Formation and resolution of ankylosis under application of recombinant human bone morphogenetic protein-2 (rhBMP-2) to class III furcation defects in cats

OBJECTIVES: Periodontal regeneration under application of bone morphogenetic protein (BMP) is compromised by ankylosis. Ankylosis disappearance following application of BMP has been observed in the case of a small defect, which might be beneficial change for periodontal regeneration. However, the histological observation of ankylosis disappearance has not been demonstrated in a large defect. The purpose of this present study was to confirm resolution of ankylosis during periodontal regeneration by recombinant human BMP-2 (rhBMP-2) applied to class III furcation defects. MATERIAL AND METHODS: Class III furcation defects were created in the premolars of six adult cats. The rhBMP-2 material, prepared by applying rhBMP-2 to a combination of polylactic acid-polygricolic copolymer and gelatin sponge (PGS; 0.33 microg rhBMP-2/mm(3) PGS) or control material containing only PGS, was implanted into each defect. The cats were killed at 3, 6 or 12 weeks after surgery and serial sections were prepared for histological and histometrical observation. RESULTS: Ankylosis was observed in some of the rhBMP-2/PGS group at 3 and 6 weeks, but not at 12 weeks. At 6 weeks, osteoclast-like cells were visible in the rhBMP-2/PGS group with ankylosis. Residual PGS was evident between the bone and root surface in the rhBMP-2/PGS group without ankylosis at 3 weeks. CONCLUSIONS: Resolution of ankylosis by osteoclast-like cells possibly occurred under application of rhBMP-2. Residual PGS might play an important role in preventing ankylosis formation.     

Bone regeneration by recombinant human bone morphogenetic protein-2 in rat mandibular defects. An experimental model of defect filling.

BACKGROUND: Bone defects and irregularities are major problems for dental implant and periodontal therapies. METHODS: We investigated whether the application of recombinant human bone morphogenetic protein-2 (rhBMP-2) induces bone formation in through-and-through bone defects in the rat mandible. A round through-and-through bone defect (5 mm in diameter) was created in the angle of the mandible on both sides of the jaw using a steel round bur in each of 8 Long-Evans rats. In the experimental group, polylactic acid-polyglycolic acid copolymer/gelatin sponge (PGS) containing rhBMP-2 (6 microg/60 microl) was inserted in the bone defect. In the control group, the same carrier without rhBMP-2 was applied in the bone defect on the opposite side. Four weeks after application, the rats were sacrificed. Step serial sections stained with hematoxylin and eosin at intervals of 200 microm were prepared in a bucco-lingual direction. The size of the bone defects and new bone formation were evaluated histometrically. RESULTS: In all cases in the experimental group, a large quantity of newly formed bone was observed. The bone defects were completely filled with new bone in 4 of 8 rats in the experimental group. In the control group, small amounts of new bone formation were observed along the border of the original mandibular bone. Histometrical analysis revealed that the amount of new bone was significantly larger in the rhBMP-2 treated sites than in the control sites (P <0.0001; paired t-test). CONCLUSIONS: These results indicate that the rhBMP-2/PGS system induced effective bone regeneration on mandibular defects in rats. This procedure may be suitable as an experimental model for bone regeneration using various growth factors and effective for alveolar ridge augmentation followed by dental implant surgery.     

The use of polylactic acid/polyglycolic acid copolymer and gelatin sponge complex containing human recombinant bone morphogenetic protein-2 following condylectomy in rabbits.

PURPOSE: To examine the results of a polylactic acid/polyglycolic acid copolymer and gelatin sponge complex (PGS) with or without recombinant human bone morphogenetic protein-2 (rhBMP-2) used to treat condylar defects in rabbits. MATERIAL AND METHODS: Adult male Japanese white rabbits (n=60; 3kg; 12-16 weeks old) were divided into three groups of 20 each. All rabbits underwent condylectomy. In the two implanted groups, PGS with or without 5 microg of rhBMP-2 was implanted to the condylar defect without fixation. No material was implanted into the control group. Animals were sacrificed at 2, 4, 8, 12 and 24 weeks postoperatively, and the temporomandibular joints (TMJs) were examined histologically. RESULTS: Four weeks after implantation, growth of bone and cartilage-like tissue was observed in all rabbits that received PGS implants (with and without rhBMP-2). A cartilage-like layer was derived from the bone marrow at the operated surface. There was no growth of bone tissue in the control rabbits, but they also had a cartilage-like layer directly derived from the operated surface. CONCLUSION: This study demonstrated that PGS with or without rhBMP-2 could induce regeneration of new bone and cartilage-like tissue in the TMJ.     

Bone regeneration using recombinant human bone morphogenetic protein-2 (rhBMP-2) in alveolar defects of primate mandibles

The efficacy of bone morphogenetic protein (BMP) for bone reconstruction has been widely studied in numerous animal experiments, but insufficient information exists about its ability to regenerate bone in primates. The purpose of this study was to evaluate the effects of recombinant human BMP-2 (rhBMP-2) on bone formation in alveolar bone defects in the mandibles of young primates. Marginal bone defects were created in the mandibles of nine 5-year-old rhesus monkeys and rhBMP-2 permeated in a polylactic-co-glycolic acid-coated gelatin sponge (PGS) was implanted into the bone defects. The resected bone treated with rhBMP-2 regenerated completely at 12 weeks postoperatively, and remodelling and consolidation of new bone were seen histologically. This study provides evidence of considerable bone regeneration in alveolar defects after surgical implantation of rhBMP-2 in non-human primates. This technique may be an effective alternative to autogenous bone grafts for reconstructive surgery in clinical practice.     

Functional reconstruction of the non-human primate mandible using recombinant human bone morphogenetic protein-2

The purpose of this study was to evaluate the long-term functional properties of regenerated bone induced by recombinant human bone morphogenetic protein-2 (rhBMP-2) in segmental bone defects of primate mandibles. The 30-mm defects were created in the mandibles of six young monkeys and the mandibles were fixed with titanium plates. Then 9 mg of rhBMP-2 permeating a poly-D, L-lactic-co-glycolic acid-coated gelatin sponge (PGS) was implanted into the bone defect. Dental implants were placed into the regenerated mandible 20 weeks after surgery, then suprastructures were placed and masticatory force loading was begun 8 weeks after the insertion of the dental implants. Bone formation and the quality of new bone were evaluated radiologically and histologically at 15 and 30 weeks after surgery, and 4 and 24 weeks after masticatory force loading. The resected mandibles were completely regenerated with the rhBMP-2-induced bone. Excellent remodelling and consolidation of new bone were observed after loading. This study demonstrated that the new bone induced by rhBMP-2 in large segmental defects was maintained and functional for at least 1 year. Bone regeneration induced by rhBMP-2 holds promise as a future therapy and may be an effective alternative to autogenous bone grafts for implant dentistry and reconstructive surgery.     

聚乳酸与重组人骨形成蛋白—2复合植入块修复兔下颌骨缺损…

采用冷冻干燥法，将聚乳酸（ＰＬＡ）制成多孔成形块状，并将ＰＬＡ与重组人骨形成蛋白－２（ｒｈＢＭＰ－２）有效的复合，植入兔下颌骨缺损动物模型，在术后２，４周通过Ｘ线片、组织学观察缺损部位的骨生成情况。结果表明：ＰＬＡ－ｒｈＢＭＰ－２植入组术后２周就有部分新骨形成，术后４周骨生成明显；而单独植入ＰＬＡ组术后４周仅有少量新骨生成。钙含量测定显示ＰＬＡ－ｒｈＢＭＰ－２组高于ＰＬＡ组。结果提示：ＰＬＡ为ＢＭ     

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.     

Enhancement of bone formation by bone morphogenetic protein-2 during alveolar distraction: an experimental study in sheep

BACKGROUND: The purpose of this study was to perform alveolar ridge augmentation by distraction osteogenesis (DO) and to enhance bone regeneration through the use of recombinant human bone morphogenetic protein-2 (rhBMP-2), followed by implant placement. METHODS: Alveolar segmental osteotomy was performed in the mandible of 10 sheep followed by placement of 1.5 mm alveolar distraction devices. The study group was injected on the fifth day of distraction with a single dose of 10 microg rhBMP-2. Only distraction was performed in the control group. RESULTS: A mean alveolar augmentation of 12 mm was achieved. After 12 weeks of consolidation, the distraction devices were removed and biopsies were taken for histological and immunohistochemical characterization and morphometry of the newly formed bone. Titanium threaded cylindrical implants were then placed in the newly augmented bone. Radiological evaluation showed lifting of the transport segment and integration of the implants within both the transport segment and the regenerated bone. The histological study demonstrated that the association of DO and BMP resulted in increased trabecular bone size and volume (32.2%+/-0.95% versus 18.6%+/-0.71%; P <1 x 10(-17) after 24 days of lengthening and 63.8%+/-1.89% versus 42.5%+/-1.33%; P<1 x 10(-15) after 12 weeks of consolidation) and increased numbers of proliferating cell nuclear antigen stained cells (0.7+/-0.04 versus 0.47+/-0.04; P<1 x 10(-10)) compared with the DO only group. CONCLUSIONS: Alveolar distraction augments atrophic alveolar ridge and creates new bone that permits implant placement. rhBMP-2 enhances bone quality and may shorten the consolidation period of distraction allowing for earlier implant placement.     

Effect of recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge with space-providing biomaterials on the augmentation of chronic alveolar ridge defects

BACKGROUND: Recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS) carrier has been shown to support significant bone formation in the craniofacial skeleton. When used as an onlay, however, rhBMP-2/ACS may become compressed with limited resulting bone formation. The objective of this study was to evaluate the effect of two space-providing biomaterials, bioactive glass (BG) and demineralized/mineralized bone matrix (DMB), on rhBMP-2/ACS induced alveolar ridge augmentation. METHODS: Bilateral alveolar ridge defects were produced in the mandible in six mongrel dogs. rhBMP-2/ACS with biomaterials was surgically implanted into contralateral defects in four animals. Treatments were alternated between jaw quadrants in consecutive animals. Two animals received rhBMP-2/ACS or sham-surgery in contralateral defects. The animals were injected with fluorescent bone labels to monitor bone formation. Clinical evaluations were made at ridge augmentation and 12 weeks post-implantation when the animals were euthanized and block biopsies collected for histopathologic evaluation. RESULTS: Sham-surgery produced limited horizontal alveolar augmentation (0.1 +/- 0.6 mm). Implantation of rhBMP-2/ACS resulted in alveolar augmentation amounting to 2.2 +/- 1.8 mm. Alveolar augmentation in sites receiving rhBMP-2/ACS with DMB or BG was 2-fold greater compared to rhBMP-2/ACS alone averaging 4.4 +/- 1.3 and 4.6 +/- 1.5 mm, respectively. The DMB biomaterial appeared substituted by newly formed bone. The BG particles were observed imbedded in bone or encapsulated in dense connective tissue without associated bone metabolic activity. Fluorescent light microscopy suggested that the new bone was formed within 4 weeks. CONCLUSION: The bioglass and demineralized/mineralized bone matrix biomaterials utilized in this study in combination with rhBMP-2/ACS supported clinical and histological ridge augmentation.     

Effect of rhBMP-2 with PLGA/gelatin sponge type (PGS) carrier on alveolar ridge augmentation in dogs

Summary  Recombinant human bone morphogenetic protein-2 has been shown to promote bone formation because of its osteoinductive property. The purpose of this study was to evaluate the efficacy of rhBMP-2 delivered on a poly ( d , l -lactic-co-glycolic acid) copolymer/gelatin sponge (PGS) in vertical alveolar ridge augmentation on height-reduced edentulous mandible to verify the retention of rhBMP-2 withstanding the pressure of soft tissues. Coronal defects of the alveolar bone were created in six adult beagle dogs. After a healing period of 9 weeks, PGSs with or without rhBMP-2 (0 or 0·4 mg mL⁻¹) were implanted on the defects(6 mm in height, 30 mm in length, 8 mm in width). Sixteen weeks after implantation, the bone mineral content (BMC) and the total bone area were measured by peripheral quantitative computed tomography. The BMC and the total bone area of the defect sites with rhBMP-2 group were significantly greater (133 ± 33 mg mm⁻¹, 277 ± 54 mm², respectively) than those of the control group (80 ± 19 mg mm⁻¹, 155 ± 49 mm², respectively) ( P  <   0·01, P  <   0·0001, respectively; paired t -test). From the histological analyses, the height of newly formed bone in the experimental group was greater than that of the control group (4·3 ± 0·9 mm, 0·22 ± 0·28 mm, P  <   0·0001, n  = 6, paired t -test). These results indicate that PGS has characteristics of effective bone graft substitutes for implantation of rhBMP-2 on vertical alveolar ridge augmentation in huge defect of mandibles in dogs.     

Enhanced vertical alveolar bone augmentation by recombinant human bone morphogenetic protein-2 with a carrier in rats

This study aimed to evaluate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on vertical bone regeneration of edentulous ridge. Bilateral upper first and second molars of 8-week-old Wistar rats were extracted and the ridges were allowed to heal for 3 weeks. Compressed poly(lactic-co-glycolic acid) copolymer/gelatin sponge (PGS) was used as a carrier of rhBMP-2. PGS alone (control group) or PGS with 5 mug rhBMP-2 (test group) was implanted at the top part of alveolar ridge. The sham group received no implantation. The rats were killed at 1, 2, 4, 8 and 12 weeks after implantation and examined histologically and histomorphometrically. In the test group, significant bone augmentation was evident on the alveolar ridge throughout the experimental period. Histomorphometric analysis revealed greater tissue volume and height of alveolar bone in the test group compared with the control and sham groups (P < 0.05) from 4 weeks onward and the augmented tissues (5 mm3 in tissue volume and 1.5 mm in bone height) were maintained until 12 weeks. Osteoblast surface increased at 2 and 4 weeks and osteoid thickness reached a peak (25 microm) at 2 weeks. Dynamic variables, which represented calcification, were higher in the test group than the control and sham groups at 4 and 8 weeks (P < 0.05). These results suggest that use of rhBMP-2/PGS may achieve vertical bone augmentation, and stabilizes denture prosthesis or makes up for inadequate bone mass for implant prosthesis.     

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.     

基因修饰的组织工程化骨修复骨质疏松症骨缺损的实验研究

目的 探讨人类骨形成蛋白2（hBMP-2）基因修饰的组织工程化骨修复骨质疏松症者骨缺损的可行性及方法。方法24只6个月龄雌性SD大鼠建立去势模型，按体重编号，随机分组。3个月后实验组骨髓问质干细胞（BMSC）转染hBMP-2质粒，对照组未作干预，在体外构建自体细胞组织工程化骨，植入下颌骨缺损区。结果术后4周时实验组有新生骨质形成，8周时成熟骨基质形成；对照组新生骨质数量明显少于实验组，且材料边缘及中央处有脂肪样结构形成。结论hBMP-2基因修饰的组织工程化骨可用于骨质疏松症者骨缺损的治疗。     

Effect of aging on bone formation induced by recombinant human bone morphogenetic protein-2 combined with fibrous collagen membranes at subperiosteal sites

This study was designed to examine the effect of aging on bone formation induced by recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with a fibrous collagen membrane (FCM). Implantation was done subperiosteally in bilateral palatal grooves in 34 male Wistar rats divided into three age groups: a 10-week-old group (10w group), a 30-week-old group (30w group) and a 70-week-old group (70w group). RhBMP-2-combined FCMs were implanted on the left palatal grooves as BMP-implanted sites (BMP site), while rhBMP-2 was not implanted on the right palatal grooves as control sites. The rats were sacrificed 6 weeks after implantation, and histometric evaluations were performed. New bone formation was observed in every site of each age group and the new bone was almost completely continuous with the original bone. The new bone volume (NBV) of the BMP site was significantly higher than that of the control site in each age group. The NBV of both the control and BMP sites were highest in the 10w group and lowest in the 70w group. The disparity of NBV between the control and BMP sites, which indicated the response to implanted BMP excluding the effect of skeletal growth and surgical stimulation, did not significantly differ among the age groups. These results indicate that rhBMP-2-combined FCM has the ability to induce new bone formation continuous with original bone even in senescent rats. Furthermore, it appeared that, in the case of palatal subperiosteal implantation, the responsiveness to implanted BMP was independent of age, although the total volume of newly formed bone declined with aging.     

Reconstruction of the primate mandible with a combination graft of recombinant human bone morphogenetic protein-2 and bone marrow.

PURPOSE: This study evaluated whether recombinant human bone morphogenetic protein-2 (rhBMP-2) can be used to regenerate a resected part of the mandible in a primate model. MATERIALS AND METHODS: Segmental bone defects were created surgically in the mandible of Japanese monkeys. rhBMP-2 was suspended in a solution of polyglycolic co-lactic acid (PGLA) and lyophilized to make a BMP/PGLA complex. The rhBMP-2/PGLA complex and autogenous bone marrow in ratios of 3:0, 2.5:0.5, or 2:1 (vol:vol) were each implanted into the bone defects in 3 monkeys. Bone marrow or P(GLA alone were each implanted in 1 monkey as a control. The animals were killed 16 weeks after surgery, followed by radiologic and histologic evaluation. RESULTS: The implantation of bone marrow alone succeeded in reconstruction of the mandible, but the implantation of the rhBMP-2/PGLA complex showed only a small amount of bone formation. The combination graft of rhBMP-2/PGLA and bone marrow resulted in a greater degree of bone formation; especially the 2:1 combination showed the same result as only bone marrow implantation. CONCLUSION: The combination graft of rhBMP-2 and bone marrow, which requires only a small amount of bone marrow, was a reliable method for reconstruction of mandibular segmental defects in this animal model.     

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。     

重组人骨形成蛋白—2—珊瑚复合人工骨修复骨缺损的生物力…

将珊瑚与具有骨诱导特性的重组形成蛋白－２（ｒｈＢＭＰ－２）复合，制成ｒｈＢＭＰ－２＝ｃｏｒａｌ复合人工骨，将其植入兔颅骨标准大小缺损，并与单纯珊瑚植入作对照。通过Ｘ线片、组织学和生物力学方法来评价此复合人工骨的骨修复能力。结果显示：ｒｈＢＭＰ－２－ｃｏｒａｌ复合人工骨具有较强的骨修复作用，植入骨缺损后，材料被逐渐降解吸收，新骨不断形成，机械强度不断增大；１２周后，植入物完全被成熟的骨组织取代，缺损     

Restoration of occlusal function using osseointegrated implants in the canine mandible reconstructed by rhBMP-2

Abstract: Bone morphogenetic proteins have been found to be one of the most promising osteoinductive substances and they are expected to be utilized clinically for the reconstruction of defective mandibles. However, newly formed bone induced by recombinant human bone morphogenetic protein-2 (rhBMP-2) has not yet been proven able to withstand the masticatory force applied by oral implants. In this study, we examined the qualitative changes in an rhBMP-2-induced mandible from the functional force of osseointegrated oral implants. Segmental (30 mm) bone defects were created in the mandibles of beagles. A poly D,L-lactic coglycolic acid-coated gelatin sponge impregnated with rhBMP-2 was grafted to the resected canine mandible. The new bone was formed 8 weeks after surgery and the Brånemark system fixtures were implanted into the reconstructed mandible. After another 8 weeks, the prosthesis was placed over the oral implants. The prosthesis was maintained in occlusion with the opposing natural dentition for 0, 4, 12, 24, or 48 weeks before the animal was euthanized. The quality of regenerated bone was then evaluated histologically and the osseointegration ratio between oral implants and the bonemeasured. During the first 4 weeks, the ratio remarkably increased from 48.9% to 64.5%. After 48 weeks, the ratio approached about 74.5%. The bone loaded for 48 weeks had undergone extensive remodeling and consolidation; its quality was better and maturer than that of bone that was not loaded. These results indicated that the newly formed bone induced by rhBMP-2 was able to withstand the masticatory force applied by oral implants and had become as functionally mature as a natural bone.     

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.     

Favorable healing following space creation in rhBMP-2-induced periodontal regeneration of horizontal circumferential defects in dogs with experimental periodontitis

BACKGROUND: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is believed to be capable of inducing periodontal regeneration. However, the risk of aberrant healing events, such as root resorption and ankylosis, has been reported. We hypothesized that implantation of BMP-containing carriers directly on the root planed surface may be the cause of unfavorable healing. The purpose of this study was to evaluate the influence of a 1 mm spacer membrane, which separated the rhBMP-2 in polymer-coated gelatin sponge (PGS) and the root surface, on periodontal regeneration of experimentally induced horizontal defects in dogs. METHODS: Horizontal circumferential periodontal defects were surgically created, and experimental periodontitis was induced in 72 maxillary and mandibular premolars of four male beagle dogs. The recipient sites of each quadrant received: 1) rhBMP-2/PGS (B group) (rhBMP-2 at 1.0 mg/ml, total implant volume/ site approximately 7.2 microl) (n = 24); 2) rhBMP-2/PGS with a spacer membrane (PB group) (n = 24); and 3) physiological saline (PS)/PGS as a control (P group) (n = 24). One quadrant was left untreated. Dogs were sacrificed at 12 weeks post-surgery, and healing was evaluated histologically. RESULTS: Both groups treated with rhBMP-2/PGS demonstrated enhanced new bone formation and connective tissue attachment with cementum regeneration when compared to the control group. Sites treated with rhBMP-2/PGS showed a greater degree of bone formation than sites treated with rhBMP-2/PGS and spacer membrane, although the latter sites showed no ankylosis. CONCLUSIONS: Implantation of rhBMP-2/PGS enhances bone formation and connective tissue attachment in horizontal circumferential defects. In addition, the use of a spacer membrane reduces the degree of bone formation, but minimizes ankylosis.