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Human Bone Morphogenetic (human + bone_morphogenetic)
Kinds of Human Bone Morphogenetic Terms modified by Human Bone Morphogenetic Selected AbstractsRepair of segmental defects in rabbit humeri with titanium fiber mesh cylinders containing recombinant human bone morphogenetic protein-2 (rhBMP-2) and a synthetic polymerJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 2 2002Narumichi Murakami Abstract To develop a new technology that enhances the regeneration potential of bone and the repair of large intercalated defects in long bone, recombinant human bone morphogenetic protein-2 (BMP-2; 20 ,g or 40 ,g) was mixed in a polymer gel (poly-lactic acid-polyethyleneglycol block copolymer; PLA-PEG; 200 mg) and incorporated into titanium fiber-mesh cylinders. Three 5-mm cylinders were placed end-to-end to fill a 15-mm defect created in the humeri of adult rabbits and were stabilized by an intramedullary rod. In controls, the titanium fiber-mesh cylinders were combined with PLA-PEG in the absence of BMP. Six weeks after implantation, new bone had formed on the surface of the implant and had bridged the defect. All of the defects (5/5) treated by cylinders containing 120 ,g (40 ,g × 3) of BMP were repaired completely. New bone formation was also found inside the pores of the cylinders. The defect was not repaired in the control animals. These results demonstrate that these new composite implants fabricated by combining rhBMP, synthetic degradable polymers and compatible biomaterials enhance the regeneration potential of bone. Thus, it is possible that large skeletal defects can be repaired using this prosthesis in lieu of autogenous bone graft. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 169,174, 2002 [source] Alveolar ridge augmentation using implants coated with recombinant human bone morphogenetic protein-7 (rhBMP-7/rhOP-1): histological observationsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 6 2010Cristiano Susin Susin C, Qahash M, Polimeni G, Lu PH, Prasad HS, Rohrer MD, Hall J, Wikesjö UME. Alveolar ridge augmentation using implants coated with recombinant human bone morphogenetic protein-7 (rhBMP-7/rhOP-1): histological observations. J Clin Periodontol 2010; 37: 574,581. doi: 10.1111/j.1600-051X.2010.01554.x. Abstract Background: Pre-clinical studies have shown that recombinant human bone morphogenetic protein-2 (rhBMP-2) coated onto purpose-designed titanium porous-oxide surface implants induces clinically relevant bone formation and osseointegration. The objective of this study was to examine the potential of rhBMP-7, also known as recombinant human osteogenic protein-1 (rhOP-1), coated onto titanium porous-oxide surface implants to support vertical alveolar ridge augmentation and implant osseointegration. Materials and Methods: Bilateral, critical-size, 5 mm, supraalveolar peri-implant defects were created in six young adult Hound Labrador mongrel dogs. The animals received implants coated with rhBMP-7 at 1.5 or 3.0 mg/ml randomized to contra-lateral jaw quadrants. The mucoperiosteal flaps were advanced, adapted, and sutured to submerge the implants for primary intention healing. The animals received fluorescent bone markers at 3, 4, 7, and 8 weeks post-surgery when they were euthanized for histological evaluation. Results: Without striking differences between treatments, the implant sites exhibited a swelling that gradually regressed to become hard to palpation disguising the implant contours. The histological evaluation showed robust bone formation; the newly formed bone assuming characteristics of the contiguous resident bone, bone formation (height and area) averaging 4.1±1.0 versus 3.6±1.7 mm and 3.6±1.9 versus 3.1±1.8 mm2; and bone density 56%versus 50% for implants coated with rhBMP-7 at 1.5 and 3.0 mg/ml, respectively. Both treatments exhibited clinically relevant osseointegration, the corresponding bone,implant contact values averaging 51% and 47%. Notable peri-implant resident bone remodelling was observed for implants coated with rhBMP-7 at 3.0 mg/ml. Conclusions: rhBMP-7 coated onto titanium porous-oxide surface implants induces clinically relevant local bone formation including osseointegration and vertical augmentation of the alveolar ridge, the higher concentration/dose associated with some local side effects. [source] Evaluation of implants coated with rhBMP-2 using two different coating strategies: a critical-size supraalveolar peri-implant defect study in dogsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 6 2010Jaebum Lee Lee J, Decker JF, Polimeni G, Cortella CA, Rohrer MD, Wozney JM, Hall J, Susin C, Wikesjö UME. Evaluation of implants coated with rhBMP-2 using two different coating strategies: a critical-size supraalveolar peri-implant defect study in dogs. J Clin Periodontol 2010; 37: 582,590. doi: 10.1111/j.1600-051X.2010.01557.x. Abstract Background: Implants coated with recombinant human bone morphogenetic protein-2 (rhBMP-2) induce relevant bone formation but also resident bone remodelling. Objectives: To compare the effect of implants fully or partially coated with rhBMP-2 on new bone formation and resident bone remodelling. Materials and Methods: Twelve, male, adult, Hound Labrador mongrel dogs were used. Critical-size, supraalveolar, peri-implant defects received titanium porous oxide surface implants coated in their most coronal aspect with rhBMP-2 (coronal-load/six animals) or by immersion of the entire implant in an rhBMP-2 solution (soak-load/six animals) for a total of 30 ,g rhBMP-2/implant. All implants were air-dried. The animals were euthanized at 8 weeks for histometric evaluation. Results: Clinical healing was uneventful. Supraalveolar bone formation was not significantly affected by the rhBMP-2 application protocol. New bone height and area averaged (± SE) 3.4 ± 0.2 versus 3.5 ± 0.4 mm and 2.6 ± 0.4 versus 2.5 ± 0.7 mm2 for coronal-load and soak-load implants, respectively (p>0.05). The corresponding bone density and bone,implant contact (BIC) recordings averaged 38.0 ± 3.8%versus 34.4 ± 5.6% and 25.0 ± 3.8%versus 31.2 ± 3.3% (p>0.05). In contrast, resident bone remodelling was significantly influenced by the rhBMP-2 application protocol. Bone density outside the implants threads averaged 74.7 ± 3.8% and 50.8 ± 4.1% for coronal-load and soak-load implants, respectively (p<0.05); bone density within the thread area averaged 51.8 ± 1.2% and 37.8 ± 2.9%, and BIC 70.1 ± 6.7% and 43.3 ± 3.9% (p<0.05). Conclusion: Local application of rhBMP-2 appears to be a viable technology to support local bone formation and osseointegration. Coronal-load implants obviate resident bone remodelling without compromising new bone formation. [source] Bone formation at recombinant human bone morphogenetic protein-2-coated titanium implants in the posterior maxilla (Type IV bone) in non-human primatesJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 11 2008Ulf M. E. Wikesjö Abstract Background: Studies using ectopic rodent and orthotopic canine models (Type II bone) have shown that titanium porous oxide (TPO) surface implants adsorbed with recombinant human bone morphogenetic protein-2 (rhBMP-2) induce local bone formation including osseointegration. The objective of this study was to evaluate local bone formation and osseointegration at such implants placed into Type IV bone. Material and Methods: rhBMP-2-coated implants were installed into the edentulated posterior maxilla in eight young adult Cynomolgus monkeys: four animals each received three TPO implants adsorbed with rhBMP-2 (2.0 mg/ml) and four animals each received three TPO implants adsorbed with rhBMP-2 (0.2 mg/ml). Contra-lateral jaw quadrants received three TPO implants without rhBMP-2 (control). Treatments were alternated between left and right jaw quadrants. Mucosal flaps were advanced and sutured to submerge the implants. The animals received fluorescent bone markers at weeks 2, 3, 4, and at week 16 when they were euthanized for histologic analysis. Results: Clinical healing was uneventful. Extensive local bone formation was observed in animals receiving implants adsorbed with rhBMP-2 (2.0 mg/ml). The newly formed bone exhibited a specific pinpoint bone,implant contact pattern regardless of rhBMP-2 concentration resulting in significant osseointegration; rhBMP-2 (2.0 mg/ml): 43% and rhBMP-2 (0.2 mg/ml): 37%. Control implants exhibited a thin layer of bone covering a relatively larger portion of the implant threads. Thus, TPO control implants bone exhibited significantly greater bone,implant contact (,75%; p<0.05). There were no statistically significant differences between rhBMP-2-coated and control implants relative to any other parameter including peri-implant and intra-thread bone density. Conclusion: rhBMP-2-coated TPO implants enhanced/accelerated local bone formation in Type IV bone in a dose-dependent fashion in non-human primates resulting in significant osseointegration. rhBMP-2-induced de novo bone formation did not reach the level of osseointegration observed in native resident bone within the 16-week interval. [source] Alveolar ridge augmentation using implants coated with recombinant human bone morphogenetic protein-2: histologic observationsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 11 2008Ulf M. E. Wikesjö Abstract Background: Studies using ectopic rodent, orthotopic canine, and non-human primate models show that bone morphogenetic proteins (BMPs) coated onto titanium surfaces induce local bone formation. The objective of this study was to examine the ability of recombinant human BMP-2 (rhBMP-2) coated onto a titanium porous oxide implant surface to stimulate local bone formation including osseointegration and vertical augmentation of the alveolar ridge. Material and Methods: Bilateral, critical-size, 5 mm, supra-alveolar, peri-implant defects were created in 12 young adult Hound Labrador mongrel dogs. Six animals received implants coated with rhBMP-2 at 0.75 or 1.5 mg/ml, and six animals received implants coated with rhBMP-2 at 3.0 mg/ml or uncoated control. Treatments were randomized between jaw quadrants. The mucoperiosteal flaps were advanced, adapted and sutured to submerge the implants for primary intention healing. The animals received fluorescent bone markers at weeks 3, 4, 7 and 8 post-surgery when they were euthanized for histologic evaluation. Results: Jaw quadrants receiving implants coated with rhBMP-2 exhibited gradually regressing swelling that became hard to palpate disguising the contours of the implants. The histologic evaluation showed robust bone formation reaching or exceeding the implant platform. The newly formed bone exhibited characteristics of the adjoining resident Type II bone including cortex formation for sites receiving implants coated with rhBMP-2 at 0.75 or 1.5 mg/ml. Sites receiving implants coated with rhBMP-2 at 3.0 mg/ml exhibited more immature trabecular bone formation, seroma formation and peri-implant bone remodelling resulting in undesirable implant displacement. Control implants exhibited minimal, if any, bone formation. Thus, implants coated with rhBMP-2 at 0.75, 1.5 and 3.0 mg/ml exhibited significant bone formation (height and area) compared with the sham-surgery control averaging (±SD) 4.4±0.4, 4.2±0.7 and 4.2±1.2 versus 0.8±0.3 mm; and 5.0±2.2, 5.6±2.2 and 7.4±3.5 versus 0.7±0.3 mm2, respectively (p<0.01). All the treatment groups exhibited clinically relevant osseointegration. Conclusions: rhBMP-2 coated onto titanium porous oxide implant surfaces induced clinically relevant local bone formation including vertical augmentation of the alveolar ridge and osseointegration. Higher concentrations/doses were associated with untoward effects. [source] Alveolar ridge augmentation using implants coated with recombinant human bone morphogenetic protein-7 (rhBMP-7/rhOP-1): radiographic observationsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 10 2008Knut N. Leknes Abstract Aim: The objective of this study was to radiographically evaluate the potential of a purpose-designed titanium porous-oxide implant surface coated with recombinant human bone morphogenetic protein-7 (rhBMP-7), also known as recombinant human osteogenic protein-1 (rhOP-1), to stimulate alveolar ridge augmentation. Material and Methods: Six young-adult Hound Labrador mongrel dogs were used. Three 10 mm titanium oral implants per jaw quadrant were placed 5 mm into the alveolar ridge in the posterior mandible following surgical extraction of the pre-molar teeth and reduction of the alveolar ridge leaving 5 mm of the implants in a supra-alveolar position. The implants had been coated with rhBMP-7 at 1.5 or 3.0 mg/ml and were randomized to contralateral jaw quadrants using a split-mouth design. The mucoperiosteal flaps were advanced, adapted, and sutured to submerge the implants. Radiographic registrations were made immediately post-surgery (baseline), and at weeks 4 and 8 (end of study). Results: rhBMP-7-coated implants exhibited robust radiographic bone formation. At 8 weeks, bone formation averaged 4.4 and 4.2 mm for implants coated with rhBMP-7 at 1.5 and 3.0 mg/ml, respectively. There were no significant differences between the rhBMP-7 concentrations at any observation interval. A majority of the implant sites showed voids within the newly formed bone at week 4 that generally resolved by week 8. The newly formed bone assumed characteristics of the resident bone. Conclusions: The titanium porous-oxide implant surface serves as an effective carrier for rhBMP-7 showing a clinically significant potential to stimulate local bone formation. [source] Bone formation at rhBMP-2-coated titanium implants in the rat ectopic modelJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 5 2007Jan Hall Abstract Background: The objective of this study was to evaluate local bone formation at titanium porous oxide (TPO) implant surfaces adsorbed with recombinant human bone morphogenetic protein-2 (rhBMP-2). Methods: In vitro studies were used to estimate the kinetics of I125 -labeled rhBMP-2 released from TPO surfaces with narrow (N) or open (O) pores. Machined/turned titanium (MT) surfaces served as control. The rat ectopic model was used to assess local bone formation. Briefly, TPO-N, TPO-O, and MT disc implants adsorbed with 5, 10, or 20 ,g rhBMP-2, respectively, were implanted subcutaneously into the ventral thoracic region in 5-week-old male Long Evans rats. The animals were euthanized at day 14 postsurgery when implants with surrounding tissues were removed, radiographed, and gross observations recorded. The specimens were processed for histologic evaluation using conventional cut-and-grind techniques. TPO implants without rhBMP-2 included in a preliminary evaluation revealed no evidence of bone formation, tissue encapsulation, or vascularity, thus such controls were not further used. Results: TPO and MT implant surfaces adsorbed with 5 ,g rhBMP-2 retained 2.3,5.4% rhBMP-2 following immersion and rinse in buffer, and 1.1,2.2% rhBMP-2 following repeated immersions and rinses over 27 days. TPO implants retained the most rhBMP-2 and MT implants retained the least. Explants revealed increased hard tissue formation, tissue encapsulation, and vascularity at TPO compared with MT implants. Radiographic observations were consistent with the explant observations. The histologic analysis showed greater amounts of bone formation, osteoblastic cells, osteoid, marrow, tissue encapsulation, vascularity, and bone voids for implants adsorbed with 10 and 20 ,g rhBMP-2, and for TPO implants at the 5- ,g rhBMP-2 dose. The histometric analysis revealed significantly greater bone formation at TPO-O than at MT implants at the 5- ,g rhBMP-2 dose. All surfaces showed significant bone formation at the 10- and 20- ,g dose. Conclusions: rhBMP-2 adsorbed onto TPO implant surfaces executes an osteoinductive effect including bone contacting the implant surface. This effect is surface- and dose-dependent; the TPO-O surface yielding the most bone at the low discriminating rhBMP-2 dose. [source] Periodontal repair in dogs: space-providing ePTFE devices increase rhBMP-2/ACS-induced bone formationJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 8 2003Ulf M.E. Wikesjö Abstract Background: Recombinant human bone morphogenetic protein-2 (rhBMP-2) technologies have been shown to enhance alveolar bone formation significantly. Biomaterial (carrier) limitations, however, have restricted their biologic potential for indications where compressive forces may limit the volume of bone formed. The objective of this proof-of-principle study was to evaluate the potential of a space-providing, macroporous ePTFE device to define rhBMP-2-induced alveolar bone formation using a discriminating onlay defect model. Methods: Routine, critical size, 5,6 mm, supra-alveolar, periodontal defects were created around the third and fourth mandibular premolar teeth in four young adult Hound Labrador mongrel dogs. All jaw quadrants received rhBMP-2 (0.4 mg) in an absorbable collagen sponge (ACS) carrier. Contralateral jaw quadrants in subsequent animals were randomly assigned to receive additionally the dome-shaped, macroporous ePTFE device over the rhBMP-2/ACS implant or no additional treatment. The gingival flaps were advanced to cover the ePTFE device and teeth, and sutured. Animals were scheduled for euthanasia to provide for histologic observations of healing at 8 weeks postsurgery. Results: Healing was uneventful without device exposures. New bone formation averaged (±SD) 4.7±0.2 mm (98%) and 4.5±0.4 mm (94%) of the defect height, respectively, for jaw quadrants receiving rhBMP-2/ACS with the ePTFE device or rhBMP-2/ACS alone (p>0.05). In contrast, the regenerated bone area was significantly enhanced in jaw quadrants receiving rhBMP-2/ACS with the ePTFE device compared to rhBMP-2/ACS alone (9.3±2.7 versus 5.1±1.1 mm2; p<0.05). Cementum formation was similar for both treatment groups. Ankylosis compromised periodontal regeneration in all sites. Conclusions: The results suggest that the novel space-providing, macroporous ePTFE device appears suitable as a template to define rhBMP-2/ACS-induced alveolar bone formation. Zusammenfassung Hintergrund: Es wurde gezeigt, dass das rekombinante menschliche knochenmorphogenetische Protein 2 (rhBMP-2) die alveoläre Knochenbildung signifikant erhöht. Limitationen des Biomaterials (Träger) haben jedoch die biologischen Potenzen des Materials für die Indikationen, wo komprimierende Kräfte das Volumen des zu bildenden Knochen limitierten, eingeengt. Das Ziel dieser prinzipiellen geprüften Studie war die Evaluation der Platzhalterfunktion einer makroporösen e-PTFE Membran, um die von rhBMP-2 induzierten Knochenbildung unter Nutzung eines differenzierenden Onlaydefektmodells zu definieren. Methoden: Routinemäßig wurden supraalveoläre parodontale Defekte mit der kritischen Größe von 5,6 mm um die dritten und vierten Prämolaren bei 4 jungen adulten Labrodormischhunden geschaffen. Alle Quadranten erhielten rhBMP-2 (0.4 mg) in einem resorbierbaren Kollagenschwamm (ACS). Kontralaterale Quadranten bei den aufeinander folgenden Tieren wurden zufällig ausgewählt, um zusätzlich eine domförmige makroporöse e-PTFE Membran über das rhBMP-2/ACS Implantat oder keine zusätzliche Therapie zu erhalten. Die gingivalen Lappen wurden so präpariert, dass sie die e-PTFE Membran und Zähne bedeckten und vernäht. Die Tiere wurden 8 Wochen nach der Operation getötet und für histologische Untersuchungen vorbereitet. Ergebnisse: Die Heilung war komplikationslos ohne Exposition der Membran. Die neue Knochenbildung betrug durchschnittlich (±SD) 4.7±0.2 mm (98%) und 4.5±0.4 mm (94%) der Defekthöhe für die Quadranten, die rhBMP-2/ACS mit der e-PTFE Membran erhielten oder rhBMP-2/ACS allein (p>0,05). Im Kontrast dazu war das regenerierte Knochenfeld signifikant erweitert bei den Kieferquadranten, die rhBMP-2/ACS mit e-PTFE Membran erhielten im Vergleich zu denjenigen mit rhBMP-2/ACS allein (9.3±2.7 vs. 5.1±1.1 mm2; p<0.05). Die Zementbildung war in beiden Behandlungsgruppen ähnlich. Ankylosen gefährdeten die parodontalen Regeneration in allen Flächen. Schlussfolgerungen: Die Ergebnisse zeigen, dass die neue makroporöse Platzhalter e-PTFE Membran als Schablone nützlich ist, um die rhBMP-2/ACS induzierte alveoläre Knochenbildung zu betonen. Résumé Contexte: Des technologies utilisant la protéine-2 osseuse morphogénétique humaine recombinée (rhBMP-2) ont montré qu'elle permettait d'augmenter significativement la formation d'os alvéolaire. Les limites du biomatériel (vecteur), cependant, ont restreint leur potentiel biologique aux indications pour lesquels des forces compressives pourraient limiter le volume d'os en formation. L'objectif de cette étude fut d'évaluer le potentiel d'un dispositif en ePTFE macro-poreux permettant de créer un espace pour définir la formation d'os alvéolaire induit par la rhBMP-2 en utilisant un modèle discriminatoire de lésion. Méthodes: Des lésions parodontales supra-alvéolaires de taille critique, 5,6 mm, furent créées autour des troisièmes et quatrièmes prémolaires chez 4 Labrador adultes. Chaque quadrant a été traité par des éponges de collagène résorbables utilisé comme vecteur (ASC) contenant rhBMP-2 (0.4 mg). Les quadrants contralatéraux des animaux furent aléatoirement distribués pour recevoir (ou pas) en plus un dispositif macro-poreux en ePTFE, en forme de dôme sur les implants de rhBMP-2/ACS. Les lambeaux furent déplacés pour recouvrir le dispositif en ePTFE et les dents et suturés. Les animaux furent sacrifiés après 8 semaines pour fournir des observations histologiques de la cicatrisation. Résultats: La cicatrisation ne posait pas de problèmes et on ne nota pas d'exposition des dispositifs. La moyenne de la formation osseuse était de (±SD) 4.7±0.2 mm (98%) et 4.5±0.4 mm (94%) de la hauteur de la lésion, respectivement, pour les quadrants ayant été traités par la rhBMP-2/ACS avec le dispositif en ePTFE ou la rhBMP-2/ACS seule (p>0.05). A l'inverse, la surface osseuse régénérée était significativement plus importante dans les quadrants traités par la rhBMP-2/ACS et les dispositifs en ePTFE par rapport au site traités seulement par la rhBMP-2/ACS (9.3±2.7 vs. 5.1±1.1 mm2; p<0.05). La formation cémentaire était similaire pour les deux groupes de traitement. L'ankylose compromettait la régénération parodontale dans tous les sites. Conclusions: Ces résultats suggèrent que le dispositif en ePTFE macro-poreux, qui assure un espace, semble convenir comme standard pour définir la formation osseuse induite par la rhBMP-2/ACS. [source] Recombinant human bone morphogenetic protein-7 in maxillary sinus floor elevation surgery in 3 patients compared to autogenous bone graftsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 9 2000A clinical pilot study Abstract Background/Aims: This pilot study was designed to determine the clinical bone formation ability of a human recombinant DNA bone morphogenetic protein-7, also referred to as Osteogenic Protein-1 [OP-1] combined with a collagen carrier, implanted in the maxillary sinus of 3 patients. The results were compared with a group of 3 patients treated with sinus floor elevation and autogenous bonegrafts. Methods: 6 consecutive patients, 4 female and 2 male, between 48 and 57 years of age were treated by means of sinus floor elevation for insufficient bone height in the posterior maxilla for implant surgery. 3 patients, 2 female and 1 male, were treated with OP-1 attached to a collagen device. In these patients, 4 maxillary sinus grafting procedures according to Tatum's method were carried out. 1 g of collagen carrier containing 2.5 mg rhOP-1 mixed with 3 ml of saline was placed between the bony floor and the elevated mucosal lining of the most caudal part of the maxillary sinus, in order to increase the vertical bone dimension to place dental implants of a sufficient length. The 3 other patients, also 2 female and 1 male, with a total of 5 sinus sites, were treated with sinus floor elevation and autogenous iliac crest bonegrafts. After 6 months, during dental implant preparation, bone cores were taken for histology. Thus, clinical, radiological and histological results of the 2 groups of 3 patients were compared. Results: 6 months after sinus grafting with OP-1, in 1 male, well-vascularized bonelike tissue of good quality was observed clinically. This could be confirmed by histology. In the second, female, patient no bone formation was observed at all. A cyst-like granular tissue mass, without purulent content, was removed. In the 3rd, female, patient, who received bilateral sinus grafts, some bonelike formation was seen, however it showed flexible tissue which led to the decision that at 6 months after the sinus grafting, the implant placement had to be postponed. In all 5 autogenous grafted sinuses a bone appearance similar to normal maxillary bone was observed clinically as well as histologically and dental implants could be placed six months after sinus floor elevation surgery. Conclusions: These findings indicate that the OP-1 device has the potential for initiating bone formation in the human maxillary sinus within 6 months after a sinus floor elevation operation. However, the various findings in these 3 patients indicate that the behaviour of the material is at this moment insufficiently predictable, in this indication area. Further investigation is indicated before OP-1 can be successfully used instead of the "gold standard" autogenous bone graft. [source] Recombinant human bone morphogenetic protein-4 (rhBMP-4) enhanced posterior spinal fusion without decorticationJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2010Xia Guo No abstract is available for this article. [source] Enhancement of posterolateral lumbar spine fusion using low-dose rhBMP-2 and cultured marrow stromal cellsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2009Tsai-Sheng Fu Abstract We tested the hypothesis that the dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) required to induce spine fusion can be reduced by combination with mesenchymal stem cells (MSCs). Twenty-four adult rabbits underwent posterolateral intertransverse fusion at the L4,L5 level. The animals were divided into four groups based on the implant material: autologous iliac graft, Alginate-MSCs composite, Alginate-BMP-2-MSCs composite, and Alginate-BMP-2 composite. After 16 weeks, the rabbits were euthanized for radiographic examination, manual palpation, biomechanical testing, and histology. Radiographic union of 12 intertransverse fusion areas for the autogenous iliac graft, Alginate-MSCs, Alginate-BMP-2-MSCs, and Alginate-BMP-2 groups was 11, 8, 11, and 0, respectively. Moreover, manual palpation of six fusion segments in each subgroup found solid union to be 6, 1, 5, and 0, respectively. The average torques at failure of the first three groups were 2278,±,135, 1943,±,140, and 2334,±,187 N-mm, respectively. The failure torque did not differ significantly between the autograft and Alginate-BMP-2-MSCs groups; both groups were significantly higher than the Alginate-MSCs group. The results indicate that MSCs delivered with in vitro cellular doses of rhBMP-2 are more osteoinductive than MSCs without rhBMP-2. In combination with MSCs, a low dose (2.5 µg) of rh-BMP-2 could enhance bone formation and posterolateral spine fusion success in the rabbit model. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:380,384, 2009 [source] Generation of tendon-to-bone interface "enthesis" with use of recombinant BMP-2 in a rabbit modelJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 11 2007Yusuke Hashimoto Abstract The anatomical structure at bone-tendon and bone-ligament interfaces is called the enthesis. Histologically, the enthesis is characterized by a transitional series of tissue layers from the end of the tendon to bone, including tendon, fibrocartilage, calcified fibrocartilage, and bone. This arrangement yields stronger direct connection of the soft tissues to bone. In surgical repair, the enthesis has proven difficult to reproduce, and the success of ligament-bone bonding has depended on the fibrous attachment that forms after any ligament reconstructions. In this study, we attempted to generate a direct-insertion enthesis in two stages. First, recombinant human bone morphogenetic protein-2 (rhBMP-2) was injected into the flexor digitorum communis tendon in the rabbit hind limb to induce ectopic ossicle formation. In a second step, the resultant tendon/ossicle complex was then surgically transferred onto the surface of the rabbit tibia to generate a stable tendon-bone junction. One month following surgery, histomorphological examination confirmed direct insertion of tendon-bone structures in the proximal tibia of the rabbit. Ultimate failure loads of the BMP-2-generated tendon-bone junction were significantly higher than in the control group (p,<,0.01). These findings suggest that it is possible to successfully regenerate a direct tendon-to-bone enthesis. Use of this approach may enable successful reconstruction of joints rendered unstable after ligamentous rupture or laxity after anterior cruciate ligament injury. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1415,1424, 2007 [source] Retention of 125I-labeled recombinant human bone morphogenetic protein-2 by biphasic calcium phosphate or a composite sponge in a rabbit posterolateral spine arthrodesis modelJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2002John Louis-Ugbo The purpose of this study was to characterize the retention kinetics of recombinant human bone morphogenetic protein-2 (rhBMP-2) applied to two calcium-based delivery matrices. Biphasic calcium phosphate (BCP) and a composite containing BCP in an absorbable collagen sponge (BCP/ACS) were evaluated using a spinal fusion model in rabbits. rhBMP-2 labeled with radioactive iodine (125I) was used as a tracer to assess in vivo retention of rhBMP-2 in the presence of these materials (nine animals per material studied). Over a 36 day study period, animals were assessed for the following: percent administered dose retained at the implant site as measured by scintigraphic imaging (counting) with a gamma camera (all animals), radiography of the implant site (all animals), radioactivity in blood and plasma (all animals), and radioactivity in the urine and feces (three animals for each material). Radioactivity data were corrected for the decay of 125I and the attenuation between the implant in vivo and the gamma camera. Differences observed between the two materials for the area under the retention vs. time profile (AUC; 988%day for BCP vs. 1070%day for BCP/ACS, p = 0.57) and the mean residence time (MRT; 10.2 days for BCP vs. 7.6 days for BCP/ACS, p = 0.06) were not statistically significant. Initial retention/incorporation of rhBMP-2 was slightly higher for rhBMP-2/BCP/ACS than for rhBMP-2/BCP (96.8% vs. 86.0%, p lt; 0.05). Animals receiving rhBMP-2/BCP showed a longer terminal retention half-life (t1/2) than did those receiving rhBMP-2/BCP/ACS (7.5 vs. 4.5 days, p < 0.05). The urinary radioactivity recovery data supported the data obtained by scintigraphy. Over the 36 day collection period, essentially complete recovery of radioactivity (dose) in urine was observed for rhBMP-2/BCP and rhBMP-2/BCP/ACS and the majority of the radioactivity (approximately 95%) was soluble in trichloroacetic acid, suggesting extensive catabolism of rhBMP-2 before renal excretion. Fecal recovery of radioactivity was low, approximately 2,3%. In conclusion, rhBMP-2 was retained at the implant site when delivered with either BCP or BCP/ACS based on mean residence time and area under the retention curve vs. time profile. Use of these matrices resulted in detectable rhBMP-2 levels at the surgical site for over a week in contrast to data reported with several other matrices that lasted less time. Systemic catabolism and elimination of the rhBMP-2 was extensive and systemic presence of the protein was negligible. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Formation and resolution of ankylosis under application of recombinant human bone morphogenetic protein-2 (rhBMP-2) to class III furcation defects in catsJOURNAL OF PERIODONTAL RESEARCH, Issue 4 2005D. Takahashi 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 µg rhBMP-2/mm3 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. [source] Enhancement of bone healing using non-glycosylated rhBMP-2 released from a fibrin matrix in dogs and catsJOURNAL OF SMALL ANIMAL PRACTICE, Issue 1 2005H. G. Schmoekel Objectives: To test a non-glycosylated recombinant human bone morphogenetic protein-2 (ngly-rhBMP-2)/fibrin composite, which has been shown experimentally to enhance healing of bone defects in rodents, in a clinical case series of dogs and cats undergoing treatment for fracture non-unions and arthrodesis. Methods: A ngly-rhBMP-2/fibrin composite was applied in 41 sites in 38 dogs and cats for which a cancellous bone autograft was indicated, replacing the graft. Results: Bridging of the bone defect with functional bone healing was achieved in 90 per cent of the arthrodesis and fracture nonunions treated in this manner. Clinical Significance: This prospective clinical study demonstrates the beneficial effects of ngly-rhBMP-2 in a specially designed fibrin matrix on the treatment of bone defects, and validates the use of this composite as an alternative to bone autografts in dogs and cats. [source] Three-dimensional fibrous PLGA/HAp composite scaffold for BMP-2 deliveryBIOTECHNOLOGY & BIOENGINEERING, Issue 1 2008Hemin Nie Abstract A protein loaded three-dimensional scaffold can be used for protein delivery and bone tissue regeneration. The main objective of this project was to develop recombinant human bone morphogenetic protein-2 (rhBMP-2) loaded poly(D,L -lactide-co-glycolide)/hydroxylapatite (PLGA/HAp) composite fibrous scaffolds through a promising fabrication technique, electrospinning. In vitro release of BMP-2 from these scaffolds, and the attachment ability and viability of marrow derived messenchymal stem cells (MSCs) in the presence of the scaffolds were investigated. The PLGA/HAp composite scaffolds developed in this study exhibit good morphology and it was observed that HAp nanoparticles were homogeneously dispersed inside PLGA matrix within the scaffold. The composite scaffolds allowed sustained (2,8 weeks) release of BMP-2 whose release rate was accelerated with increasing HAp content. It was also shown that BMP-2 protein successfully maintained its integrity and natural conformations after undergoing the process of electrospinning. Cell culture experiments showed that the encapsulation of HAp could enhance cell attachment to scaffolds and lower cytotoxicity. Biotechnol. Bioeng. 2008;99: 223,234. © 2007 Wiley Periodicals, Inc. [source] A randomized-controlled clinical trial evaluating clinical and radiological outcomes after 3 and 5 years of dental implants placed in bone regenerated by means of GBR techniques with or without the addition of BMP-2CLINICAL ORAL IMPLANTS RESEARCH, Issue 7 2009Ronald E. Jung Abstract Objective: The aim of this randomized-controlled clinical trial was to evaluate the long-term outcome of implants placed in bone augmented with a xenogenic bone substitute material and a collagen membrane with or without the addition of recombinant human bone morphogenetic protein-2 (rhBMP-2). Material and methods: Eleven patients received a total of 34 implants placed into sites exhibiting lateral bone defects. In a split mouth design, the defects were randomly treated with the graft material and the collagen membrane either with (test) or without (control) rhBMP-2. The patients were examined 3 and 5 years after insertion of the prosthetic restoration. Student's paired t -test was performed to detect differences between the two groups. Results: The survival rate at 3 and 5 years was 100% for both groups. The peri-implant soft tissues were stable and healthy without any difference between the two groups. The prosthetic reevaluation demonstrated four loose prosthetic screws during the first 3 years and seven ceramic chippings after 3 and 5 years. The mean distance between the first bone to implant contact to implant abutment junction at 3 years was 1.37 mm (test), 1.22 mm (control), and 1.38 mm (test), and 1.23 mm (control) at 5 years. The difference of <0.2 mm between test and control implants was not statistically significant. The mean change of the marginal bone level between baseline and 5 years ranged from ,0.07 mm (mesial, test), ,0.11 mm (distal, test), ,0.03 mm (mesial, control), to +0.13 mm (distal, control). No statistically significant differences were observed between test and control sites. Conclusion: Implants placed in bone augmented with and without rhBMP-2 revealed excellent clinical and radiological outcomes after 3 and 5 years. [source] Effect of recombinant human bone morphogenetic protein-7 (rhBMP-7) on the viability, proliferation and differentiation of osteoblast-like cells cultured on a chemically modified titanium surfaceCLINICAL ORAL IMPLANTS RESEARCH, Issue 5 2009Adriane Y. Togashi Abstract Aim: The aim of the present study was to assess the influence of the chemical characteristics and roughness of titanium surfaces on the viability, proliferation and differentiation of osteoblast-like cells cultured in a medium supplemented with recombinant human bone morphogenetic protein-7 (rhBMP-7). Material and methods: Osteo-1 cells were grown on titanium disks presenting with the following surfaces: (1) machined, (2) coarse grit-blasted and acid-attacked (SLA) and (3) chemically modified SLA (SLAmod) in the absence or presence of 20 ng/ml rhBMP-7 in culture medium. The viability and number of osteo-1 cells were evaluated after 24 h. Analyses of total protein content (TP) and alkaline phosphatase (AP) activity at 7, 14 and 21 days, collagen content at 7 and 21 days and mineralized matrix formation at 21 days were performed. Results: Cell viability (P=0.5516), cell number (P=0.3485), collagen content (P=0.1165) and mineralized matrix formation (P=0.5319) were not affected by the different surface configurations or by the addition of rhBMP-7 to the medium. Osteo-1 cells cultured on SLA surfaces showed a significant increase in TP at 21 days. The ALPase/TP ratio (P=0.00001) was affected by treatment and time. Conclusion: The results suggest that the addition of rhBMP-7 to the culture medium did not exert any effect on the viability, proliferation or differentiation of osteoblast-like cells grown on the different surfaces tested. All titanium surfaces analyzed allowed the complete expression of the osteoblast phenotype such as matrix mineralization by osteo-1 cells. [source] Bone augmentation by onlay implant using recombinant human BMP-2 and collagen on adult rat skull without periosteumCLINICAL ORAL IMPLANTS RESEARCH, Issue 4 2000Masaru Murata The purpose of this study was to determine whether bone augmentation could be obtained by the composite of recombinant human bone morphogenetic protein-2 (rhBMP-2) and bioabsorbable atelocollagen when the periosteum was resected, and to compare the efficacy of the rhBMP-2/collagen implant and the collagen alone implant. The onlay implant was inserted into the space between the elevated galea aponeurotica and the skull without the periosteum of 10-month-old rats. The rhBMP-2/collagen implant resulted in osteoblasts differentiation under the galea at 1 week and active bone formation without a prior formation of cartilage. At 4 weeks, the bony trabeculae were interconnected and connected directly with the compact bone of the skull. Histomorphometric analysis at 4 weeks demonstrated that the rhBMP-2/collagen implant showed 92.5% in the volume of bone tissue, whereas the collagen alone showed 0%. The implanted collagen was gradually replaced by bone tissue in the presence of rhBMP-2. Our present results indicate that rhBMP-2 stimulates undifferentiated mesenchymal cells in the galea overlying the implant to proliferate and differentiate directly into osteoblasts on the carrier collagen fibers. The collagen matrix was stably placed on the skull and suitable as a substitute for rhBMP-2. The rhBMP-2/collagen onlay implant might be clinically applicable for bone augmentation even under the condition without the periosteum. [source] | |||||||||||||