transforming-growth-factor-beta and Mandibular-Diseases

This study was an initial evaluation of the use of a bovine-derived bone protein (BP) extract that contains various growth factors combined with decalcified freeze-dried bone allograft (DFDBA) as regenerative treatment for class II mandibular furcations. Twenty-five patients were divided into 5 groups according to the dosage of BP present per mg of DFDBA to be grafted: (1) 0.00 microgram/mg, (2) 3.13 micrograms/mg, (3) 6.25 micrograms/mg, (4) 12.5 micrograms/mg, and (5) 25.0 micrograms/mg. Surgical exploration of the furcation defects was performed followed by grafting with BP/DFDBA. Results at 6 months showed that attachment gain in the treated furcation areas was greatest in Groups 4 and 5, suggesting that BP has the potential to increase the effects of DFDBA in gaining clinical attachment in mandibular class II furcations.

Topics: Adult; Aged; Animals; Bone Morphogenetic Proteins; Bone Regeneration; Bone Transplantation; Cattle; Dental Plaque Index; Double-Blind Method; Female; Follow-Up Studies; Furcation Defects; Gingival Recession; Humans; Male; Mandibular Diseases; Middle Aged; Observer Variation; Periodontal Attachment Loss; Periodontal Index; Periodontal Pocket; Prospective Studies; Reproducibility of Results; Statistics as Topic; Surgical Flaps; Transforming Growth Factor beta; Transplantation, Homologous

To describe a surgical technique using a regenerative approach and internal fixation for immediate reconstruction of critical size bone defects after segmental mandibulectomy in dogs.. Prospective case series.. Dogs (n = 4) that had reconstruction after segmental mandibulectomy for treatment of malignant or benign tumors.. Using a combination of extraoral and intraoral approaches, a locking titanium plate was contoured to match the native mandible. After segmental mandibulectomy, the plate was secured and a compression resistant matrix (CRM) infused with rhBMP-2, implanted in the defect. The implant was then covered with a soft tissue envelope followed by intraoral and extraoral closure.. All dogs that had mandibular reconstruction healed with intact gingival covering over the mandibular defect and had immediate return to normal function and occlusion. Mineralized tissue formation was observed clinically within 2 weeks and solid cortical bone formation within 3 months. CT findings at 3 months showed that the newly regenerated mandibular bone had ∼50% of the bone density and porosity compared to the contralateral side. No significant complications occurred.. Mandibular reconstruction using internal fixation and CRM infused with rhBMP-2 is an excellent solution for immediate reconstruction of segmental mandibulectomy defects in dogs.

Topics: Animals; Bone Morphogenetic Protein 2; Bone Plates; Bone Regeneration; Bone Substitutes; Dog Diseases; Dogs; Humans; Mandible; Mandibular Diseases; Mandibular Osteotomy; Mandibular Reconstruction; Plastic Surgery Procedures; Prospective Studies; Recombinant Proteins; Transforming Growth Factor beta

To test the hypothesis that a synthetic hydroxyapatite/β-tricalcium phosphate (HA/TCP) construct combined with polyethylene glycol (PEG) hydrogel including recombinant human bone morphogenetic proteins-2 (rhBMP-2) enhances new bone formation compared with bone morphogenetic proteins-2 (BMP-2) delivered using the HA/TCP construct alone.. Bilateral mandibular partial thickness 20 × 8 × 8 mm (L × W × H) alveolar defects were surgically created in the edentulated posterior mandible in 18 female minipigs. Randomized into two groups of nine animals each, the alveolar defects either received HA/TCP or HA/TCP/PEG with or without BMP-2 (105 μg/defect) in contra-lateral sites using a split-mouth design. Primary outcome, bone density (%) within four regions of interest, was evaluated following a 4-week healing interval when the animals were killed for histometric analysis.. Bone morphogenetic proteins-2 loaded onto HA/TCP constructs significantly enhanced new bone formation compared with HA/TCP controls. Adding PEG apparently obstructed BMP-2 induced bone formation.. Polyethylene glycol compromises the osteogenic effect of BMP-2.

Topics: Alveolar Bone Loss; Alveolar Process; Animals; Biocompatible Materials; Bone Density; Bone Morphogenetic Protein 2; Bone Substitutes; Calcium Phosphates; Drug Carriers; Female; Hydrogel, Polyethylene Glycol Dimethacrylate; Jaw, Edentulous, Partially; Mandible; Mandibular Diseases; Mandibular Reconstruction; Osteogenesis; Random Allocation; Recombinant Proteins; Swine; Swine, Miniature; Transforming Growth Factor beta

The purpose of these two pilot studies using animal bony defect models was to evaluate the influence of bone morphogenetic protein (BMP) and proportion of hydroxyapatite (HA)/beta-tricalcium phosphate (β-TCP) in biphasic calcium phosphate (BCP) graft on new bone formation.. In this study, four kinds of synthetic osteoconductive bone materials known for bone growth scaffold, OSTEON™II(HA:β-TCP 30:70), OSTEON™III (HA:β-TCP 20:80), OSTEON™II Collagen, and OSTEON™III Collagen, were prepared as BCP graft materials. In pilot study 1, three BCP materials (OSTEON™II, OSTEON™III, and OSTEON™II Collagen) were grafted in rabbit calvarial defects after impregnating in rhBMP-2. OSTEON™II without the rhBMP-2 impregnation was included in the study as the control. The amount of new bone was examined and measured histologically at 2, 4, and 8 weeks. In pilot study 2, four BCP materials (OSTEON™II, OSTEON™III, OSTEON™II Collagen, and OSTEON™III Collagen) were grafted in beagle dog mandibular defects after soaking in the rhBMP-2. The amount of total bone and new bone were measured three-dimensionally using microCT and healing process was examined histologically at 2, 4, and 8 weeks.. In pilot study 1, rhBMP-2 impregnated groups showed more new bone formation than the rhBMP-2 free group. In pilot study 2, increased new bone formation was observed in time-dependent manner after graft of BCP and BCP-collagen (OSTEON™II, OSTEON™III, OSTEON™II Collagen, and OSTEON™III Collagen) impregnated with rhBMP-2. Also, BCP with a higher proportion of HA (30% HA) showed more favorable result in new bone formation and space maintenance, especially at the 8 weeks.. From the results of the pilot studies, rhBMP-2 played positive roles in new bone formation and BCP could become a scaffold candidate for rhBMP-2 impregnation to induce new bone formation. Moreover, BCP with a higher proportion of HA (30% HA) could be considered more appropriate for rhBMP-2 carrier.

Topics: Animals; Bone Diseases; Bone Morphogenetic Protein 2; Bone Substitutes; Collagen Type I; Disease Models, Animal; Dogs; Hydroxyapatites; Imaging, Three-Dimensional; Mandible; Mandibular Diseases; Osteogenesis; Pilot Projects; Porosity; Rabbits; Recombinant Proteins; Skull; Time Factors; Tissue Scaffolds; Tooth Socket; Transforming Growth Factor beta; X-Ray Microtomography

This report describes the effect of periosteal-derived cells transfected with adenovirus-mediated bone morphogenetic protein-2 (BMP-2) on the repair of mandibular defects in rabbits.. Periosteal-derived cells were transfected with a replication-defective adenoviral vector encoding BMP-2, and the expression of BMP-2 was examined in transfected cells using in situ hybridization and enzyme-linked immunosorbent assay. In addition, the proliferation ability and activity of alkaline phosphatase of transfected cells were examined using the 3-[4,5-dimethylthiazol-2-Yl]-2,5-diphenyltetrazolium bromide method and enzymology, respectively. In vitro critical-size defects (about 10 × 6 mm) were made bilaterally in each rabbit mandible, and individual sites were implanted with tissue-engineered bone modified with an adenovirus construct encoding the recombinant human BMP-2 gene (Ad-BMP-2), tissue-engineered bone without modification, single bioactive glass ceramic, or no implants (control). New bone formation was evaluated by histochemical stain.. BMP-2 expression in the supernate of infected cells was detected from the first day after Ad-BMP-2 transfection and remained at a high level for at least 2 weeks. Alkaline phosphatase expression in transfected cells was significantly greater than in uninfected cells. The group of Ad-BMP-2-modified periosteal-derived cells formed more new bone than the other group at any time point.. Gene-modified tissue-engineered bone grafts have greater osteogenic potential than single tissue-engineered bone and single bioactive glass ceramic graft. Ex vivo Ad-BMP-2 transfer to periosteal-derived cells can increase bone formation in critical-size bone defects. Further studies are needed to determine if modified engineered cells can be developed for safe and effective clinical applications.

Topics: Adenoviridae; Alkaline Phosphatase; Animals; Bone Morphogenetic Protein 2; Bone Regeneration; Bone Substitutes; Cell Culture Techniques; Cell Proliferation; Cell Transplantation; Ceramics; Coloring Agents; Enzyme-Linked Immunosorbent Assay; Genetic Vectors; Guided Tissue Regeneration; Humans; In Situ Hybridization; Mandibular Diseases; Osteogenesis; Periosteum; Rabbits; Recombinant Proteins; Tetrazolium Salts; Thiazoles; Tissue Engineering; Tissue Scaffolds; Transfection; Transforming Growth Factor beta; Transplantation, Homologous

Microvascular osseous free tissue transfer is the standard of care for reconstructing significant mandibulectomy defects; however, this procedure can carry a significant rate of morbidity.. To describe the use of recombinant human bone morphogenetic protein 2 (rhBMP-2) as an option for segmental or near-complete rim mandibulectomy defects in a select group of patients, precluding the need for free tissue transfer.. A retrospective review was performed of 6 patients who had undergone repair of a mandible defect using rhBMP-2 with beta-tricalcium phosphate matrix or a cadaveric bone graft at a single tertiary care institution. The defects resulted from resection of benign neoplasms or from previous trauma. Reconstruction success was defined as no hardware problems, healing without infection, no need for further surgical procedures, and imaging evidence of healing and union without resorption. The median follow-up period was 37.5 months (range, 12-51 months).. Five of 6 patients underwent successful restoration of the mandibulectomy defect. One patient with a compromised immune system developed a significant postoperative wound infection requiring further reconstructive surgery.. The use of an rhBMP-2-based reconstructive approach is a feasible option for segmental or near-complete rim mandibulectomy defects in a select group of patients.. 4.

Topics: Ameloblastoma; Biocompatible Materials; Bone Morphogenetic Protein 2; Bone Transplantation; Calcium Phosphates; Female; Follow-Up Studies; Granuloma, Giant Cell; Guided Tissue Regeneration; Humans; Male; Mandibular Diseases; Mandibular Injuries; Mandibular Neoplasms; Mandibular Osteotomy; Mandibular Reconstruction; Middle Aged; Odontogenic Cysts; Recombinant Proteins; Reoperation; Retrospective Studies; Tissue Scaffolds; Transforming Growth Factor beta; Treatment Outcome

Osteoradionecrosis of the mandible is a debilitating consequence of radiation therapy for head-and-neck malignancy. It can result in pain, bone exposure, fistula formation, and pathologic fracture. Recombinant human bone morphogenetic protein 2 (rhBMP-2) has shown promise in reconstruction of bone defects. The purpose of this study is to determine whether the addition of rhBMP-2 at the union of vascularized bone and native bone improves surgical outcomes in patients with osteonecrosis of the mandible.. This study was a retrospective analysis of patients who were treated between 2006 and 2010 for osteonecrosis of the mandible. Patients requiring definitive reconstruction after failure of a course of conservative management were included. Patients were divided into 2 cohorts depending on whether rhBMP-2 was used during the reconstruction. The primary outcome measure was defined as stable mandibular union.. Seventeen patients were included. The development of malunion was similar in both groups (13% for rhBMP-2 group vs 11% for non-rhBMP-2 group). Infectious complications were similar between the groups (25% in rhBMP-2 group vs 56% in non-rhBMP-2 group, P = .33). The rates of hardware removal were similar for the 2 groups (33% in non-rhBMP-2 group vs 25% in rhBMP-2 group, P = .10). No cancer recurrences were observed in patients receiving rhBMP-2.. The use of rhBMP-2 is safe in free flap reconstruction of the mandible, but its ability to significantly improve patient outcomes, as measured by rates of malunion, reoperation, or infection, is still unknown.

Topics: Bone Morphogenetic Protein 2; Bone Plates; Bone Transplantation; Carcinoma, Squamous Cell; Cohort Studies; Device Removal; Female; Follow-Up Studies; Free Tissue Flaps; Head and Neck Neoplasms; Humans; Male; Mandible; Mandibular Diseases; Middle Aged; Osteoradionecrosis; Osteotomy; Plastic Surgery Procedures; Postoperative Complications; Recombinant Proteins; Retrospective Studies; Skin Transplantation; Surgical Wound Dehiscence; Surgical Wound Infection; Transforming Growth Factor beta; Treatment Outcome; Wound Healing

Implants coated with recombinant human bone morphogenetic protein-2 (rhBMP-2) induce relevant bone formation but also resident bone remodelling.. To compare the effect of implants fully or partially coated with rhBMP-2 on new bone formation and resident bone remodelling.. 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 mug rhBMP-2/implant. All implants were air-dried. The animals were euthanized at 8 weeks for histometric evaluation.. 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 mm(2) 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).. 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.

Topics: Alveolar Bone Loss; Animals; Bone Density; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Remodeling; Coated Materials, Biocompatible; Dental Implants; Dental Materials; Dental Prosthesis Design; Dogs; Fluorescent Dyes; Humans; Male; Mandibular Diseases; Microscopy, Electron, Scanning; Osseointegration; Osteogenesis; Oxytetracycline; Porosity; Postoperative Complications; Recombinant Proteins; Seroma; Surface Properties; Titanium; Transforming Growth Factor beta; Wound Healing

Endosseous implants coated with recombinant human bone morphogenetic protein-2 (rhBMP-2) in a laboratory bench setting and air-dried induce relevant bone formation but also resident bone remodeling. Thus, the objective of this study is to evaluate the effect of implants fully or partially coated with rhBMP-2 and vacuum-dried using an industrial process on local bone formation and resident bone remodeling.. 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 a rhBMP-2 solution (soak-load, six animals) for a total of 30 μg rhBMP-2 per implant. All implants were vacuum-dried. The animals were sacrificed at 8 weeks for histometric evaluation.. Clinical healing was unremarkable. Bone formation was not significantly affected by the rhBMP-2 application protocol. New bone height and area averaged (± SE) 3.2 ± 0.5 versus 3.6 ± 0.3 mm, and 2.3 ± 0.5 versus 2.6 ± 0.8 mm(2) for coronal-load and soak-load implants, respectively (P >0.05). The corresponding bone density and bone-implant contact registrations averaged 46.7% ± 5.8% versus 31.6% ± 4.4%, and 28% ± 5.6% versus 36.9% ± 3.4% (P >0.05). In contrast, resident bone remodeling was significantly influenced by the rhBMP-2 application protocol. Peri-implant bone density averaged 72.2% ± 2.1% for coronal-load versus 60.6% ± 4.7% for soak-load implants (P <0.05); the corresponding bone-implant contact averaged 70.7% ± 6.1% versus 47.2% ± 6.0% (P <0.05).. Local application of rhBMP-2 and vacuum-drying using industrial process seems to be a viable technology to manufacture implants that support local bone formation and osseointegration. Coronal-load implants obviate resident bone remodeling without compromising local bone formation.

Topics: Alveolar Bone Loss; Alveolar Process; Animals; Bone Density; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Remodeling; Coated Materials, Biocompatible; Dental Implantation, Endosseous; Dental Implants; Dental Prosthesis Design; Desiccation; Dogs; Humans; Immersion; Male; Mandible; Mandibular Diseases; Osseointegration; Osteogenesis; Radiography; Recombinant Proteins; Surface Properties; Titanium; Tooth Socket; Transforming Growth Factor beta; Vacuum

The use of recombinant bone morphogenetic protein-2 (rhBMP-2) with a collagen carrier material has severe limitations in regards to space maintenance. The aim of this study was to test whether rhBMP-2 combinations with allografts or a mesh enhance the regeneration of missing bone and the subsequent placement of dental implants.. In five dogs, surgically created ridge defects were augmented using one of the following treatment modalities: 1) rhBMP-2/absorbable collagen sponge (ACS) under a titanium mesh (Mesh); 2) rhBMP-2/ACS plus canine freeze-dried bone allograft; 3) rhBMP-2/ACS plus canine demineralized freeze-dried bone allograft (DFDBA); or 4) rhBMP-2/ACS wrapped around a canine cancellous allograft block (Block Allograft). Eight weeks later, dental implants were placed in the augmented areas. The dogs were sacrificed 16 weeks after bone augmentation and specimens obtained for histologic and histomorphometric analyses.. All sites augmented with DFDBA, and one site with Block Allograft did not allow placement of dental implants. In all other sites, dental implants were placed. The area of regenerated bone ranged between 23.40 mm(2) (freeze-dried bone allograft) and 35.16 mm(2) (Block Allograft). The greatest amount of bone was regenerated in the Block Allograft group ranging from 4.54 mm (at 1.5 mm), to 4.95 mm (at 3 mm), to 5.14 mm (at 4.5 mm). The least amount of bone was regenerated by the DFDBA group with values of 2.24 mm (at 1.5 mm), 2.84 mm (at 3 mm), and 3.34 mm (at 4.5 mm). Statistically significant differences were observed between DFDBA and block allograft at all three levels (P <0.001).. The combination of rhBMP-2 and a block allograft provides the greatest ridge width of the four treatment options used in this canine ridge augmentation model.

Topics: Absorbable Implants; Alveolar Process; Alveolar Ridge Augmentation; Animals; Bone Demineralization Technique; Bone Density; Bone Marrow; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Regeneration; Bone Remodeling; Bone Transplantation; Collagen; Dental Implantation, Endosseous; Dental Implants; Dogs; Freeze Drying; Male; Mandible; Mandibular Diseases; Random Allocation; Recombinant Proteins; Surgical Flaps; Surgical Mesh; Time Factors; Tissue Preservation; Titanium; Transforming Growth Factor beta; Transplantation, Homologous

Topics: Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Transplantation; Collagen; Drug Carriers; Humans; Mandibular Diseases; Plastic Surgery Procedures; Recombinant Proteins; Surgical Mesh; Titanium; Transforming Growth Factor beta; Treatment Outcome

New approaches to enhance vertical bone regeneration in clinically relevant implant models are needed. Therefore, we analyzed the impact of recombinant human bone morphogenic protein 2 (rhBMP-2) on the healing of large buccal alveolar defects during osseointegration of transgingivally inserted implants.. Twenty-four dental implants were inserted transgingivally in the mandibles of 6 labrador/golden retriever cross-bred dogs. Before implantation, a standardized buccal bone defect was created and refilled with either calcium phosphate as a carrier containing rhBMP-2 or calcium phosphate alone. Either ceramic abutments that enabled immediate implant loading or healing distance collars to prevent loading were mounted. Sixteen weeks after intervention, bone implant units were analyzed by radiofrequency analysis and histomorphometry.. In total, 14 implants (58.3%) were available for further analysis. The mean depth of the bone defects, the gain of regenerated bone, the vertical osseointegration of the implants, and the bone-to-implant contact in the newly formed bone were slightly greater in the rhBMP-2-containing samples. In contrast, the osseointegration in the preexisting bone was even superior within the non-rhBMP-2-treated specimen. However no differences were statistically significant.. When rhBMP-2-conducted bone regeneration was compared with control samples, no significant differences of newly formed bone were found at the bone-implant interface. The amounts of rhBMP-2 applied do not seem suitable to enhance implant osseointegration in large buccal defects.

Topics: Alveolar Bone Loss; Animals; Bone Matrix; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Regeneration; Calcium Phosphates; Ceramics; Dental Abutments; Dental Implants; Dental Materials; Dental Prosthesis Design; Dogs; Drug Carriers; Humans; Male; Mandible; Mandibular Diseases; Osseointegration; Osteoblasts; Osteogenesis; Recombinant Proteins; Surface Properties; Time Factors; Transforming Growth Factor beta

The off-label use of recombinant human bone morphogenetic protein-2 (rhBMP-2) for the treatment of mandibular bone defects was evaluated in 5 patients. The rhBMP-2 was used as an alternative to autogenous bone grafting.. A total of 5 patients had mandibular defects reconstructed with rhBMP-2, 1.5 mg/mL, soaked collagen sponges alone or in combination with bone marrow cells and allogenic cancellous bone chips. Four of the patients had mandibular continuity defects and the fifth patient had 2 large bone cavities following removal of dentigerous cysts. Radiographs and clinical examinations were used to evaluate healing. The longest patient follow-up was 22 months after reconstruction.. Radiographic and clinical assessments revealed bone regeneration and restoration of the mandibular defects in 3 of the 5 patients. The rhBMP-2 failed in 2 patients with continuity defects. Both patients with failed rhBMP-2 grafts were successfully repaired using autogenous harvested from the iliac crest.. Mandibular bone defects can be successfully reconstructed using rhBMP-2 soaked sponges with and without including bone marrow cells and allogenic bone. Further studies are needed to determine the ideal combination of components that will predictably and reliably regenerate bone in different types of bone defects.

Topics: Adult; Aged, 80 and over; Bone Marrow Transplantation; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Plates; Bone Regeneration; Bone Transplantation; Collagen; Female; Fractures, Comminuted; Humans; Jaw Cysts; Male; Mandible; Mandibular Diseases; Mandibular Fractures; Osteomyelitis; Recombinant Proteins; Tissue Engineering; Transforming Growth Factor beta

Several autogenous bone grafting techniques are available for the restoration of large continuity defects of the mandible. However, these procedures are associated with limitations involving postoperative morbidity, difficulty in ambulation, and pain. The development of a technique of surgical reconstruction not involving autogenous bone would offer new opportunities for facial bone reconstruction, particularly of the mandible. This study was instituted to observe the effect of rhBMP-2 in a collagen carrier without concomitant bone grafting material in the restoration of continuity critical-sized defects of the mandible.. A case review was made of 14 patients who were selected from a larger group having received BMP-2 in different categories of mandibular defects. The rhBMP-2 in all the cases reported here was used alone with the collagen carrier without concomitant bone materials. The cases involved lesions of the body and angle of the mandible in 2 categories: 1) defects resulting from neoplastic diseases, and 2) defects secondary to osteomyelitis (related to bisphosphonates or irradiation). A total dose of 4 to 8 mg of rhBMP-2 was delivered to the surgical site in concentrations of 1.5 mg per cc (depending on the size of lesion). Cases were followed over a period from 6 to 18 months. Occlusal function was restored with implant-borne or conventional prosthesis.. All of the cases reported here had successful osseous restoration of the edentulous area followed by prosthetic treatment. Bone formation in the surgical area could be palpated at the end of 3 to 4 months and identified radiographically at the end of 5 to 6 months. The maintenance of a periosteal envelope was effected by the use of a superiorly placed minibar in the upper portion of the defect, or with the use of titanium mesh superiorly. This metallic tenting up to the mucosa is thought to be necessary to maintain the space for osseous regeneration.. This study indicated that the use of rhBMP-2 without concomitant bone grafting materials in large critical sized mandibular defects produced excellent regeneration of the area establishing the basis for the return of prosthodontic function. This study tends to support the use of cytokines, particularly rhBMP-2, in osseous regeneration or repair of facial bones. The technique describes a new alternative to various types of autogenous bone grafting procedures for the treatment of critical sized bony lesions of the mandible.

Topics: Adolescent; Age Factors; Aged; Aged, 80 and over; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Regeneration; Collagen; Drug Carriers; Female; Humans; Jaw Fixation Techniques; Male; Mandible; Mandibular Diseases; Mandibular Neoplasms; Middle Aged; Oral Surgical Procedures; Osteomyelitis; Plastic Surgery Procedures; Recombinant Proteins; Surgical Sponges; Transforming Growth Factor beta

Traditional bone grafting relies upon the incorporation of a bone-cell bearing structure into a recipient site. The graft serves as a scaffold that is eventually replaced and remodeled. This process is known as osteoconduction. Recombinant human bone morphogenetic protein-2 (rhBMP-2) is commercially available as an acellular implant in which the protein is bound to an absorbable collagen sponge (ACS). The rhBMP-2/ACS implant converts undifferentiated mesenchymal stem cells into osteoblasts and promotes an intense local neovascular response. This process, known as osteoinduction, produces bone via membranous, chondroid, or endochondral ossification. The type of bone synthesis depends upon the mesenchymal substrate and the local cellular environment. Using this simple technique, bone defects can be resynthesized with good outcomes and a significant reduction in donor site morbidity. Repair of a critical-sized mandibular resection defect with ISO is described. Basic science concepts of rhBMP-2, relevant histopathologic findings, and clinical application are described.

Topics: Animals; Biocompatible Materials; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Regeneration; Bone Remodeling; Cell Differentiation; Cell Proliferation; Collagen; Disease Models, Animal; Gelatin Sponge, Absorbable; Humans; Mandible; Mandibular Diseases; Mesenchymal Stem Cells; Osteoblasts; Osteocytes; Osteogenesis; Osteogenesis, Distraction; Recombinant Proteins; Swine; Transforming Growth Factor beta

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.. 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.. 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.. The bioglass and demineralized/mineralized bone matrix biomaterials utilized in this study in combination with rhBMP-2/ACS supported clinical and histological ridge augmentation.

Topics: Alveolar Bone Loss; Alveolar Process; Alveolar Ridge Augmentation; Animals; Biocompatible Materials; Bone Matrix; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Regeneration; Bone Substitutes; Ceramics; Dogs; Drug Carriers; Drug Delivery Systems; Fluorescent Dyes; Gelatin Sponge, Absorbable; Humans; Male; Mandibular Diseases; Osteogenesis; Recombinant Proteins; Transforming Growth Factor beta

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

Topics: Analysis of Variance; Animals; Bite Force; Bone Density; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Regeneration; Bone Remodeling; Dental Implantation, Endosseous; Dental Implants; Dental Occlusion; Dental Prosthesis, Implant-Supported; Denture, Partial; Dogs; Drug Carriers; Gelatin Sponge, Absorbable; Humans; Lactic Acid; Male; Mandible; Mandibular Diseases; Osseointegration; Osteogenesis; Osteotomy; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Recombinant Proteins; Time Factors; Transforming Growth Factor beta

Alveolar bone resorption and atrophy of the mandible are a major challenge for regeneration medicine. In the present investigation, a collagen sponge that contained TGF-beta1 was placed at a mandibular defect and the osteogenic effects of collagen-TGF-beta1, complex were evaluated.. The Pm2, Pm3, and Pm4 teeth on both sides of the mandibles of 12 adult beagle dogs (9.0-12.0 kg) were extracted. After the extraction-site wounds healed, a bone defect (10.0 x 15.0 mm-wide, 10.0 mm-deep or 10.0 x 10.0 mm-wide, 10.0 mm-deep) was created on the mandible. A collagen sponge (10.0 x 10.0 x 10.0 mm) that contained TGF-beta1 (1.0 microg, 5.0 microg, or 10.0 microg, in physiological saline) was placed at the bottom of the defect and the overlying mucous membrane was sutured with 4-0 prolene. As a control, a collagen sponge that contained physiological saline only was placed in a defect on the opposite side. Two weeks after the surgery the wounds above the bone defects on both the control and TGF-beta1-treated sides had healed completely.. At four, six, or eight weeks post-operatively animals were killed. Soft X-ray and bone-salt measurement analyses confirmed clearly that there was greater calcified bone formation in the defects into which TGF-beta1 had been incorporated than with the control defects. The implanted collagen sponges were fully resorbed and the bone tissue had regenerated from the bottom of the defects on the TGF-beta1, side by four weeks. On the control side, no such regeneration was observed.. These results indicate that TGF-beta1, released slowly from a collagen sponge was effective in promoting bone remodeling when applied to mandibular defects in adult dogs.

Topics: Alveolar Bone Loss; Animals; Bone Regeneration; Collagen; Disease Models, Animal; Dogs; Drug Carriers; Guided Tissue Regeneration, Periodontal; Mandibular Diseases; Plastic Surgery Procedures; Random Allocation; Sensitivity and Specificity; Transforming Growth Factor beta; Transforming Growth Factor beta1; Treatment Outcome; Wound Healing

Bone morphogenetic proteins (BMPs) are capable of inducing endochondral bone formation when applied on biologic carriers in numerous mammalian in vivo assay systems. Bone morphogenetic protein gene therapy is also currently being developed to promote osteogenesis for clinical indications such as spinal fusions, craniofacial bone loss, and osteoporosis. In this study, critical-sized mandibular defects were treated with a control adenoviral vector (Ad-beta-gal), a BMP-2 adenoviral vector (Ad-BMP-2), or a BMP-9 adenoviral vector (Ad-BMP-9). Gross tissue examination, radiographic analysis, and histologic analysis demonstrated significant bony healing in the BMP treated groups compared to controls. Osteogenesis was limited to the bony defect, without extension into the surrounding soft tissues. The study suggests that with further development, BMP gene therapy may be potentially useful for repair of bony defects in the craniofacial region.

Topics: Animals; beta-Galactosidase; Bone Marrow; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Regeneration; Cytomegalovirus; Follow-Up Studies; Genetic Therapy; Genetic Vectors; Growth Differentiation Factor 2; Image Processing, Computer-Assisted; Mandible; Mandibular Diseases; Osteogenesis; Osteoporosis; Rats; Rats, Nude; Spinal Fusion; Tomography, X-Ray Computed; Transforming Growth Factor beta; Wound Healing

Bone defects and irregularities are major problems for dental implant and periodontal therapies.. 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.. 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).. 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.

Topics: Animals; Biocompatible Materials; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Regeneration; Coloring Agents; Drug Carriers; Eosine Yellowish-(YS); Fluorescent Dyes; Gelatin; Hematoxylin; Humans; Lactic Acid; Male; Mandible; Mandibular Diseases; Osteogenesis; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Rats; Rats, Long-Evans; Recombinant Proteins; Transforming Growth Factor beta

Insufficient or absence of bone healing is a frequent problem within all surgical fields. This often necessitates treatment by autogenous bone grafting. Recently, two new techniques to promote bone healing were introduced, the osteopromotive membrane technique, and local delivery of growth-stimulatory factors, both with a high rate of success in preclinical experiments. The aims of the present series of investigations were to further develop the membrane barrier technique, both by itself as well as in combination with local delivery of growth factors, in animal experiments. During membrane-promoted bone formation, the membrane porosity was found to be of importance for the initial rate of bone formation as well as for the performance of the material in the tissue. In contrast, the final amount of bone was not affected. In a well-known bone healing model, the 5 mm in diameter 'critical size defect' at the rat mandibular ramus, the efficacy of rhBMP-2, rhTGF-beta 1 and rhFGF-2 to promote bone regeneration alone and in combination with barrier membranes was evaluated. Under both conditions, rhBMP-2 was found to be an efficient promoter of bone healing. rhFGF-2 had some stimulatory effect both with and without barrier membranes, whereas rhTGF-beta 1 was found to have a minor stimulatory effect by itself, but in combination with barrier membranes it was inhibitory. These observations were interpreted as being the result of an effect of the growth factors at different levels of the osteoblastic lineage; rhBMP-2 being an inducer of osteoblastic cells from stem cells, whereas rhTGF-beta 1 may primarily act on already committed cells. In contrast, rhFGF-2 may have stimulatory effect at different levels of the lineage. Based on the positive results obtained by the combination of rhBMP-2 and barrier membranes in the rat mandible, this combination was then applied to (i) rabbit radius defects; and (ii) a rat calvarial osteoneogenesis model. In the long bone model, membranes by themselves were insufficient to promote bone healing, but the combination resulted in complete regeneration. In the osteoneogenesis model, the combination of barrier membranes and rhBMP-2 resulted in a 100% increase in the final amount of achievable bone. In the last study, rhFGF-2 (no barrier membranes) was shown to enhance revitalization of autoclaved autogenous bone grafts, a procedure clinically used in craniofacial reconstruction mainly after tumor surgery. The combined use of rhBMP-2 and

Topics: Administration, Topical; Animals; Bone Diseases; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Regeneration; Bone Transplantation; Cell Lineage; Combined Modality Therapy; Disease Models, Animal; Equipment Design; Fibroblast Growth Factor 2; Male; Mandible; Mandibular Diseases; Membranes, Artificial; Osteoblasts; Osteogenesis; Porosity; Rabbits; Radius; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Skull; Skull Neoplasms; Stem Cells; Transforming Growth Factor beta; Transplantation, Autologous; Wound Healing

To determine the immunocytochemical pattern of expression of transforming growth factor (TGF) alpha, epidermal growth factor (EGF), and TGF beta in the three most common types of odontogenic jaw cyst.. Growth factor expression was detected in paraffin wax sections of odontogenic cysts (27 odontogenic keratocysts, 10 dentigerous cysts, and 10 radicular cysts) using a streptavidin-biotin peroxidase technique with monoclonal antibodies directed against TGF alpha (clone 213-4.4) and TGF beta (clone TB21) and a polyclonal antibody directed against EGF (Z-12).. The epithelial linings of all cysts showed reactivity for TGF alpha which was mainly localised to basal and suprabasal layers. Odontogenic keratocyst linings expressed higher levels of TGF alpha than those of dentigerous and radicular cysts, with 89% (24/27) of odontogenic keratocysts exhibiting a strong positive reaction compared with 50% (five of 10) of dentigerous and radicular cysts, respectively. EGF reactivity was similar in all cyst groups, weaker than that for TGF alpha and predominantly suprabasal. TGF alpha and EGF were also detected in endothelial cells, fibroblasts and inflammatory cells within the cyst walls. The most intense TGF beta staining in odontogenic cysts was extracellular within the fibrous tissue capsules, irrespective of cyst type.. These results, together with previous studies of EGF receptor, indicate differential expression of TGF alpha, EGF and their common receptor between the different types of odontogenic cyst, suggesting that these growth factors (via autocrine or paracrine, or both, pathways) may be involved in their pathogenesis.

Topics: Dentigerous Cyst; Epidermal Growth Factor; Growth Substances; Humans; Immunoenzyme Techniques; Mandibular Diseases; Maxillary Diseases; Odontogenic Cysts; Radicular Cyst; Transforming Growth Factor alpha; Transforming Growth Factor beta