Horizontal ridge augmentation of a single atrophic site in the anterior maxilla using hydroxyapatite and rhBMP-2 / Augmento óseo horizontal de reborde alveolar en sitio atrófico único en maxila anterior usando hidroxiapatita y rhBMP-2

SUMMARY: Bone morphogenetic protein (rhBMP-2) is a powerful osteo-inductive growth factor widely used in bone reconstruction and both the vehicle used to administer it and the scaffold substrate could determine its success in clinical situations. The aim was to analyse the clinical behaviour of dental implants placed in single alveolar ridges with a horizontal deficiency in the maxillary anterior region that were reconstructed horizontally with rhBMP-2 and porous hydroxyapatite (HA). Inclusion criteria were both males and females, between the ages of 18 and 29 with single tooth loss of one upper incisor. Cone Beam Computed Tomography (CBCT) was used to take measurements prior to bone augmentation and again prior to the implant insertion. Surgery was carried out under local anaesthetic. In the primary procedure, bone substitute was introduced using porous HA and rhBMP-2; after 4 to 5 months, dental implant surgery was carried out and the implant placed; after 3 months of consolidation the provisional prosthesis was placed and then a definitive restoration was placed. Variables were analysed using the t-test with a p-value of < 0.05 in order to assess statistical significance. Thirteen subjects were included (6 females and 7 males). Bone augmentation resulted in a bone gain of 4.15mm (p=0.023), which was shown to be statistically significant. All of the grafts placed were successful and 13 implants were placed, using torques between 30 and 70N, without complications. For the final prostheses, 11 were screw retained and 2 were cemented in place. The horizontal bone augmentation using HA and rhBMP-2 is an efficient technique for single bone defects in the anterior maxillary area; clinical trials on a larger scale are needed to confirm these results.

RESUMEN: La proteína ósea morfogenética (BMP-2) es un potente osteoinductor utilizado ampliamente en técnicas reconstructivas; el vehículo de instalación es determinante en su evolución. El objetivo fue analizar el comportamiento clínico de implantes dentales instalados en rebordes alveolares únicos con deficiencia horizontal del sector anterior reconstruida horizontalmente con BMP-2 e hidroxiapatita (HA) porosa. Fueron incluidos sujetos de ambos sexos de entre 18 y 29 años, con pérdida dentaria unitaria a nivel de incisivos superiores. Se utilizó tomografía computadorizada para realizar mediciones en las etapas previa a la instalación del injerto y previo a la instalación del implante. Las cirugías fueron realizadas bajo anestesia local. En la primera intervención se realizó la instalación del injerto óseo utilizando HA porosa y BMP-2; después de 4 a 5 meses se realizó la instalación del implante dental; 3 meses después se realizó la conexión protésica y rehabilitación final. Las variables fueron estudiadas con la prueba t test considerando el valor de p< 0,05 para considerar significancia estadística. Trece sujetos fueron incluidos (6 mujeres y 7 hombres); con la reconstrucción ósea se obtuvo una ganancia ósea de 4,15mm (p=0.023) que fue estadísticamente significativo. No existió pérdida en ningún injerto realizado; se instalaron 13 implantes con torques entre 30 y 70N sin complicaciones; se realizaron prótesis fijas atornilladas en 11 casos y cementadas en 2 casos. La técnica con HA y BMP- 2 es eficiente para reconstruir defectos horizontales en perdidas unitarias del sector anterior maxilar; ensayos clínicos de mayor escala son necesarios para confirmar estos resultados.

Influencia de rhBMP-2 en la reparación ósea de defectos críticos con diferentes biomateriales / Influence of rhBMP-2 on bone repair of critical size defects with different biomaterials

La regeneración de defectos óseos críticos requiere la utilización de biomateriales óseos. Así, se han utilizados agentes osteogénicos como la proteína morfogenética (rhBMP-2). El objetivo fue describir la formación ósea de defectos óseos críticos en calota de ratas utilizando rhBMP-2 con distintos biomateriales. Se realizaron dos defectos óseos críticos de 5 mm en 15 calotas de ratas machos adultas divididos en grupo control (sin tratamiento) (C); autoinjerto + rhBMP-2 (A); fosfato tricálcico + rhBMP-2 (BTCP); xenoinjerto de bovino + rhBMP-2 (B) y hidroxihapatita + rhBMP-2 (HA). A las ocho semanas post tratamiento, se realizó la eutanasia y posterior análisis histológico de los defectos. El grupo C no presentó formación de tejido óseo en el defecto. En el resto de los grupos, se formó abundante tejido óseo en los márgenes, por lo tanto, el defecto presentó menor tamaño. El grupo HA presentó formación ósea trabecular con amplios espacios medulares y abundante tejido adiposo. El grupo B-TCP también presentó formación ósea trabecular y la mayoría de las muestras presentaron puente óseo en el defecto. El grupo B presentó partículas de material injertado rodeado por trabéculas óseas y tejido conectivo. En el grupo A, todas las muestras presentaban puente óseo formado por bloques de autoinjerto rodeado por tejido conectivo y óseo. Es posible concluir que los defectos óseos de 5 mm en calota de rata son defectos críticos que requieren utilizar biomateriales para la reparación del defecto. El grupo B-TCP presentó características histológicas más próximas a la regeneración ósea lograda con el Grupo A.

The regeneration of bone critical size defects requires the use of bone biomaterials. Therefore, an osteogenic agent such as bone morphogenetic protein (rhBMP-2) has been used. The objective was to describe the bone formation of bone critical size defects in the rat calvaria using rhBMP-2 with different biomaterials. Two critical bone defects of 5 mm were made in 15 calvaria of adult male rats divided into a control group (without treatment) (C); autograft + rhBMP-2 (A); tricalcium phosphate + rhBMP-2 (B-TCP); bovine xenograft + rhBMP-2 (B) and hydroxyhapatite + rhBMP-2 (HA). At eight weeks post treatment, euthanasia and subsequent histological analysis of the defects were performed. Group C did not show bone tissue formation in the defect. In the rest of the groups, abundant bone tissue formed in the margins, therefore, the defect was smaller. The HA group presented trabecular bone formation with large medullary spaces and abundant adipose tissue. The B-TCP group also presented trabecular bone formation and most of the samples formed a bone bridge across the defect. Group B presented grafted material particles surrounded by bone trabeculae and connective tissue. In group A, all samples presented a bone bridge formed by autograft blocks surrounded by connective and bone tissue. It is possible to conclude that 5 mm bone defects in rat calvaria are critical size defects that require the use of biomaterials for defect repair. The B-TCP group presented histological characteristics similar to the bone regeneration achieved with Group A.

Calcium hydrogen phosphate dehydrate combined with gelatin and recombinant human bone morphologic protein 2/7 for repair of bone defects in rabbits / 中国组织工程研究

BACKGROUND: Studies have shown that the osteogenic ability of 10% strontium-doped calcium hydrogen phosphate dihydrate is higher than that of calcium hydrogen phosphate dihydrate and 5% strontium-doped calcium hydrogen phosphate dihydrate, but also found that the pore structure of 10% strontium-doped calcium hydrogenphosphate dihydrate is not ideal, and the early osteogenic effect is not satisfactory. OBJECTIVE: To investigate the osteogenic effect of the composite of 10% strontium-doped calcium hydrogenphosphate dehydrate and gelatin and recombinant human bone morphogenetic protein 2/7 (rhBMP2/7). METHODS: Gelatin-10% strontium-doped calcium hydrogenphosphate dihydrate and gelatin-10% strontium-doped calcium hydrogenphosphate dihydrate material containing 0.04 g/L and 1 g/L rhBMP2/7 were prepared respectively. Forty-five rabbit models of bilateral mandibular defects were prepared and then divided into five groups. In the blank control group, no material was implanted. 10% strontium-doped calcium hydrogen phosphate dihydrate (control group) and gelatin-10% strontium-doped calcium hydrogen phosphate dihydrate (gelatin group), 0.04 g/L rhBMP2/7-gelatin-10% strontium-doped calcium hydrogenphosphate dihydrate (0.04 g/L rhBMP2/7 group), and 1 g/L rhBMP2/7-gelatin-10% strontium-doped calcium hydrogenphosphate dihydrate (1 g/L rhBMP2/7 group) were implanted in the remaining four groups, respectively. Bone defect specimens were taken at 4, 8 and 12 weeks after surgery, and were examined by cone beam CT and immunohistochemistry. This study was approved by the Animal Ethics Committee of North China University of Science and Technology, China. RESULTS AND CONCLUSION: Cone beam CT examination revealed that at 8 weeks after surgery, bone repair was basically completed and the new bone tissue was almost fused with the surrounding tissue in the 1 g/L rhBMP2/7 group. Most of defect area was repaired, and the edge of new bone was unsmooth in the 0.04 g/L rhBMP2/7 and gelatin groups. Bone defect in the control group partially repaired. At 12 weeks after surgery, bone repair was completed in the gelatin, 0.04 rhBMP2/7 and 1 g/L rhBMP2/7 groups. Immunohistochemistry revealed that at 4 and 8 weeks after surgery, type I collagen expression in the 1 g/L rhBMP2/7 group was significantly higher than that in the other four groups (P 0.05). These results suggest that the addition of gelatin and 1 g/L rhBMP2/7 to 10% strontium-doped calcium hydrogenphosphate dihydrate can promote the repair of bone defects.

Effect of rhBMP-2 and Chitosan in Differentiation of Periodontal Ligament Stem Cells into an Osteoblastic Lineage

Aims: To analyze the effect of rhBMP-2 and Chitosan in differentiation of Periodontal Ligament Stem Cells (PDLC) into an osteoblastic lineage. Study Design: This study was designed as in vitro study and osteogenic biomarkers were determined in the culture supernatant. Place and Duration of Study: Laboratory of Oral Biology Faculty of Dentistry Universitas Indonesia. Jakarta 10430 Indonesia, January – September 2016. Methodology: Human periodontal ligament stem cells (PDLC) were isolated from the root of vital teeth, followed by identification of stem cells by antibody anti  STRO-1. Chitosan was used at the concentration of 0.15%.  The culture cells were divided into four groups as follow, the control group (PDLC) and treatment groups with recombinant human Bone Morphogenic protein 2 (rhBMP-2), the combination chitosan-rhBMP-2 and chitosan only. The levels of alkaline phosphatase (ALP) was determined by colorimetry and osteocalcin and collagen type I were measured using ELISA. Results: The results showed that levels of ALP tended to increase is in all groups. At day 14, the highest levels of ALP was in chitosan treated group. The concentration of collagen type 1 managed to raise is in all groups on days 14, and the highest levels Collagen type 1 occurred in RH BMP-2 and chitosan treated cells, after that decrease in all groups until day 21(p < 0.05).  Osteocalcin concentration tended to increase is in all groups, and at days 21, the highest levels in with rhBMP-2 + chitosan.   Conclusion: The rhBMP-2, chitosan, and its combination induce differentiation of periodontal ligament stem cells into the osteoblastic lineage.

Osteogenic potential of recombinant human bone morphogenetic protein-2 combined with Bio-oss bone substitute in implant restorations in anterior esthetic region / 口腔疾病防治

Objective@#To study the osteogenic potential of recombinant human bone morphogenetic protein 2 (rhBMP-2) combined with Bio-oss bone substitute in the implant restoration of bone defects in the anterior esthetic region. @*Methods@# Twelve patients who underwent the immediate placement of 20 implants with a bone augmentation procedure using rhBMP-2 and Bio-oss were included in this study. Changes in the height and thickness of the buccal bone over 6 months were measured, and the soft tissue was evaluated using the pink esthetic score (PES) after crown placement. @*Results@# All 20 implants were successfully osseointegrated, and the average increase in bone height was 1.9 mm; different degrees of bone height growth were observed for 17 (85%) implants sites. In one case, there was a severe bone fracture on the buccal side before the operation, resulting in bone plate resorption and decreased alveolar bone height. The bone height did not change significantly in 2 cases. The thickness of the buccal bone plate for all implants was greater than 1 mm. The average thickness was 1.9 mm, and the average PES was 9.8 points. @*Conclusion@# rhBMP-2 combined with Bio-oss bone substitute has a preferable effect on the restoration of bone defects in the anterior esthetic area, and can achieve good aesthetic effect.

Proteína morfogenética ósea y su opción como tratamiento de la fisura alveolar / Bone morphogenetic protein and its option as an alveolar cleft treatment

La proteína morfogenética ósea (BMP), es una proteína endógena que ha mostrado efectos significativos en la promoción de la formación ósea. El uso de BMP ha sido descrito en la reconstrucción de defectos óseos de origen traumáticos y patológicos, incluyendo la fisura alveolar, el aumento de reborde alveolar, la elevación de seno maxilar, el injerto de alveolo post-extracción, y la cirugía perimplantaria entre otros. A pesar de las ventajas asociadas al uso de BMP y que en la actualidad se aplica en combinación con matrices de colágeno, ciertas propiedades tales como su baja resistencia mecánica y su elevada tasa de liberación inicial disminuyen su eficacia en la formación ósea. En este contexto, el desarrollo de nuevos sistemas de liberación prolongada de BMP que permitan la quimiotaxis de células mesenquimáticas y su posterior diferenciación a osteoblastos representa un desafío con alto potencial clínico para la estimulación de la formación ósea. En este trabajo, se describe el uso de BMP en la reconstrucción de fisuras alveolares y en particular se discuten las ventajas de su administración en micropartículas poliméricas comosistemas de liberación de BMP (rhBMP-2) con promisorias aplicaciones en la estimulación de la formación ósea.

Bone morphogenetic protein (BMP) is an endogenous protein that has shown significant effects in the promotion of bone formation. BMP also has been described in the reconstruction of traumatic and pathological bone defects, including alveolar cleft, alveolar ridge augmentation, maxillary sinus elevation, and applications in post-extraction alveolus graft, and peri-implant surgery among others. Despite the advantages associated with the use of BMP, currently is applied in combination with collagen matrices, which has certain properties such as low mechanical resistance and a high burst initial release that diminish its effectiveness in bone formation. In this context, the development of novel systems with greater mechanical resistance and prolonged release of BMP, that lead to chemotaxis of mesenchymal cells, following by its differentiation to osteoblasts represents a major challenge that holds outstanding clinical potential for the stimulation of bone formation. In this paper, we describe the use of BMP for the reconstruction of alveolar clefts, and its advantages being administrated in polymeric microparticles as sustain release system with promising applications in the stimulation of bone formation.

Ultrasound evaluation in recombinant human bonemorphogenic protein-2 ( rhBMP-2 ) artificial bone angiogenesis / 中华超声影像学杂志

Objective To evaluate the application value of ultrasound in vascularization of different artificial bones . Methods A total of 15 New Zealand rabbits were utilized for model establishment of classic segmental bone defect in bilateral radius . Recombinant human bonemorphogenic protein-2 ( rhBMP-2 ) coralline hydroxyapatite(CHA) and CHA were implanted into left and right limbs . Each CHA was divided into 4 equal parts which were examined with conventional ultrasonography and contrast-enhanced ultrasonography( CEUS ) on 3 d ,7 d ,11 d ,15 d ,30 d and 45 d respectively . CEUS quantitative was performed by time-intensity curve(TIC) ,which parameters including the basic intensity(BI) ,peak intensity (PI) ,increased signal intensity ( ΔSI) and time to peak ( TTP) . Then the results were analyzed and compared to pathology . Results Within the same duration ,the vascularization degree in rhBMP-2 group was stronger than that in the ordinary group with advanced vascularization time . Positive correlation was detected between ΔSI and time of both groups ( r =0 .938 ,0 .890 ;P =0 .000) ,and negative correlation was found between BI/PI or TTP and time ( BI/PI: r = -0 .798 ,-0 .899 ; P = 0 .000 ;TTP= r -0 .874 ,-0 .868 ;P = 0 .000 ) . No statistical significance was observed among four observation points of both CHA ,which indicated no obvious difference in vascularization degree of each observation point . Conclusions The structure of bone graft can be clearly displayed by conventional ultrasound ,and CEUS is able to show the early blood perfusion in two CHA grafts and to accurately evaluate the difference of CHA microvascular growth before and after rhBMP-2 application . The combination of these two techniques is a promising approach of evaluating bone graft vascularization in clinical practice .

Development of Refolding Process to Obtain Active Recombinant Human Bone Morphogenetic Protein-2 and its Osteogenic Efficacy on Oral Stem Cells

BMP-2 is a well-known TGF-beta related growth factor, having a significant role in bone and cartilage formation. It has been employed to promote bone formation in some clinical trials, and to differentiate mesenchymal stem cells into osteoblasts. However, it is difficult to obtain this protein in its soluble and active form. hBMP-2 is expressed as an inclusion body in the bacterial system. To continuously supply hBMP-2 for research, we optimized the refolding of recombinant hBMP-2 expressed in E. coli, and established an efficient method by using detergent and alkali. Using a heparin column, the recombinant hBMP-2 was purified with the correct refolding. Although combinatorial refolding remarkably enhanced the solubility of the inclusion body, a higher yield of active dimer form of hBMP-2 was obtained from one-step refolding with detergent. The refolded recombinant hBMP-2 induced alkaline phosphatase activity in mouse myoblasts, at ED₅₀ of 300-480ng/ml. Furthermore, the expressions of osteogenic markers were upregulated in hPDLSCs and hDPSCs. Therefore, using the process described in this study, the refolded hBMP-2 might be cost-effectively useful for various differentiation experiments in a laboratory.

Double-layer nanoparticles loaded with rhBMP-2 and SDF-1:Preparation,characterization and drug re-lease in vitro / 实用口腔医学杂志

Objective:To construct double-layered controlled release system containing SDF-1 and rhBMP-2 molecules and to study the release profile of the system in vitro.Methods:The polylactic acid/chitosan(PLA/CS)nanoparticles were prepared with “emulsification-solution evaporation method”,the preparation parameters were determined by orthogonal test design.The particle size was observed by nanoparticle size analyzer,the morphology of the nanoparticles was observed with electron microscope.Then rhBMP-2 and SDF-1 were loaded into the nanoparticles in the process of emulsification,the loading efficiency and encapsulation efficiency were calculated and in vitro release was observed.Results:The double-layer nanoparticles showed spherical geometry,smooth surface and complete separation. The average particle size of the nanoparticles was (542.33 ±14.38)nm;The drug loading and incorporation efficiency of rhBMP-2 were (82.41 ±1.05)% and (24.67 ±0.43)ng/mg,those of rhBMP-2 were (75.58 ±0.84)% and (22.63 ±0.41)ng/mg,respectively. The release time of the drug from the system sustained over at least 30 days,the release profile of both drugs showed “biphasic release”. The cumulative release rate of SDF-1 and rhBMP-2 was 72.85% and 91.01% in 30 days respectively.Conclusion:The SDF-1 and rh-BMP-2 loaded PLA/CS nanoparticles have excellent morphology,high entrapment and good sustained-release in vitro.

Bone regenerative effect of recombinant human bone morphogenetic protein-2 after cyst enucleation / 대한악안면성형재건외과학회지

BACKGROUND: The aim of this study is to quantitatively evaluate the effect of rhBMP-2 for repair of bone defects after cyst enucleation using the osteogenesis index (OI). METHODS: Under general anesthesia, 10 patients (12 lesions) underwent oral or maxillofacial surgery for cyst enucleation. Postoperatively, 12 lesions were divided into two groups: group A (six lesions) was treated with absorbable collagen sponge (ACS) in combination with rhBMP-2, and group B (six lesions) was treated with ACS alone. After 3 months, cone-beam computed tomographic scans were obtained to measure changes in the volume of the lesions. We then calculated the OI of each group at two different Hounsfield units to determine any statistically significant difference between these two groups (Mann–Whitney U test). RESULTS: As tested at the level of new bone, the mean OI was 72.37% in group A and 55.08% in group B —a statistically significant difference (p=0.041). As tested at the level of mature bone, the mean OI was 27.47% in group A and 18.88% in group B, but the difference was not statistically significant (p=0.394). CONCLUSIONS: The application of rhBMP-2 after maxillofacial cyst enucleation accelerated new bone formation in the bone defects. Thus, the use of rhBMP-2 in combination with ACS may be considered an alternative to conventional bone grafting in some patients with postoperative bone defects. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40902-016-0070-4) contains supplementary material, which is available to authorized users.

Maxillary Reconstruction Using rhBMP-2 and Titanium Mesh: Technical Note About the Use of Stereolithographic Model / Reconstrucción Maxilar Utilizando rhBMP-2 y Malla de Titanio: Nota Técnica sobre el Uso de Modelo Estereolitográfico

Maxillary reconstruction is a common procedure in maxillofacial surgery; for this purpose is used autogenous bone, alloplastic bone or another one with different results. In all of them, traditionally the use of computed tomography is used to make the surgical plan, however, 3D models are not used frequently. This report show a new application of the stereolithography to anticipate the surgical treatment of maxillary reconstruction, using a titanium mesh and rhBMP-2 to obtain a predictable surgical result with diminished surgical time.

La reconstrucción maxilar es un procedimiento común en cirugía maxilofacial; para este propósito es utilizado hueso autógeno, hueso aloplástico u otro tipo de hueso con diferentes resultados. En todos ellos, tradicionalmente el uso de tomografía computadorizada se emplea para elaborar el plan quirúrgico, sin embargo, los modelos 3D no son utilizados con frecuencia. Este reporte presenta una nueva aplicación de la estereolitografia para anticipar el tratamiento quirúrgico de la reconstrucción maxilar, usando una malla de titanio y rhBMP-2 para obtener un resultado quirúrgico predecible con disminución del tiempo quirúrgico.

Bone morphogenetic protein 2 poly lactic acid sustained release microspheres for compatibility between rabbit bone marrow mesenchymal stem cell research / 重庆医学

Objective To investigate the influence of recombinant human bone morphogenetic protein‐2(rhBMP‐2)of poly lactic acid(PLA) release microspheres for compatibility of rabbit bone marrow mesenchymal stem cells(BMSCs) .Methods The rh‐BMP‐2‐PLA release microspheres were prepared by w/o/w multiple emulsion volatilizing method and then cocultured BMSCs .The effects of rhBM P‐2‐PLA release microspheres on the cytotoxicity and relative proliferation rate by MTTassay .Evaluation of mate‐rials biocompatibility by inverted microscope and scanning electron microscope(SEM) .Results The rhBMP‐2‐PLA release micro‐spheres in various concentration of leaching solution and BMSCs training of uninfected cells .Experimental group and control group in 4 different time cell proliferation OD values by analysis of repeated measurement variance between time OD values were statisti‐cally significant(P=0 .000) ,the experimental group and control group OD values are statistically significant(P=0 .025) ,the exper‐imental group higher than the control group ,experimental group OD value time there was a significant interaction effect and the group number ,the change trend are obviously different(P=0 .006) .Inverted microscope to observe materials normal cell prolifera‐tion ,SEM found that vaccination cells surrounding rhBMP‐2‐PLA release microspheres of 7 days later ,the cells grew well and split proliferation activity .Conclusion rhBMP‐2‐PLA release microspheres of BMSCs has non‐toxic and has compatibility .

Biologic Response of Degenerative Living Human Nucleus Pulposus Cells to Treatment with Cytokines

PURPOSE: To investigate the molecular responses of various genes and proteins related to disc degeneration upon treatment with cytokines that affect disc-cell proliferation and phenotype in living human intervertebral discs (IVDs). Responsiveness to these cytokines according to the degree of disc degeneration was also evaluated. MATERIALS AND METHODS: The disc specimens were classified into two groups: group 1 (6 patients) showed mild degeneration of IVDs and group 2 (6 patients) exhibited severe degeneration of IVDs. Gene expression was analyzed after treatment with four cytokines: recombinant human bone morphogenic protein (rhBMP-2), transforming growth factor-beta (TGF-beta), interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha). Molecular responses were assessed after exposure of cells from the IVD specimens to these cytokines via real-time polymerase chain reaction and immunofluorescence staining. RESULTS: mRNA gene expression was significantly greater for aggrecan, type I collagen, type II collagen, alkaline phosphatase, osteocalcin, and Sox9 in group 1 than mRNA gene expression in group 2, when the samples were not treated with cytokines. Analysis of mRNA levels for these molecules after morphogen treatment revealed significant increases in both groups, which were much higher in group 1 than in group 2. The average number of IVD cells that were immunofluorescence stained positive for alkaline phosphatase increased after treatment with rhBMP-2 and TGF-beta in group 1. CONCLUSION: The biologic responsiveness to treatment of rhBMP-2, TGF-beta, TNF-alpha, and IL-1beta in the degenerative living human IVD can be different according to the degree of degeneration of the IVD.

Complications of Anterior Cervical Fusion using a Low-dose Recombinant Human Bone Morphogenetic Protein-2

OBJECTIVE: There are several reports, which documented a high incidence of complications following the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in anterior cervical fusions (ACFs). The objective of this study is to share our experience with low-dose rhBMP-2 in anterior cervical spine. METHODS: We performed a retrospective analysis of 197 patients who underwent anterior cervical fusion (ACF) with the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) during 2007-2012. A low-dose rhBMP-2 (0.7mg/level) sponge was placed exclusively within the cage. In 102 patients demineralized bone matrix (DBM) was filled around the BMP sponge. Incidence and severity of dysphagia was determined by 5 points SWAL-QOL scale. RESULTS: Two patients had prolonged hospitalization due to BMP unrelated causes. Following the discharge, 13.2%(n=26) patients developed dysphagia and 8.6%(n=17) patients complained of neck swelling. More than half of the patients (52.9%, n=9) with neck swelling also had associated dysphagia; however, only 2 of these patients necessitated readmission. Both of these patients responded well to the intravenous dexamethasone. The use of DBM did not affect the incidence and severity of complications (p>0.05). Clinico-radiological evidence of fusion was not observed in 2 patients. CONCLUSION: A low-dose rhBMP-2 in ACFs is not without risk. However, the incidence and severity of complications seem to be lower with low-dose BMP placed exclusively inside the cage. Packing DBM putty around the BMP sponge does not affect the safety profile of rhBMP-2 in ACFs.

Enhancement of Bone Formation by Bone Morphogenetic Protein-2 Released from Poly (L-lactic-co-glycolic acid) Microsphere.

An appropriate carrier acting as a sustained delivery vehicle for bone morphogenetic proteins (BMPs) is required for the maximal clinical effectiveness of these osteogenic proteins to enhance bone formation. The purpose of this study was to evaluate a lowmolecular- weight poly(L-lactic-co-glycolic acid) (PLGA) copolymer as a synthetic, biodegradable carrier for the sustained delivery of bone morphogenetic protein-2 (BMP-2), and then to address the hypothesis that BMP-2 delivery from this vehicle could promote cell proliferation in vitro and ectopic bone formation in vivo. The BMP-2 was entrapped in microspheres of PLGA by using an improved water-in-oil-in water double-emulsionsolvent- extraction technique. The in vitro release kinetics of rhBMP-2 was determined by ELISA. Then we verified the effect of the sustained delivery vehicle on MSC cell proliferation. The ectopic bone induction in intramuscular implants of mice was evaluated at 2 and 4 weeks post-implantation. The results showed the PLGA microsphere released a total of 14.2%±0.71% rhBMP-2 at the initial phase followed by a prolonged release for 28 days. The rhBMP-2 released from the PLGA microsphere stimulated an increase in alkaline phosphatase (ALP) activity of MSC cells for 5 days in vitro, suggesting that the delivery vehicle releases BMP-2 for a prolonged period in an active form. Moreover, the released rhBMP-2 from the PLGA microsphere significantly promoted MSC cells proliferation after days 5 in culture. In vivo bone formation studies showed the rhBMP-2- loaded PLGA microsphere induced ectopic bone formation to a much greater extent than did rhBMP-2 treated mice. These results demonstrated that the PLGA copolymer material is capable of potentiating the osteogenic efficacy of BMP-2 and, as such, represents a promising delivery vehicle for BMP-2 for orthopedic and dental repair.

The Use of Recombinant Human Bone Morphogenic Protein-2 (rhBMP-2) in Treatment for Cysts of the Oral and Maxillofacial Regions

Effect of recombinant human bone morphogenetic protein 2/poly-lactide-co-glycolic acid (rhBMP-2/PLGA) with core decompression on repair of rabbit femoral head necrosis

OBJECTIVE@#To observe the effect of recombinant human bone morphogenetic protein 2/poly-lactide-co-glycolic acid (rhBMP-2/PLGA) with core decompression on repair of rabbit femoral head necrosis.@*METHOD@#Bilateral femoral head necrosis models of rabbit were established by steroid injection. A total of 48 rabbits (96 femoral head necrosis) were randomly divided into 4 groups: Group A, control group with12 rabbits, 24 femoral head necrosis; Group B, treated with rhBMP-2/PLGA implantation after core depression, with 12 rabbits, 24 femoral head necrosis; Group C, treated with rhBMP-2 implantation after core depression, with 12 rabbits, 24 femoral head necrosis; Group D treated with core depression group without implantation, with 12 rabbits, 24 femoral head necrosis. All animals were sacrificed after 12 weeks. The ability of repairing bone defect was evaluated by X-ray radiograph. Bone mineral density analysis of the defect regions were used to evaluate the level of ossification. The morphologic change and bone formation was assessed by HE staining. The angiogenesis was evaluated by VEGF immunohistochemistry.@*RESULTS@#The osteogenetic ability and quality of femoral head necrosis in group B were better than those of other groups after 12 weeks by X-ray radiograph and morphologic investigation. And the angiogenesis in group B was better than other groups. Group C had similar osteogenetic quality of femoral head necrosis and angiogenesis with group D.@*CONCLUSION@#The treatment of rhBMP-2/PLGA implantation after core depression can promote the repair of rabbit femoral head necrosis. It is a promising and efficient synthetic bone material to treat the femoral head necrosis.

O uso de rhBMP-2/beta-TCP para técnica de enxerto vertical interposicional: relato de caso com quatro anos de acompanhamento / The use of rhBMP-2/beta-TCP for interpositional vertical graft technique: a case report with 4 years of follow-up

A reconstrução óssea de mandíbulas atróficas para o posicionamento de implantes dentários ainda é um grande desafio na Implantodontia atual. Para um ganho ósseo vertical, a técnica de enxerto interposicional com a utilização de enxerto de osso autógeno, ou algum substituto ósseo, apresentou excelentes resultados. Neste relato de caso, um paciente com 58 anos de idade e ausências entre os elementos 34 e 38 apresentava 3 mm de altura entre a crista óssea e o nervo alveolar inferior pelo exame de TCFC, impossibilitando o posicionamento de implantes sem enxertos prévios para ganho em altura e espessura. Com a utilização de rhBMP-2 como osteoindutor, associada ao beta-TCP como osteocondutor, foi possível regenerar o local com pouca morbidade e com ganho ósseo satisfatório (8 mm) para o posicionamento dos implantes. Após sete meses da consolidação do enxerto, implantes de diâmetro estreito (3,3 mm) foram posicionados e o paciente foi reabilitado sem complicações ou intercorrências durante todo o tratamento. Os autores sugerem que essa técnica tem um grande potencial para reconstruções de regiões atróficas, com um excelente ganho ósseo vertical, pouca morbidade e grande previsibilidade de resultados.

Bone reconstruction of atrophic mandibles for correct implant positioning is a great challenge on contemporary dentistry. Also, the interpositional graft technique using autogenous or bone substitute materials for vertical augmentation has presented excellent outcomes. This case report presents a 58 years-old patient with tooth loss from 34 to 38 regions having 3 mm from the bone crest to the inferior alveolar nerve canal according to the CBCT exam preventing implant placement without previous grafts for horizontal and vertical augmentation. With the aid of rhBMP-2 (osteoinductive) and beta-TCP (osteoconductive) materials it was possible to regenerate the area with less morbidity and satisfactory bone gain (8 mm) for implant placement. Seven months after graft healing narrow diameter implants (3.3 mm) were positioned and the patient rehabilitated without complications during the course of treatment. The authors suggest that this technique has a great potential for reconstruction of atrophic sites with excellent vertical bone gain, less morbidity, and great outcome predictability.

Aumento ósseo alveolar vertical e horizontal combinando osso autógeno, osso mineral particulado anorgânico homógeno, rhBMP-2/ACS e tela de titânio pós-exodontia na região mandibular anterior para colocação de implantes: relato de caso clínico com achados histológicos / Horizontal and vertical ridge augmentation combining autogenous-, mineral, particulate inorganic homogenous bone, rhBMP-2/ACS, and titanium mesh after tooth extraction in the anterior mandible for further dental implant placement: a clinical report with histological findings

Este relato de caso clínico descreve o uso da rhBMP-2/ACS para reconstrução de defeitos ósseos na região mandibular anterior. Paciente do sexo feminino, 63 anos de idade, mostrava esplintagem dos elementos 31 e 41 com resina composta e sinais de periodontite. Uma perda óssea alveolar extensa em forma de sela (15 mm de altura x 10 mm de largura) foi detectada nos exames radiográficos 2D e 3D (TCFC). O plano de tratamento incluiu: extração dentária, colocação de osso autógeno mentoniano, osso mineral anorgânico homógeno, rhBMP-2/ACS e tela de titânio, na mesma sessão. Após seis meses, uma nova cirurgia foi realizada para colocação de dois implantes de titânio (torque fi nal de inserção 35 Ncm), que foram deixados submersos. Uma biopsia, 12 meses após o enxerto, foi realizada e os resultados histológicos mostraram tecido ósseo viável sem sinais inflamatórios. A única intercorrência pós-operatória foi o edema esperado (dez dias). Duas coroas metalocerâmicas individuais foram confeccionadas sobre os cilindros calcináveis e entregues ao paciente. Dentro dos limites do caso e da extensão do defeito, resultados clínicos excelentes foram obtidos pela combinação dos biomateriais e dos implantes osseointegrados

This case report describes the use of rhBMP-2/ACS to reconstruct anterior mandibular bone defects. A 63 years-old female patient presented with a composite resin splinting at teeth 31 and 41 showing signs of periodontitis. A saddle-like extensive bone loss (15 mm in height x 10 mm in length) was detected on 2-D and 3-D (CBCT) image examination. The treatment planning included tooth extraction, chin bone graft, annorganic mineral graft, rhBMP-2/ACS, and a titanium mesh in the same clinical procedure. Six months later, the site was opened for dental implant placement (final insertion torque: 35 Ncm) and submersed healing. A biopsy was taken after 12 months and the histological results demonstrated viable bone tissue with no signs of inflammation. However, as expected, postoperative complications included edema in the grafted region. Finally, two metalloceramic restorations over burnout prosthetic cylinders were delivered to the patient. Within the limits of the bone defect, excellent clinical outcomes were observed by combining different biomaterials and osseointegrated implants.

Effect of recombinant human bone morphogenetic protein 2/poly-lactide-co-glycolic acid (rhBMP-2/PLGA) with core decompression on repair of rabbit femoral head necrosis

Objective: To observe the effect of recombinant human bone morphogenetic protein 2/poly-lactide-co-glycolic acid (rhBMP-2/PLGA) with core decompression on repair of rabbit femoral head necrosis. Method: Bilateral femoral head necrosis models of rabbit were established by steroid injection. A total of 48 rabbits (96 femoral head necrosis) were randomly divided into 4 groups: Group A, control group with12 rabbits, 24 femoral head necrosis; Group B, treated with rhBMP-2/PLGA implantation after core depression, with 12 rabbits, 24 femoral head necrosis; Group C, treated with rhBMP-2 implantation after core depression, with 12 rabbits, 24 femoral head necrosis; Group D treated with core depression group without implantation, with 12 rabbits, 24 femoral head necrosis. All animals were sacrificed after 12 weeks. The ability of repairing bone defect was evaluated by X-ray radiograph. Bone mineral density analysis of the defect regions were used to evaluate the level of ossification. The morphologic change and bone formation was assessed by HE staining. The angiogenesis was evaluated by VEGF immunohistochemistry. Results: The osteogenetic ability and quality of femoral head necrosis in group B were better than those of other groups after 12 weeks by X-ray radiograph and morphologic investigation. And the angiogenesis in group B was better than other groups. Group C had similar osteogenetic quality of femoral head necrosis and angiogenesis with group D. Conclusion: The treatment of rhBMP-2/PLGA implantation after core depression can promote the repair of rabbit femoral head necrosis. It is a promising and efficient synthetic bone material to treat the femoral head necrosis.