Recombinant human bone morphogenetic protein-2 stimulation of bone formation around endosseous dental implants

BACKGROUND: Successful endosseous implant placement requires that the implant be stable in alveolar bone. In certain cases, the implant can be stabilized in native bone but some part of the implant is not covered by bone tissue. This often occurs during placement of implants into extraction sites or in areas where bone resorption has occurred and the ridge width is not sufficient to completely surround the implant. In those cases, the clinician usually employs a procedure to encourage bone formation. These procedures typically include a bone graft and/or membrane therapy. Recent advances have led to the isolation, cloning, and production of recombinant human proteins that stimulate bone formation. One of these bone morphogenetic proteins (rhBMP-2) has been extensively studied in animal models and is currently being tested in human clinical trials. METHODS: In this study, rhBMP-2 was tested using a collagen sponge carrier to stimulate bone formation in defects in the canine mandible around endosseous dental implants. Six animals had a total of 48 implants placed. rhBMP-2 with the collagen carrier was implanted around 24 of these, the remainder having only the collagen carrier placed. Half the sites were covered with a nonresorbable expanded polytetrafluoroethylene membrane. Histologic analysis was performed after 4 and 12 weeks. The area of new bone formed, percentage of bone-to-implant contact in the defect area, and percentage fill of the defect was calculated. RESULTS: The addition of rhBMP-2 resulted in significantly greater amounts of new bone area and percentage of bone-to-implant contact and with more percentage fill after 4 and 12 weeks of healing. The area of new bone formed was reduced after 4 weeks when a membrane was present but after 12 weeks, there was no significant difference between membrane and non-membrane treated sites. In some specimens, new bone was found coronal to the membranes, with rhBMP-2-treated sites having greater amounts than non-rhBMP-2-treated sites. CONCLUSIONS: These data demonstrate that a bone differentiation factor significantly stimulates bone formation in peri-implant bone defects in the canine mandible. In addition, bone-to-implant contact was significantly enhanced along the rough implant surface. Membrane-treated sites had less new bone formation after 4 weeks of healing but were similar to non-membrane sites after 12 weeks. These results demonstrate that rhBMP-2 can be used to stimulate bone growth both around and onto the surface of endosseous dental implants placed in sites with extended peri-implant osseous defects.     

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.     

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.     

Bone regeneration around implants in the canine mandible with cultured fibroblasts in polyglactin mesh

BACKGROUND: Human fibroblast-derived dermal substitute (HFDDS) is a tissue-engineered material that consists of polyglactin mesh seeded with cultured fibroblasts. Cultured fibroblasts are not as differentiated as tissue fibroblasts and retain the ability to differentiate into other cells types. HFDDS also is capable of stimulating angiogenesis and wound healing. The purpose of this study was to attempt to evaluate the effects of HFDDS on guided bone regeneration at sites with 1.5-mm peri-implant defects in the canine mandible. METHODS: Fifty sand-blasted acid-etched test implants were placed into the edentulous areas of mandibular ridges of five American foxhounds. Each site had a standardized 1.5-mm circumferential peri-implant defect in the coronal half of the implant, created by a specialized drill at the time of osteotomy. In each canine two implants received no treatment of the defects, four implants were treated with polyglactin mesh (carrier only) wrapped around the circumference of the defect wall, and four implants were treated with HFDDS placed in a similar fashion to the mesh. Implant sites healed submerged for 10 weeks, at which time sacrifice took place and sections were prepared, processed, and analyzed histomorphometrically. RESULTS: The mean distance from the top of the fixture to the first point of bone-implant contact was 2.20 mm, 2.25 mm, and 2.60 mm for the HFDDS, carrier, and control sites, respectively (P = 0.202). Overall mean percentage of bone-to-implant contact (BIC) in the defects was 32.8%, 31.0%, and 22.8% for the HFDDS, carrier, and control groups, respectively. These differences were not statistically significant, but approached statistical significance for the control group compared to HFDDS and carrier (P = 0.057). Overall mean bone fill in the defects calculated histometrically was 36.0%, 35.8%, and 33.9% for the HFDDS, carrier, and control groups, respectively. These differences were not statistically significant. Sites with dehiscence at the time of implant placement had significantly greater distance to first bone-implant contact (P = 0.002), a smaller percentage of BIC (P = 0.006), and significantly less bone fill (P = 0.006) in the defects. It was consistently found that when dehiscence occurred on the buccal side of the implant, the outcomes for all parameters measured were significantly inferior on the lingual side as well. Factorial analysis, which grouped outcomes by dehiscence categories (none, partial, or full dehiscence), revealed that with intact defects without dehiscence, HFDDS had less bone fill compared to the carrier. However, in defects with partial or full dehiscence, HFDDS had more bone fill compared to carrier sites. These differences were statistically significant (P = 0.034). CONCLUSIONS: In intact sites without dehiscence, the presence of cultured fibroblasts in 1.5-mm-wide peri-implant defects did not significantly enhance bone regeneration compared to the carrier, polyglactin mesh. However, sites with partial or full dehiscence treated with HFDDS had significantly greater bone fill compared to the carrier (P = 0.034). When dehiscence occurs during immediate implant placement on narrow ridges without the use of membranes, bone regeneration tends to be inferior on the side of the dehiscence as well as the opposite side of the implant.     

Evaluation of titanium implants placed into simulated extraction sockets: a study in dogs.

The purpose of this study was to evaluate the effect of gap width on bone healing around implants placed into simulated extraction socket defects of varying widths in 10 mongrel dogs. All premolars were removed and the alveolar ridges were reduced to a width of 7 mm. Nine weeks later, a total of 80 implants, 10 mm long by 3.3 mm wide, were placed into osteotomy sites prepared to 3 different diameters in the coronal half, simulating extraction sockets. Three experimental sites, with gap sizes of 0.5 mm, 1.0 mm, and 1.4 mm, were created; the control sites had no gap. The depth of each defect was measured at the time of implant placement. All implants were stable at the time of placement. The dogs were euthanized 12 weeks after implant placement, and blocks containing the implants and adjacent bone were submitted for histologic evaluation. Clinically, all control and test sites healed, with complete bone fill in the defect. Percentages of bone-to-implant contact were measured histologically. As the gap widened, the amount of bone-to-implant contact decreased, and the point of the highest bone-to-implant contact shifted apically. These changes were statistically significant (P < .001). No statistically significant differences in bone-to-implant contact were found between the sites when the apical 4 mm of implants were compared. Within the limits of this study, the simulated extraction socket defects healed clinically, with complete bone fill, regardless of the initial gap size. However, the width of the gap at the time of implant placement had a significant impact on the histologic percentage and the height of bone-to-implant contact.     

Comparative analysis of collagen membranes for the treatment of implant dehiscence defects

Guided bone regeneration (GBR) evolved from the concept of guided tissue regeneration (GTR) and has been used for reconstructing sites with bone deficiencies associated with dental implants. For GBR, the use of absorbable collagen membranes has been increasing, but, at present, scientific information on the use of collagen membranes for GBR is limited. This study was aimed to clinically and histomorphometrically compare two collagen membranes, Bio-Gide(R) and BioMend ExtendTM, for the treatment of implant dehiscence defects in eight mongrel dogs. Implant dehiscence defects were surgically created in edentulous ridges, followed by the placement of three endosseous implants bilaterally in the mandible. Each implant dehiscence defect was randomly assigned to one of three treatment groups: (1) control (no membrane), (2) porcine dermis collagen barrier (Bio-Gide) or (3) bovine tendon collagen barrier (BioMend Extend). Dogs were sacrificed at 4 and 16 weeks (four dogs each) after treatment. Histomorphometric analysis included percentage linear bone fill (LF), new bone-to-implant contact (BIC) and area of new bone fill (BF). The results of the study revealed no significant differences among groups for any parameter at 4 weeks. However, at 16 weeks, more LF, BIC, and BF were noted in the membrane-treated groups than controls. BioMend Extend-treated defects demonstrated significantly greater BIC than control (P < 0.05) at this time point. BIC at 16 weeks was significantly greater than 4-week BIC (P < 0.05). Membrane exposure occurred in 9 out of 15 sites examined, resulting in significantly less LF and BIC than the sites without membrane exposure (P < 0.05). The results of this study indicate that: (1) GBR treatment with collagen membranes may significantly enhance bone regeneration, manifested at late stage (16 weeks) of healing; and (2) space maintenance and membrane coverage were the two most important factors affecting GBR using bioabsorbable collagen membranes.     

即刻种植后采用GBR术和植入PRF对骨结合影响的实验研究

目的：比较研究即刻种植后用GBR术和植入PRF对种植体周骨缺损区的成骨能力。方法：以成年Bea-gle犬为实验动物,拔除犬双侧下颌P2、 P3、 P4牙,即刻植入种植体,所植入的种植体距近中根拔牙窝的近中壁有3～4mm的骨缺损间隙,采用半口自身对照,一侧行即刻种植＋GBR （A组）,一侧即刻种植＋PRF （B组）,术后三个月处死动物,取下带有种植体的下颌骨标本,进行组织学观察。对两组种植体周围的骨结合率和新骨生成率运用统计软件SPSS13.0进行统计学分析。结果： A组、 B组骨缺损处3个月时均被新骨充填,两组种植体周围的骨结合率和新骨生成率差异无统计学意义。结论：限于本研究中,即刻种植术中采用GBR和植入PRF对骨缺损区的引导骨再生效果相同。     

Bone apposition around two different sandblasted, large-grit and acid-etched implant surfaces at sites with coronal circumferential defects: an experimental study in dogs

Objective: The study was designed to evaluate bone apposition around SLA (sandblasted, large-grit and acid-etched) implants compared with modified SLA (modSLA) ones at sites with different sizes of circumferential gaps.
Material and methods: All mandibular premolars and first molars of six beagle dogs were extracted. After a healing period of 3 months, three 10-mm-long implants were inserted in each side of the mandible. One implant was inserted with a 0.5-mm and one with a 1-mm gap between the implants and bone around the coronal 5 mm of the implants. The third implant was inserted without a gap as a control. The dogs were sacrificed respectively at weeks 2, 4 and 8 after implant placement for histological and histomorphometric analyses.
Results: The histomorphometric results showed similar pattern of bone apposition for the two surfaces. At 2 and 4 weeks of healing, the percentage of newly formed bone-to-implant contact (BIC%), new bone fill (NBF%) and the distance between the most coronal position of BIC and the defect bottom (B–D) were significantly higher for modSLA ( P <0.05). At 8 weeks of healing, this difference was not significant ( P >0.05). With regard to the defect size, the histological analyses showed no significant differences between the two defect sizes at all time points ( P >0.05).
Conclusion: Significantly more bone apposition was found for the modSLA surface than for the SLA surface at early stage of healing, indicating that modSLA surface may enhance bone apposition in coronal circumferential defects at non-submerged implants. Gap size within 1 mm may not need any kind of regenerative procedures.     

Effects of the platelet-derived growth factor/insulin-like growth factor-I combination on bone regeneration around titanium dental implants. Results of a pilot study in beagle dogs.

The purpose of this study was to evaluate the early wound healing events of bone around press-fit titanium implants inserted with and without the concurrent application of a combination of platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF-I). Nine months prior to implant placement all mandibular premolar teeth were extracted in 8 beagle dogs. Subsequently, 40 specially manufactured titanium implants with 2 transverse holes in the apical section were press fit into precise recipient sites in the dogs' mandibles. The dogs were sacrificed at 7 and 21 days following implant placement yielding 12 PDGF-B/IGF-I treated and 8 control (placebo gel or non-treated) implants for each observation period. Coded undecalcified sections were analyzed for: 1) percentage of implant surface in contact with new bone; 2) percentage of peri-implant space filled with new bone; and 3) percentage of implant hole filled with new bone. An analysis of variance was used to determine significant differences among the treatment groups. At 7 days, the percentage of bone fill in the peri-implant spaces and the percentage of implant surface in contact with new bone were both significantly increased in PDGF-B/IGF-I treated sites (P less than 0.01 for both groups). There was less than 1.5% fill of the implant holes in both treated and control sites (no significant differences). At 21 days the percentage of bone fill in the peri-implant spaces was significantly increased in the PDGF-B/IGF-I treated sites (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

TM种植体-骨结合界面的显微CT观察

目的 研究TM种植体-骨结合界面及其上 1/3倒楔形间隙的成骨情况.方法 用医用钝钛钛棒加工成两组种植体,实验组为锥度5.44°、表面进行喷砂酸蚀处理的TM种植体,锥度从种植体上1/3处开始变化;对照组为仿straumann的表面喷砂酸蚀(sandblast large grit and acid-etching,SLA)圆柱状螺纹种植体.建立Beagle犬下颌骨种植模型,3只犬每只植入实验组TM种植体和对照组仿straumann -SLA圆柱状螺纹种植体各4枚,3只实验犬分别于4周、8周和12周处死,截取下颌骨行显微CT三维重建,观察种植体-骨结合界面及上1/3间隙的成骨情况.结果 8周时实验组TM种植体上1/3倒楔形间隙开始有骨修复,12周时对照组仿straumann-SLA种植体颈部骨质有吸收迹象,实验组TM种植体颈部骨质仍得到良好保存.结论 TM种植体能形成良好骨结合界面,体部上1/3的锥度设计可保存颈部皮质骨.     

Evaluation of recombinant human bone morphogenetic protein-2 on the repair of alveolar ridge defects in baboons

BACKGROUND: The objective of this study was to evaluate alveolar ridge augmentation following surgical implantation of recombinant human bone morphogenetic protein-2 (rhBMP-2) using two novel space-providing carrier technologies in the baboon (Papio anubis) model. METHODS: Standardized alveolar ridge defects ( approximately 15 x 8 x 5 mm) were surgically produced in maxillary and mandibular edentulous areas in four baboons. The defect sites were implanted with rhBMP-2 (0.4 mg/mL) in a tricalcium phosphate/hydroxyapatite/ absorbable collagen sponge composite (TCP/HA/ACS) or calcium phosphate cement (alpha-BSM). Control treatments were TCP/HA/ACS and ?-BSM without rhBMP-2 and sham surgery. Stainless steel pins were placed at the mid-apical and coronal level of the defect sites to provide landmarks for clinical measurements pre- and post-implantation. Impressions were obtained pre- and postimplantation to determine changes in alveolar ridge volume. Radiographic registrations were obtained pre- and post-implantation. Block sections of the defect sites were harvested at week 16 postimplantation and processed for histometric analysis including new bone area and bone density. Statistical comparisons between treatments were made using a mixed effect generalized linear model using least squares estimation. RESULTS: The carrier systems without rhBMP-2 provided a modest ridge augmentation. The addition of rhBMP-2 resulted in an almost 2-fold increase in alveolar ridge width, including a greater percentage of trabecular bone and a higher bone density compared to controls (P < or =0.05) without significant differences between the two rhBMP-2 protocols. CONCLUSIONS: TCP/HA/ACS and alphaBSM appear to be suitable carrier technologies for rhBMP-2. Alveolar augmentation procedures using either technology combined with rhBMP-2, rather than stand-alone therapies, may provide clinically relevant augmentation of alveolar ridge defects for placement of endosseous dental implants.     

Periodontal repair in dogs: effect of recombinant human bone morphogenetic protein-12 (rhBMP-12) on regeneration of alveolar bone and periodontal attachment

OBJECTIVES: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been shown to stimulate alveolar bone and cementum formation in periodontal defects but not a functionally oriented periodontal ligament (PDL). Subcutaneous and intramuscular implants of BMP-12 have been shown to induce tendon formation and ligament-like tissue. The objective of this study was to evaluate rhBMP-12 for periodontal regeneration, in particular PDL formation. METHODS: Six young adult Hound Labrador mongrel dogs were used. Routine supraalveolar periodontal defects were created around the mandibular premolar teeth. Three animals received rhBMP-12(0.04 mg/ml) in an absorbable collagen sponge (ACS) carrier vs. rhBMP-12(0.2 mg/mL)/ACS in contralateral defects. Three animals received rhBMP-12(1.0 mg/ml)/ACS vs. rhBMP-2(0.2 mg/ml)/ACS (total implant volume/defect approximately 1 ml). The animals were euthanized 8 weeks postsurgery and block biopsies were processed for histometric analysis. RESULTS: Bone regeneration appeared increased in sites receiving rhBMP-2/ACS compared to sites receiving rhBMP-12/ACS. Cementum regeneration was similar comparing sites implanted with rhBMP-2/ACS to sites implanted with rhBMP-12/ACS. In contrast, sites receiving rhBMP-12/ACS exhibited a functionally oriented PDL bridging the gap between newly formed bone and cementum whereas this was a rare observation in sites receiving rhBMP-2/ACS. Ankylosis appeared increased in sites receiving rhBMP-2/ACS compared to those receiving rhBMP-12/ACS. CONCLUSIONS: The outcomes of this study suggest that rhBMP-12 may have significant effects on regeneration of the PDL. Additional preclinical evaluation is needed to confirm these initial observations prior to clinical application.     

Effect of autologous bone marrow-derived cells associated with guided bone regeneration or not in the treatment of peri-implant defects

This study investigated the effect of bone marrow-derived cells associated with guided bone regeneration in the treatment of dehiscence bone defects around dental implants. Iliac-derived bone marrow cells were harvested from dogs and phenotypically characterized with regard to their osteogenic properties. After teeth extraction, three implant sites were drilled, dehiscences created and implants placed. Dehiscences were randomly assigned to: bone marrow-derived cells, bone marrow-derived cells+guided bone regeneration, and control (no treatment). After 3 months, implants with adjacent tissues were processed histologically, bone-to-implant contact, bone fill within the threads, new bone area in a zone lateral to the implant, new bone height, and new bone weight at the bottom of the defect were determined. Phenotypic characterization demonstrated that bone marrow-derived cells presented osteogenic potential. Statistically higher bone fill within the threads was observed in both bone marrow-derived cells+guided bone regeneration bone marrow-derived cell groups compared with the control group (P<0.05), with no difference between the groups treated with cells (P>0.05). For the other parameters (new bone area, bone-to-implant contact, new bone height and new bone weight), only the bone marrow-derived cells+guided bone regeneration group presented higher values compared with the non-treated control (P<0.05). Bone marrow-derived cells provided promising results for peri-implantar bone regeneration, although the combined approach seems to be relevant, especially to bone formation out of the implant threads.     

Bone reconstruction following implantation of rhBMP-2 and guided bone regeneration in canine alveolar ridge defects

BACKGROUND: Alveolar ridge aberrations commonly require bone augmentation procedures for optimal placement of endosseous dental implants. The objective of this study was to evaluate local bone formation following implantation of recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS) carrier with or without provisions for guided bone regeneration (GBR) as potential treatment modalities for alveolar augmentation. METHODS: Surgically induced, large, mandibular alveolar ridge saddle-type defects (2 defects/jaw quadrant) in seven young adult Hound dogs were assigned to receive rhBMP-2/ACS, rhBMP-2/ACS combined with GBR (rhBMP-2/GBR), GBR, and surgery controls. The animals were euthanized at 12 weeks post-surgery when block sections of the defect sites were collected for histologic analysis. RESULTS: Clinical complications included swelling for sites receiving rhBMP-2 and wound failure with exposure of the barrier device for sites receiving GBR (4/6) or rhBMP-2/GBR (3/7). The radiographic evaluation showed substantial bone fill for sites receiving rhBMP-2/ACS, rhBMP-2/GBR, and GBR. In particular, sites receiving rhBMP-2/GBR presented with seroma-like radiolucencies. The surgery control exhibited moderate bone fill. To evaluate the biologic potential of the specific protocols, sites exhibiting wound failure were excluded from the histometric analysis. Sites receiving rhBMP-2/ACS or rhBMP-2/GBR exhibited bone fill averaging 101%. Bone fill averaged 92% and 60%, respectively, for sites receiving GBR and surgery controls. Bone density ranged from 50% to 57% for sites receiving rhBMP-2/ACS, GBR, or surgery controls. Bone density for sites receiving rhBMP-2/GBR averaged 34% largely due to seroma formation encompassing 13% to 97% of the sites. CONCLUSION: rhBMP-2/ACS appears to be an effective alternative to GBR in the reconstruction of advanced alveolar ridge defects. Combining rhBMP-2/ACS with GBR appears to be of limited value due to the potential for wound failure or persistent seromas.     

Bone augmentation by recombinant human BMP-2 and collagen on adult rat parietal bone.

A composite of recombinant human bone morphogenetic protein-2 (rhBMP-2) and collagen was implanted beneath the cranial periosteum of 10-month-old rats to observe bone development and absorbent change of carrier collagen. The rhBMP-2/collagen onlay implant resulted in active bone formation and the augmented bone was connected directly with the original bone, whereas the collagen alone resulted in neither bone nor cartilage. The ossification process in the rhBMP-2/collagen occurred directly through bone formation, similar to intramembranous ossification. The carrier collagen fibers were found in the woven bone and were completely absorbed at 8 weeks in the presence of rhBMP-2, while the collagen alone implant remained encapsulated by a thin, fibrous connective tissue. Our results indicate that rhBMP-2/collagen is an effective material as a biological onlay implant, showing osteoinductive properties and being completely replaced by new bone. Carrier collagen not only plays a role in rhBMP-2 delivery, but also provides a cell anchorage for cell differentiation and remains as an artificial matrix in woven bone.     

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.     

rhBMP-2/PLA复合涂层种植体骨内诱导成骨的实验研究

目的：观察基因重组人骨形成蛋白-（recombinanthuman bone morphogenetic protein-2，rhBMP-2）和聚乳酸（polylactic acid，PLA）复合形成的活性涂层种植体骨内诱导成骨活性。方法：将rhBMP-2与聚乳酸复合构建活性涂层种植体，植入兔股骨内，分别于4，8，12，16周处死动物，进行组织学及扫描电镜及组织化学观察，检测其成骨活性。结果：构建的活性涂层种植体具有骨诱导能力，PLA为rhBMP-2的良好控释载体。结论：rhBMP-2/PLA涂层具有良好的生物相容性和骨诱导活性，是一种理想的种植体形式。     

Healing of dehiscence defects at delayed-immediate implant sites primarily closed by a rotated palatal flap following extraction

In 21 patients, 28 maxillary teeth were extracted because of periapical or periodontal infection, root fracture, or untreatable caries. A rotated palatal flap procedure was used to achieve primary soft tissue closure over extraction sites. At 5 to 7 weeks postextraction, 28 implants were placed. Buccal dehiscence-type defects were treated with guided bone regeneration procedures using bovine bone mineral and resorbable collagen membranes. Mean defect area at the time of implant placement (23.7 mm2, SD 11.49) was significantly reduced at uncovering (0.7 mm2, SD 0.99). The mean percentage of defect reduction (clinical bone fill) was 97% (SD 4.26). Implants placed in compromised sites shortly postextraction according to the presented 2-stage protocol gave good short-term clinical results.     

Guided bone regeneration at dehiscence-type defects using biphasic hydroxyapatite + beta tricalcium phosphate (Bone Ceramic) or a collagen-coated natural bone mineral (BioOss Collagen): an immunohistochemical study in dogs

The aim of this study was to immunohistochemically investigate bone regeneration following application of either hydroxyapatite+beta tricalcium phosphate (BCG) or a collagen-coated natural bone mineral (BOC) in combination with a collagen membrane at dehiscence-type defects in dogs. Standardized buccal dehiscence defects were surgically created following implant bed preparation in six beagle dogs. Defects were randomly filled with either BOC (BioOss Collagen) or BCG (Bone Ceramic) according to a split-mouth design, and covered with a native porcine derived collagen membrane (BioGide). After 1, 4 and 9 weeks of submerged healing, dissected blocks were processed for immunohistochemical (osteocalcin) and histomorphometrical analysis (residual defect length, new bone-implant contact, area of new bone fill, percentage of osseointegrated bone-graft particles). Both groups revealed a significant decrease in mean residual defect length, and increases in mean new bone-implant contact, bone fill and percentage of osseointegrated bone-graft particles after 4 and 9 weeks of healing. Remaining BCG and BOC granules were completely integrated into a secondarily formed network of spongiosa, but there was no osteoclastic activity at the surface of either type of bone-graft particle. Both BCG and BOC may provide an osteoconductive scaffold to support guided bone regeneration procedures at dehiscence-type defects.     

活性胶原基纳米骨修复即刻种植体周围骨缺损的研究

目的:观察胶原基纳米骨(nHAC)及活性胶原基纳米骨(AnHAC)修复即刻钛种植体周围骨缺损的效果,为临床应用奠定理论依据。方法:犬下颌骨拔牙创区制造即刻种植体周围骨缺损,分别采用植入nHAC、AnHAC、自体牙槽松质骨及不植入任何材料4种不同方法修复种植体周骨缺损,术后6周、12周,采用X线摄片、骨密度测量及组织学检查,观察新骨形成情况和新骨与种植体的关系。结果:两组实验动物中,除空白对照组外,骨缺损区均愈合良好,未见种植体周围炎发生。1)nHAC组:术后6周已有新生骨小梁形成,术后12周修复骨缺损,种植体边缘可见较多新骨形成;2)AnHAC组:成骨过程较早,术后6周即有较多新生骨组织出现,术后12周新骨组织与宿主骨完全融合,并与种植体表面形成广泛的骨性结合。结论:nHAC具有良好的骨引导作用,可良好地修复种植体周骨缺损,复合rhBMP-2后效果更佳。临床上可根据具体情况选用修复即刻种植体周围骨缺损的方法。