0.0001). Bone density outside the implant threads was significantly correlated (beta = 0.682, P < 0.0001) with the bone density within the threaded area. Bone density within the threaded area was significantly correlated (beta = 0.493, P = 0.0002) with bone-implant contact, whereas bone density outside the implant threads did not have a significant effect (beta = 0.232, P = 0.1). CONCLUSIONS: The results suggest that the TPO surface possesses a considerable osteoconductive potential promoting a high level of implant osseointegration in type IV bone in the posterior maxilla.     

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.     

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.     

BMP与透明质酸钠复合物对放疗后种植体骨愈合影响的实验研究

目的　 (1)观察放疗对狗下颌种植体周围骨形成蛋白 (BMP)分布与活性的影响 ;(2 )观察局部应用BMP与透明质酸钠复合物对放疗后种植体骨愈合作用的影响。方法　 4只成年雄性杂种狗 ,拔除双侧下颌第 3、4前磨牙和第 1磨牙 ,形成无牙区。拔牙后 3个月 ,用电子直线加速器照射一侧下颌无牙区 ,单一剂量 15Gy。另一侧不接受照射 ,作为对照。放疗后 3个月 ,狗双侧下颌无牙区植入纯钛种植体各 4枚 ,其中每侧各 2枚种植体在局部使用BMP与透明质酸钠的复合物。种植术后 1 5个月和 3个月分别处死 2只动物取材。结果　 (1)放疗侧种植体周围骨的BMP免疫染色范围和强度均明显弱于非放疗侧 ;(2 )局部应用BMP与透明质酸钠的复合物后 ,放疗侧种植体 -骨接触率和骨小梁体积百分比有明显增加。结论　 (1)放疗后种植体周围BMP明显减少 ,活性显著下降 ;(2 )局部应用BMP与透明质酸钠复合物可以加快放疗后狗下颌骨的再生和重建 ,提高放疗后狗下颌纯钛种植体的种植体 -骨接触率和骨小梁体积百分比。     

The effect of combination of recombinant human bone morphogenetic protein-2 and basic fibroblast growth factor or insulin-like growth factor-I on dental implant osseointegration by confocal laser scanning microscopy

BACKGROUND: The healing period of bone-implant osseointegration usually varies from 3 to 6 months or even longer. Failure may occur during this time. This study aimed to investigate whether osseointegration of dental implants can be enhanced by the combination of growth factors. METHODS: Sixty-four implants were coated with polylactic acid and divided into four groups. Group I was applied with 1.0 mg recombinant human bone morphogenetic protein-2 (rhBMP-2) and 200 microg recombinant human basic fibroblast growth factor (rhbFGF), group II with 1.0 mg rhBMP-2 and 250 mug recombinant human insulin-like growth factor-I (rhIGF-I), group III with 1.0 mg rhBMP-2, and group IV without growth factors as control. In total, 16 rabbits were used, and two osteotomies were drilled on each side of the femur, in which four different groups were randomly placed. Four weeks after implanting, 20 mg calcein green/kg body weight was administered intravenously, and 8 weeks after implanting, 20 mg alizarin/kg body weight was administered intravenously. Twelve weeks after implanting, the animals were sacrificed. The block of bone with implants was embedded in methylmethacrylate and sectioned, and the percentage of new bone surrounding the implant was analyzed by confocal laser scanning microscopy. RESULTS: There was a statistical difference in bone formation between rhBMP-2-applied groups and the non-applied group at 4 or 8 weeks, and no significant difference between groups I and II (although bone formation in group II was greater than that in group I at 4 weeks). The bone formation in group II was greater than that in group III at 4 or 8 weeks. The formed bone in group I was also greater than the one in group III at 8 weeks, but there was no difference at 4 weeks. CONCLUSIONS: rhBMP-2 could increase new bone formation, and it acted synergistically with rhbFGF and rhIGF-I to improve bone-implant osseointegration. The combination of rhBMP-2 and rhbFGF (group 1) showed faster growth of new bone than other groups at 8 months.     

Alveolar ridge augmentation with rhBMP-2 and bone-to-implant contact in induced bone.

The objective of this study was to examine alveolar ridge augmentation following implantation of recombinant human bone morphogenetic protein (rhBMP-2) with an allogeneic freeze-dried demineralized bone matrix (DBM) mixed with autologous blood. A second objective was to evaluate bone-to-implant contact in induced bone. Bilateral surgically created supraalveolar ridge defects in five young adult beagle dogs were implanted with the rhBMP-2-DBM-blood device. Transmucosal dental implants were placed at weeks 8 and 16 postsurgery The animals were euthanized 24 weeks following ridge augmentation. Healing was uneventful in all animals. Radiographic observations indicated substantial bone formation, including regions of radiolucency, at week 8. At week 16, the radiolucencies were generally resolved, and the trabecular structure of the induced bone resembled that of the adjacent residual bone. There were no remarkable differences in radiographic observations between weeks 16 and 24 after ridge augmentation. Histologic analysis revealed dense woven and lamellar induced bone. Any residual DBM appeared remineralized, at least in part. A large portion of the dental implants (approximately 70%) were housed in induced bone with evidence of limited crestal resorption. There was no significant difference in bone density between induced and residual bone, and the levels of bone-to-implant contact were similar (approximately 55%). The rhBMP-2 construct used in this study has a potential to augment alveolar ridge defects. Also, no difference in levels of osseointegration may be expected in induced and residual bone following a two-stage procedure of rhBMP-2-induced ridge augmentation and dental implant placement.     

Effect on bone healing of bone morphogenetic protein placed in combination with endosseous implants: a pilot study in beagle dogs

Although dental implants have become an effective treatment modality for the replacement of missing teeth, their predictability relies on successful osseointegration during the healing period. The purpose of this pilot study was to evaluate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on early bone formation within the perforations of dental implants in beagle dogs. Histologic sections were evaluated for the extent of new bone formation within a 1-mm diameter of through-and-through perforations. Data indicated that significantly more bone formation occurred with rhBMP-2-treated sites within the implant perforation (P < 0.01) compared to sites treated with the vehicle alone. This pilot study indicates that rhBMP-2 increases the rate and extent of bone formation in combination with dental implants.     

Micro-CT evaluation of in vivo osteogenesis at implants processed by wire-type electric discharge machining

Titanium surfaces processed by wire-type electric discharge machining (EDM) are microfabricated surfaces with an irregular morphology, and they exhibited excellent in vitro bone biocompatibility. In this study, the efficiency of in vivo osteogenesis on EDM surfaces was investigated by surgically placing screw-shaped EDM-processed and machined-surface implants into the femurs of four Japanese white rabbits. The volume and process of new bone formation were evaluated by an X-ray micro-CT scanner, coupled with histopathological observations at 1, 2, and 4 weeks post-implantation. Before surgical implantation, the surface topography and contact angle of each implant surface were examined. Bone formation increased over time on both implant surfaces, with both implant types yielding statistically equivalent bone volume at 4 weeks post-implementation. However, at 1 week post-implantation, amount of new bone at EDM-processed implant was markedly greater than that at machined-surface implant. Moreover, new bone appeared to initiate directly from the EDM surfaces, while new bone appeared to generate from pre-existing host bone to the machined surfaces. Thus, EDM seemed to be a promising method for surface modification of titanium implants to support enhanced osteogenesis.     

Short-term effects of rhBMP-2-enhanced bone augmentation beyond the skeletal envelope within a titanium cap in rabbit calvarium

BACKGROUND: Recombinant human bone morphogenetic protein (rhBMP)-2 in a bioabsorbable collagen sponge (ACS) carrier supports significant bone formation. However, histomorphometric data on the augmentation of bone formation beyond the skeletal envelope are insufficient. Our objective was to evaluate the short-term effects of rhBMP-2 on bone augmentation beyond the skeletal envelope within a titanium cap in rabbit calvarium. METHODS: Eighteen adult male Japanese white rabbits were used. ACS soak-loaded with rhBMP-2 (100, 500, or 1,000 microg/ml) was placed at the calvarium; controls were packed with ACS alone. After 1 month, the animals were euthanized, and histologic sections were prepared. Newly generated tissue and mineralized bone areas were measured histomorphometrically and expressed as percentage ratios of the total submembranous space area. RESULTS: At all concentrations, a statistically significant difference in the relative height and amount of newly generated tissue was observed between the experimental and control sites. There was a statistically significant difference in the relative amount of mineralized bone between the experimental and control sites in the 1,000-microg/ml group, but no statistically significant differences were observed in the 100-microg/ml and 500-microg/ml groups. CONCLUSION: rhBMP-2/ACS has a short-term effect on bone augmentation beyond the skeletal envelope within a titanium cap in rabbit calvarium.     

The effect of rhBMP-2 around endosseous implants with and without membranes in the canine model

BACKGROUND: Bone morphogenetic protein (BMP) is a potent differentiating agent for cells of the osteoblastic lineage. It has been used in the oral cavity under a variety of indications and with different carriers. However, the optimal carrier for each indication is not known. This study examined a synthetic bioabsorbable carrier for BMP used in osseous defects around dental implants in the canine mandible. METHODS: Twelve canines had their mandibular four premolars and first molar teeth extracted bilaterally. After 5 months, four implants were placed with standardized circumferential defects around the coronal 4 mm of each implant. One-half of the defects received a polylactide/glycolide (PLGA) polymer carrier with or without recombinant human BMP-2 (rhBMP-2), and the other half received a collagen carrier with or without rhBMP-2. Additionally, one-half of the implants were covered with a non-resorbable (expanded polytetrafluoroethylene [ePTFE]) membrane to exclude soft tissues. Animals were sacrificed either 4 or 12 weeks later. Histomorphometric analysis included the percentage of new bone contact with the implant, the area of new bone, and the percentage of defect fill. This article describes results with the PLGA carrier. RESULTS: All implants demonstrated clinical and radiographic success with the amount of new bone formed dependent on the time and presence/absence of rhBMP-2 and presence/absence of a membrane. The percentage of bone-to-implant contact was greater with rhBMP-2, and after 12 weeks of healing, there was approximately one-third of the implant contacting bone in the defect site. After 4 weeks, the presence of a membrane appeared to slow new bone area formation. The percentage of fill in membrane-treated sites with rhBMP-2 rose from 24% fill to 42% after 4 and 12 weeks, respectively. Without rhBMP-2, the percentage of fill was 14% rising to 36% fill, respectively. CONCLUSIONS: After 4 weeks, the rhBMP-2-treated sites had a significantly higher percentage of contact, more new bone area, and higher percentage of defect fill than the sites without rhBMP-2. After 12 weeks, there was no significant difference in sites with or without rhBMP-2 regarding percentage of contact, new bone area, or percentage of defect fill. In regard to these three outcomes, comparing the results with this carrier to the results reported earlier with a collagen carrier in this study, only the area of new bone was significantly different with the collagen carrier resulting in greater bone than the PLGA carrier. Thus, the PLGA carrier for rhBMP-2 significantly stimulated bone formation around dental implants in this model after 1 month but not after 3 months of healing. The use of this growth factor and carrier combination appears to stimulate early bone healing events around the implants but not quite to the same degree as a collagen carrier.     

Effects of anodized implants coated with Escherichia coli-derived rhBMP-2 in beagle dogs

This study evaluated the effects of Escherichia coli-derived rhBMP-2 (ErhBMP-2) coated onto anodized implants to stimulate bone formation, osseointegration and vertical bone growth in a vertical bone defect model. Six young adult beagle dogs were used. After a 2-month bone healing period, anodized titanium implants (8 mm in length) were placed 5.5 mm into the mandibular alveolar ridge. Eighteen implants coated with ErhBMP-2 (BMP group) and another 18 uncoated implants (control group) were installed using a randomized split-mouth design. The implant stability quotient (ISQ) values were measured. Specimens were fabricated for histometric analysis to evaluate osseointegration and bone formation. The ISQ values at 8 weeks after implant placement were significantly higher in the BMP group than in the control group (p < 0.05). Histological observations showed that the changes in bucco-lingual alveolar bone levels were higher in the BMP group than in the control group (p < 0.05). The ErhBMP-2 coated anodized implants can stimulate bone formation and increase implant stability significantly on completely healed alveolar ridges in dogs. Further studies evaluating the effects of ErhBMP-2 on osseointegration in the bone–implant interface are warranted.     

Chronological changes in the ultrastructure of titanium-bone interfaces: analysis by light microscopy, transmission electron microscopy, and micro-computed tomography

Purposes: The objectives of this study were to chronologically examine the titanium-bone interfaces and to clarify the process of osseointegration using light microscopy, transmission electron microscopy (TEM), and micro-computed tomography (CT).
Materials and Methods: Experimental implants (Ti-coating plastic implants) were placed into tibiae of 8-week-old rats. Animals were sacrificed at 1 to 28 days after implant placement and prepared tissue specimens for a light microscope, a TEM, and micro-CT.
Results: New bone formation began 5 days after implant placement, and osseointegration was obtained by 14 days after implant placement. Osseointegration was well developed by 28 days after implant placement.
Discussion: TEM and quantitative computer tomography (QCT) results indicated that bone formation in osseointegration of titanium implants did not occur from the surfaces of the implant or preexisting bone, but it was likely that bone formation progressed at a site a small distance away from the surface. The bone formation took place in a scattered manner. Small bone fragments adhered to each other and transformed into reticular-shaped bone, and finally these bones became lamellar bone.
Conclusion: Comparative analysis of the titanium-bone interfaces using light microscopy, TEM, and QCT by micro-CT revealed the precise process of osseointegration.     

rhBMP-2在种植体周围骨缺损修复中应用的组织学观察

目的:研究rhBMP-2及不同载体在种植体周围骨缺损修复中的应用。方法:在beagle犬下颌骨植入种植体,颊侧形成裂开性骨缺损,置入复合了不同浓度rhBMP-2的珊瑚羟基磷灰石人造骨(CHA)或可吸收胶原海绵(ACS)。种植体植入后2、4、8、12周,获取含种植体骨标本,进行组织学观察。结果:2周时,rhBMP-2组可见极少量的新生骨组织。4周时,rhBMP-2/ACS组新骨组织由牙槽骨顶端向缺损区中心方向生长;rhBMP-2/CHA组人造骨颗粒内部和周围出现呈岛状生长的新生骨组织。8周时,rhBMP-2/ACS组的新骨形成大片状结构;rhBMP-2/CHA组人造骨颗粒周围较多骨岛形成。12周时,rhBMP-2组的缺损区内骨量和骨高度进一步增加,与种植体形成骨性结合。浓度为0.05 mg/ml和0.2 mg/ml,载体为CHA或ACS促进骨再生作用差异无统计学意义。结论:以CHA或ACS为载体rhBMP-2能促进种植体周围骨缺损区内的骨组织再生并与种植体表面较好地结合。