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.     

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.     

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.     

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.     

Experimental study of secondary bone graft of alveolar clefts using bone morphogenetic protein (BMP)

The purpose of this study was to evaluate the utility of recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone substitute on artificial alveolar clefts of adult Macaca fuscata monkeys. First, we created simulated alveolar clefts to represent human bilateral alveolar clefts, and then we implanted a mixture of rhBMP-2 and autogeneous particulate marrow cancellous bone (PMCB) into these models, as experimental groups. The mixture ratio was varied as follows (mixture ratio = rhBMP-2: PMCB). Group 1: rhBMP-2 alone. Group 2: Mixture of rhBMP-2 and PMCB (1:1). Group 3: Mixture of rhBMP-2 and PMCB (3:1). Group 4: Mixture of rhBMP-2 and PMCB (4:1). Positive control group: PMCB alone. Negative control group: PLGA (poly[L-lactide-co-glycolide] copolymer/gelatin sponge complex (PGS) alone. All animals were sacrificed 12 weeks after implantation and evaluated radiographically and histologically. The results were as follows. Bone bridge formation was not observed in Group 1, using rhBMP-2 alone, but it was observed in Groups 2, 3, and 4 using mixture of rhBMP-2 and PMCB. The vertical height of bone bridge formation in Group 4 was equal to that in the positive control group, roughly. The histological finding showed that the bone density of Group 4 was higher than in the positive control group, and the structure of cancellous bone turned into mature type. Bone formation and remodeling was active in Group 4. These results indicated that rhBMP-2 may be an effective substitute for autogenous PMCB in bone grafting into alveolar clefts.     

Ridge augmentation following implantation of recombinant human bone morphogenetic protein-2 in the dog

BACKGROUND: Recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS) carrier induces bone for reconstruction of skeletal defects. The rhBMP-2/ACS implant is prepared by administering a rhBMP-2 solution to dry ACS. Once prepared, rhBMP-2/ACS forms a moldable, cohesive, and adhesive implant. However, rhBMP-2/ACS does not have sufficient structural strength to withstand soft tissue compression at specific anatomic sites. To more fully understand the mechanisms that affect bone induction by rhBMP-2/ACS in the presence of soft tissue compression, it would be useful to have a preclinical model that appropriately simulates such circumstances in patients. This pilot study evaluated one such potential model. METHODS: Bilateral, Class III alveolar defects were surgically produced in 4 adult mongrel dogs following extraction of the mandibular fourth premolars and reduction of the alveolar ridge. After an 8-week healing interval, mucoperiosteal flaps were elevated and rhBMP-2/ACS or rhBMP-2/ACS combined with hydroxyapatite (HA) was implanted into contralateral defects. The animals were euthanized at 12 weeks post-augmentation and block biopsies processed for histologic evaluation. RESULTS: Limited augmentation followed implantation of rhBMP-2/ACS (0.7 +/- 0.6 mm). In contrast, sites receiving rhBMP-2/ACS/HA exhibited clinically relevant ridge augmentation (5.5 +/- 1.6 mm). Defects implanted with rhBMP-2/ACS exhibited dense trabeculation within the corpus of the reduced alveolar process. The cortices appeared intact without evidence of expansion into the defect area. Three defects receiving rhBMP-2/ACS/HA exhibited sparse bone trabeculae amidst HA particles, fibrovascular tissue, and marrow. Commonly, the HA particles were encapsulated by fibrous tissue. Some particles were observed in contact with bone. CONCLUSIONS: The results suggests that rhBMP-2/ACS has limited effect alone in this augmentation model of Class III alveolar ridge defects. Inclusion of HA into the rhBMP-2 construct results in clinically relevant augmentation, however, the quality of bone is compromised.     

Effect of recombinant human bone morphogenetic protein-2 on bone formation in alveolar ridge defects in dogs

This study was designed to evaluate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with poly D, L lactic-co-glycolic acid (PLGA)/gelatin sponge complex (PGS) on the formation of bone in critically sized marginal defects of the mandible in dogs. Three months after extraction of the pre-molar teeth, rectangular bone defects (10 x 8 x 7 mm) were made in both sides of the mandible. A PGS block soaked in rhBMP-2 (400 microgram/ml) was implanted into one defect (BMP (+) group). As control, an untreated PGS block was implanted into the contralateral defect (BMP (-) group). 2, 4, 8, and 12 weeks after implantation, the defects were examined. In the BMP (+) group, newly formed bone was found in all defects from 4 weeks onward and was marked at 12 weeks. In contrast, the BMP (-) group showed no appreciable new bone formation, even at 12 weeks. Moreover, density of newly formed bone in the BMP (+) group was similar to that of the surrounding cortical bone at 12 weeks. These findings suggest that rhBMP-2/PGS is an effective bone substitute for reconstructive surgery of the dog mandible.     

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.     

原核表达重组人骨形态发生蛋白-7对牙槽骨修复再生的实验研究

目的研究原核表达重组人骨形态发生蛋白- 7（rhBMP- 7）对牙槽骨修复再生的影响。方法采用新西兰白兔建立动物模型,以明胶海绵作为载体,将大肠杆菌原核表达的rhBMP- 7与之复合后植入即刻拔除牙齿的牙槽窝内进行干预治疗,术后2、4、8及12周处死动物,取标本进行大体观察、扫描电镜分析、碱性磷酸酶（ALP）活性测定。结果大体观察结果显示,实验组和对照组牙槽嵴高度的吸收差异有显著性;扫描电镜观测显示,实验组的骨创愈合比对照组大约提前4～6周;ALP活性测定显示实验组均明显高于对照组,其差异有统计学意义（P<0.05）。结论原核表达rhBMP- 7具有促进新骨修复再生、防止牙槽骨吸收的作用。     

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.     

Beagle犬下颌重度牙槽嵴萎缩动物模型的建立

目的 建立一种与临床相符的下颌重度牙槽嵴萎缩的动物模型.方法 以Beagle犬为实验动物,拔除其双侧下颌第四前磨牙和第一磨牙,在距下颌第三前磨牙及下颌第二磨牙釉牙骨质界8 mm处的牙槽嵴上水平磨一凹线,咬骨钳去除该线上方的牙槽骨,用骨凿将去骨区域修平,形成25 mm×8 mm大小的箱状缺损洞形,置入无菌硅胶假体,严密缝合后,待其自然愈合.术后8周行锥形束CT检查.结果 骨改建8周后术区牙槽嵴顶呈圆弧形,嵴顶最低点至下牙槽神经管的距离平均2.5 mm.结论 本研究成功构建了Beagle犬下颌重度牙槽嵴萎缩动物模型,为进行垂直骨增量相关实验奠定了实验基础.     

Lateral ridge augmentation using particulated or block bone substitutes biocoated with rhGDF-5 and rhBMP-2: an immunohistochemical study in dogs

Objectives: The aim of the present study was to immunohistochemically evaluate lateral ridge augmentation using a particulated (BOG) or block (BOB) natural bone mineral biocoated with rhGDF-5 and rhBMP-2 in dogs.
Materials and methods: Three standardized box-shaped defects were surgically created at the buccal aspect of the alveolar ridge in each quadrant of eight beagle dogs. After 2 months of healing, the chronic-type defects were randomly allocated in a split-mouth design to either (i) BOG or (ii) BOB biocoated with (a) rhGDF-5 or (b) rhBMP-2, respectively. Uncoated grafts served as controls. After 3 and 8 weeks, dissected blocks were prepared for immunohistochemical [osteocalcin (OC)] and histomorphometrical analysis [e.g. area (mm²) of new bone fill (BF), newly formed mineralized (MT) and non-mineralized tissue (NMT)].
Results: rhBMP-2 biocoated BOG revealed significantly highest BF and MT values at 3 (upper and lower jaws – UJ/LJ – compared with BOG) and 8 weeks (UJ – compared with rhGDF-5). Biocoating of BOB using both rhGDF-5 and rhBMP-2 resulted in significantly increased MT values at 8 weeks (UJ/LJ – compared with BOB). In all groups, NMT adjacent to BOG and BOB scaffolds revealed pronounced signs of an OC antigen reactivity.
Conclusions: Within the limits of the present study, it was concluded that both rhGDF-5 and rhBMP-2 have shown efficacy; however, their bone regenerative effect was markedly influenced by the carrier.     

Hyaluronan supports recombinant human bone morphogenetic protein-2 induced bone reconstruction of advanced alveolar ridge defects in dogs. A pilot study

BACKGROUND: Prosthetic-driven implant dentistry requires predictable procedures for alveolar ridge augmentation. The objective of this pilot study was to evaluate bone regeneration in mandibular, full-thickness, alveolar ridge, saddle-type defects following surgical implantation of recombinant human bone morphogenetic protein-2 (rhBMP-2) in a novel hyaluronan (HY) sponge carrier. This sponge was fabricated from auto-crosslinked HY. METHODS: Alveolar ridge defects (approximately 15 x 10 x 10 mm), 2 per jaw quadrant, were surgically prepared in each of 3 young adult American fox hounds. Four defects were immediately implanted with rhBMP-2/HY. Three defects were implanted with rhBMP-2 in an absorbable collagen sponge (ACS) carrier (positive control). The rhBMP-2 solution (1.5 ml at 0.2 mg/ml) was soak-loaded onto the HY and ACS sponges. Three defects were implanted with HY sponges soak-loaded with buffer without rhBMP-2 (negative control), while 2 defects served as surgical controls. The animals were euthanized at 12 weeks postsurgery for histometric analysis. RESULTS: Clinically, alveolar ridge defects receiving rhBMP-2/ACS exhibited a slight supracrestal expansion, while defects receiving rhBMP-2/HY were filled to contour. In contrast, the HY and surgical controls exhibited ridge collapse. rhBMP-2/HY-treated defects exhibited a dense bone quality without radiolucent regions observed in defects treated with rhBMP-2/ACS. The histometric analysis showed 100% bone fill for the rhBMP-2/ACS defects and 94%, 58%, and 65% bone fill for the rhBMP-2/HY, HY, and surgical control defects, respectively. CONCLUSIONS: The conclusions are based on data from 2 of 3 animals in the study. In one animal, no response to rhBMP-2 was observed with either carrier, and the animal may have been a non-responder of unknown nature. With this limitation, the observations herein suggest that: 1) HY supports significant bone induction by rhBMP-2; 2) the rhBMP-2-induced bone assumes qualities of the immediate resident bone; 3) HY alone exhibits no apparent osteoconductive potential; and 4) HY appears to resorb within a 12-week healing interval in the absence or presence of rhBMP-2. Thus, HY appears to be a suitable candidate carrier for rhBMP-2.     

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.     

Peri-implant bone regeneration using recombinant human bone morphogenetic protein-2 in a canine model: a dose-response study

The objective of this study was to evaluate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) dose on alveolar ridge augmentation and dental implant osseointegration. Bilateral, 5 mm supraalveolar, peri-implant defects were surgically created in 6 beagle dogs. rhBMP-2 (0.05, 0.1 or 0.2 mg/ml) in an absorbable collagen sponge (ACS) carrier was molded around the fixtures and wounds were closed. Treatment variations were alternated between animals (incomplete block design). Animals were sacrificed at week 8 postsurgery. Nine of twelve jaw quadrants healed uneventfully. Two jaw quadrants exhibited wound failure by week 4 and one by week 8 postsurgery. Radiographic bone regeneration was observed in defects without wound failure from week 4 postsurgery. Radiolucent voids of variable size and shape were observed and regressed over time. In weeks 6 through 8, there was an apparent increase in bone density and trabecular structure, while bone height and volume decreased. Histometric analysis revealed limited differences in bone regeneration between experimental conditions. Bone regeneration area averaged (+/- SD) 1.0 +/- 0.5, 3.5 +/- 1.4 and 2.3 +/- 0.4 mm2 for the 0.05, 0.1 and 0.2 mg/ml dose, respectively. There were no significant differences in osseointegration. Osseointegration in newly formed bone averaged 19 +/- 4%, 18 +/- 10% and 21 +/- 6% for the 0.05, 0.1 and 0.2 mg/ml rhBMP-2 sites, respectively. Collectively, the data suggest that there are no dramatic differences in bone induction and osseointegration within the selected dose and observation interval.     

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.     

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.     

Enhanced bone augmentation by controlled release of recombinant human bone morphogenetic protein-2 from bioabsorbable membranes

BACKGROUND: The present study was undertaken to determine the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded biodegradable membranes on bone augmentation in a rabbit calvarial model. METHODS: Five microg of rhBMP-2 was loaded into a stiff hemispherical dome membrane made of poly(L-lactide) and tricalcium phosphate (PLLA/TCP). The release kinetics of rhBMP-2 from the membrane were determined in vitro using a human BMP-2 immunoassay. Twelve rhBMP-2-loaded dome membranes (test group) and 12 control dome membranes (control group) were placed on the partial-thickness calvarial defects of 24 rabbits. The animals were sacrificed at 4 and 8 weeks, and undecalcified ground sections were prepared. Newly formed bone area and height were measured histomorphometrically and calculated by percentage ratio to the total submembranous space area and height below the dome. RESULTS: In vitro release results demonstrated that rhBMP-2 was released consistently over a 4-week period following a high initial burst release on the first day. At both 4 and 8 weeks, histomorphometric analysis revealed that the test group showed significantly higher newly formed bone heights and areas than the control group (P < 0.01). In the control group, new bone height was 36.3% of the dome height and the new bone area reached 8.2% of the submembranous space area at 8 weeks, while the test group reached 87.3% and 35.4%, respectively. CONCLUSION: These results suggest that the use of rhBMP-2-loaded PLLA/TCP membranes can result in additional bone augmentation, which is due to the osteoinductive properties of rhBMP-2 released from the membrane during healing.     

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.     

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.