transforming-growth-factor-beta and Mandibular-Neoplasms

Topics: Adult; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Regeneration; Bone Substitutes; Bone Transplantation; Humans; Male; Mandible; Mandibular Neoplasms; Recombinant Proteins; Transforming Growth Factor beta; Young Adult

Recombinant human morphogenetic protein (rhBMP) is a graft alternative for extensive mandibular reconstruction after tumor resections. However, the feasibility of rhBMP-2 to receive osseointegrated implants and prosthetic rehabilitation has been rarely reported. This study reports on a case of an extensive solid ameloblastoma along the mandibular body. The treatment consisted of resection followed by off-label use of rhBMP type 2 associated with bovine bone xenograft. Eleven months postoperatively, the patient was prosthetically rehabilitated with dental implants, without evidence of resorption or complications. The literature on mandibular reconstructions using rhBMP and their feasibility for future osseointegrated implant placement was also reviewed. Based on the presented case, the association between rhBMP-2 and a bovine bone xenograft could be considered a feasible option for the reconstruction and rehabilitation of large mandibular defects after tumor resection. According to the literature, the use of rhBMP as a graft material is encouraging, with good clinical outcome. However, there are no long-term studies demonstrating success and survival rates of implants placed in these grafts. Future investigations will be required to ascertain the long-term survival of implants in areas grafted with rhBMP. Also, there is a lack of information regarding the prosthetic rehabilitation of these patients.

Topics: Absorbable Implants; Adult; Ameloblastoma; Animals; Bone Morphogenetic Protein 2; Bone Transplantation; Cattle; Collagen; Dental Implantation, Endosseous; Dental Implants; Dental Prosthesis, Implant-Supported; Denture, Partial; Feasibility Studies; Follow-Up Studies; Heterografts; Humans; Male; Mandibular Neoplasms; Mandibular Reconstruction; Membranes, Artificial; Minerals; Osseointegration; Recombinant Proteins; Surgical Mesh; Transforming Growth Factor beta

Numerous autogenous bone-grafting procedures are available for the recovering of large continuity defects of the mandible. However, these surgical techniques present several limitations involving postoperative morbidity and pain. The development of new bone technique reconstruction not involving autogenous bone graft would offer new opportunities for facial bone reconstruction. This report highlights the possibility of recombinant human bone morphogenetic protein type 2 (rhBMP-2) application without concomitant bone grafting material in the restoration of continuity critical-sized defects after tumor resection in the mandible. The presented case shows a large mandibular reconstruction after tumor removal in a 31-year-old white man affected by ameloblastoma. In this case, the rhBMP-2 application with a carrier consisted on absorbable collagen sponge gives excellent newly formed bone at 18 months of control clinical and radiologic follow-up. The results indicated that the use of rhBMP-2 without concomitant autogenous bone grafting materials in large critical-sized mandibular defects secondary to large mandibular tumor produced excellent regeneration of the treated area.

Topics: Absorbable Implants; Adult; Allografts; Ameloblastoma; Bone Morphogenetic Protein 2; Bone Regeneration; Collagen; Drug Carriers; Follow-Up Studies; Humans; Male; Mandibular Neoplasms; Mandibular Reconstruction; Osteogenesis; Plastic Surgery Procedures; Recombinant Proteins; Surgical Mesh; Transforming Growth Factor beta

Large mandibular resection defects historically have been treated using autogenous bone grafts and reconstruction plates. However, a major drawback of large autogenous bone grafts is donor-site morbidity.. This report describes the replacement of a 10-cm anterior mandibular ameloblastoma resection defect, reproducing the original anatomy of the chin, using a tissue-engineered construct consisting of β-tricalcium phosphate (β-TCP) granules, recombinant human bone morphogenetic protein-2 (BMP-2), and Good Manufacturing Practice-level autologous adipose stem cells (ASCs). Unlike prior reports, 1-step in situ bone formation was used without the need for an ectopic bone-formation step. The reconstructed defect was rehabilitated with a dental implant-supported overdenture. An additive manufactured medical skull model was used preoperatively to guide the prebending of patient-specific hardware, including a reconstruction plate and titanium mesh. A subcutaneous adipose tissue sample was harvested from the anterior abdominal wall of the patient before resection and simultaneous reconstruction of the parasymphysis. ASCs were isolated and expanded ex vivo over the next 3 weeks. The cell surface marker expression profile of ASCs was similar to previously reported results and ASCs were analyzed for osteogenic differentiation potential in vitro. The expanded cells were seeded onto a scaffold consisting of β-TCP and BMP-2 and the cell viability was evaluated. The construct was implanted into the parasymphyseal defect.. Ten months after reconstruction, dental implants were inserted into the grafted site, allowing harvesting of bone cores. Histologic examination and in vitro analysis of cell viability and cell surface markers were performed and prosthodontic rehabilitation was completed.. ASCs in combination with β-TCP and BMP-2 offer a promising construct for the treatment of large, challenging mandibular defects without the need for ectopic bone formation and allowing rehabilitation with dental implants.

Topics: Adipose Tissue; Ameloblastoma; Bone Morphogenetic Protein 2; Bone Plates; Bone Regeneration; Bone Substitutes; Calcium Phosphates; Cell Culture Techniques; Cell Differentiation; Cell Survival; Dental Implants; Dental Prosthesis, Implant-Supported; Denture, Overlay; Denture, Partial; Follow-Up Studies; Humans; Male; Mandibular Neoplasms; Middle Aged; Neoplasm Recurrence, Local; Osseointegration; Osteogenesis; Plastic Surgery Procedures; Recombinant Proteins; Stem Cells; Subcutaneous Fat, Abdominal; Surgical Mesh; Tissue Engineering; Tissue Scaffolds; Transforming Growth Factor beta

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

The US Food and Drug Administration has approved recombinant human bone morphogenetic protein 2 (rhBMP-2) (Infuse Bone Graft; Medtronic Sofamor Danek, Minneapolis, MN) as an alternative to autogenous bone graft for sinus augmentations and for localized alveolar ridge augmentations for defects associated with extraction sockets. The objective of this analysis was to characterize adverse events reported after the use of rhBMP-2 in oral and maxillofacial procedures.. The US Food and Drug Administration's Manufacturer and User Facility Device Experience database contains reports of adverse events involving medical devices. The publicly available version of the database was searched for reports for the brand name Infuse Bone Graft. Descriptive statistics were used to summarize the procedures and adverse events.. As of April 30, 2011, the Manufacturer and User Facility Device Experience database contained 83 reports of adverse events after oral and maxillofacial operations involving rhBMP-2. Of these reports, 55 (66.3%) described off-label uses, such as reconstruction of the mandible after fracture or cancer or alveolar cleft repair. The most commonly reported adverse events included local reactions, graft failure, infections, and other wound complications. Of the reports, 25 (30.1%) stated that the patient required additional surgery to address the reported adverse event.. Serious adverse events, some of which may require a second operation, can occur after the use of rhBMP-2 in oral and maxillofacial procedures. In this analysis graft, failure and pseudarthrosis were more commonly reported after off-label uses of rhBMP-2 than approved uses.

Topics: Adverse Drug Reaction Reporting Systems; Alveolar Process; Bone Morphogenetic Protein 2; Cleft Palate; Databases as Topic; Drug Monitoring; Graft Survival; Humans; Mandibular Fractures; Mandibular Neoplasms; Off-Label Use; Oral Surgical Procedures; Plastic Surgery Procedures; Pseudarthrosis; Recombinant Proteins; Reoperation; Surgical Wound Infection; Transforming Growth Factor beta; United States; United States Food and Drug Administration

Ameloblastoma is a locally aggressive tumor most often found in posterior body and angle of the mandible. Although ameloblastoma has histological characteristics of benignity, they have a high percentage of local recurrence and possible malignant development if treated improperly.. This report presents a treatment of unusual mandibular sequelae after tumor resection using recombinant human bone morphogenetic protein-2 (rhBMP-2) associated with hydroxyapatite (HA) and calcium triphosphate (TCP).. Seven months after surgery, the patient was asymptomatic, with stable occlusion and class I, without signs of infection or rejection, and bone repair with rigidity compatible to an immature bone structure was observed. Reconstruction of large mandibular bone defect with a combination of rhBMP-2 and HA/TCP achieving a satisfactory result with less invasive and minimum morbidity has been demonstrated.

Topics: Adult; Ameloblastoma; Biocompatible Materials; Bone Morphogenetic Protein 2; Bone Plates; Bone Substitutes; Bone Transplantation; Calcium Phosphates; Collagen; Cutaneous Fistula; Device Removal; Drug Carriers; Durapatite; Equipment Failure; Female; Follow-Up Studies; Humans; Mandibular Neoplasms; Oral Fistula; Plastic Surgery Procedures; Recombinant Proteins; Surgical Mesh; Surgical Wound Dehiscence; Surgical Wound Infection; Transforming Growth Factor beta

The objective of this study was to investigate radiation-induced late changes in cutaneous gene expression using a microarray platform and quantitative, real-time, reverse-transcriptase polymerase chain reaction (RT-PCR) validation.. Paired irradiated and nonirradiated skin biopsies were obtained from 19 patients with a history of oral squamous cell carcinoma (OSCC) treated by surgery and adjuvant radiotherapy at the time of secondary corrective surgery. Topic-defined PIQOR (Parallel Identification and Quantification of RNAs) skin microarrays were used to compare gene expression profiles between control and irradiated skin sample in 8 patients. The data were validated for matrixmetalloproteinase (MMP)-1 and tissue-inhibitor of matrixmetalloproteinase (TIMP)-1 by RT-PCR for all patients.. Irradiation markedly enhanced the expression of molecules associated with the transforming growth factor (TGF)-beta(1) signaling pathway, blood vessel development, as well as extracellular matrix constitution and turn-over.. Our data suggest that radiation-induced late changes in cutaneous gene expression mainly affect molecules related to extracellular matrix (ECM)-constitution and-remodeling.

Topics: Aged; Aged, 80 and over; Biopsy; Bone Transplantation; Carcinoma, Squamous Cell; Extracellular Matrix; Female; Fibrosis; Gene Expression Regulation; Humans; Male; Mandibular Neoplasms; Matrix Metalloproteinase 1; Middle Aged; Neoadjuvant Therapy; Neovascularization, Physiologic; Oligonucleotide Array Sequence Analysis; Plastic Surgery Procedures; Radiation Injuries; Radiotherapy, Adjuvant; Radiotherapy, Intensity-Modulated; Reverse Transcriptase Polymerase Chain Reaction; Skin; Skin Transplantation; Tissue Inhibitor of Metalloproteinase-1; Transforming Growth Factor beta; Wound Healing

Giant cell tumor (GCT) is a relatively common skeletal tumor. Mandibular localization of this tumor is usually treated with resection of the tumor area. 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 (hip graft), 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 aims to underline the effect of recombinant human bone morphogenetic protein type 2 (rhBMP-2) in a collagen carrier with concomitant bone grafting material in the restoration of continuity critical-size defects after GCT resection in the mandible. The rhBMP-2 was used with absorbable collagen sponge. A total dose of 4 to 8 mg of rhBMP-2 was delivered to the surgical site in concentrations of 1.5 mg/mL. The patient was followed up over a period from 6 to 18 months. Occlusal function was initially restored with conventional prosthesis. 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 results clearly indicated that the use of rhBMP-2 without concomitant bone grafting materials in large critical-size mandibular defects secondary to GCT produced excellent regeneration of the area, establishing the basis for the return of prosthodontic function.

Topics: Adult; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Plates; Bone Regeneration; Bone Transplantation; Drug Carriers; Female; Follow-Up Studies; Gelatin Sponge, Absorbable; Giant Cell Tumor of Bone; Humans; Jaw Fixation Techniques; Mandible; Mandibular Neoplasms; Osteogenesis; Plastic Surgery Procedures; Pregnancy; Pregnancy Complications, Neoplastic; Recombinant Proteins; Transforming Growth Factor beta

The limitations and morbidity associated with autogenous bone grafting have driven the search for predictable bone substitutes and bioimplants. A novel method of reconstruction was tested in this case series.. Ten patients with major mandibular defects following resection of biopsy-proven ameloblastoma lesions or osteomyelitis of the mandibular body or ramus were included in this study. The resection defects were spanned with rigid reconstruction plates to hold the remaining mandibular segments in the correct position. The defects were filled with a bioimplant containing bone morphogenetic protein-7 (BMP-7) in a demineralized bone matrix (DBM) suspended in a reverse-phase medium to effect sustained BMP delivery.. The postoperative course for all 10 patients was uneventful. Radiographic evidence of mandibular bone formation was found in all cases. At the end of 1 year, functional and esthetic reconstruction of the mandible was complete.. Bioimplants containing BMP-7 in DBM suspended in a reverse phase medium were successful in restoring major mandibular defects in nonirradiated beds in this series of 10 patients.

Topics: Absorbable Implants; Adolescent; Adult; Aged; Ameloblastoma; Bone Matrix; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Bone Plates; Bone Regeneration; Bone Substitutes; Female; Humans; Male; Mandible; Mandibular Neoplasms; Middle Aged; Oral Surgical Procedures; Plastic Surgery Procedures; 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

Examples of defects including mandibular continuity defects, preprosthetic atrophic alveolar ridge deficiencies, traumatic defects, and maxillary clefts were included.. All patients demonstrated osseous regeneration stimulated by rhBMP-2.. rhBMP-2 is successful in regenerating bone in a variety of maxillofacial defects. In the future, rhBMP-2 will play a significant role in the treatment of bone deficiencies.

Topics: Adolescent; Alveolar Ridge Augmentation; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Regeneration; Bone Transplantation; Child; Cleft Palate; Female; Humans; Male; Mandibular Neoplasms; Maxilla; Maxillofacial Injuries; Middle Aged; Oral Surgical Procedures; Plastic Surgery Procedures; Recombinant Proteins; Transforming Growth Factor beta; Wounds, Gunshot

To report treatment of a complex odontoma of the mandible by partial mandibulectomy and immediate surgical reconstruction using bridging plate fixation with a synthetic graft.. Clinical case report.. A 4-year-old male castrated cocker spaniel.. Immediate reconstruction of the left mandible (5 cm gap) was performed after complete excision of a complex odontoma. Locking plate fixation was applied immediately before complete excision of the mass. Fixation was removed, then after partial mandibulectomy, including all abnormal tissue, restored to achieve occlusion. The resulting mandibular defect was filled with recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered in an absorbable collagen sponge containing hydroxyapatite/tricalcium phosphate granules (compression resistant matrix [CRM]).. New bone growth was evident radiographically and on palpation at 3 months. Bony remodeling was evident during follow-up examinations up to 26 months. Bone collected by biopsy at the graft site at 7 months had robust new bone formation and evidence of continued remodeling. Only minor complications (repeated intraoral plate exposure) were encountered postoperatively and were easily resolved.. An osteoinductive factor (rhBMP-2/CRM) was successfully used as a graft substitute in immediate reconstruction of a large mandibular defect.. Immediate reconstruction of large mandibular defects with osteoinductive materials as a graft substitute may be a viable alternative to partial mandibular resection or radiation therapy for benign odontogenic tumors in dogs.

Topics: Animals; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Plates; Dog Diseases; Dogs; Male; Mandible; Mandibular Neoplasms; Odontoma; Transforming Growth Factor beta; Treatment Outcome

Topics: Biocompatible Materials; Bone Density; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Bone Plates; Bone Regeneration; Bone Substitutes; Calcium Phosphates; Child, Preschool; Collagen; Durapatite; Fibroma, Ossifying; Follow-Up Studies; Humans; Male; Mandible; Mandibular Neoplasms; Neoplasm Recurrence, Local; Osteogenesis; Periosteum; Plastic Surgery Procedures; Recombinant Proteins; Stem Cells; Transforming Growth Factor beta

The purpose of this study was to analyze the mechanism of bone invasion in carcinoma of the mandibular gingiva. We investigated 38 specimens of lower gingival carcinoma and histopathologically classified them into an invasion group (23 cases) and a non-invasion group (15 cases) on the basis of light microscopy evidence. These specimens were examined using immunohistochemical techniques involving antibodies of parathyroid hormone-related protein (PTHrP), tumor necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, -1beta, -6, -11, -18 and transforming growth factor (TGF)-beta. The invasion group showed a high level of expression of PTHrP, TNF-alpha, IL-6 and IL-11 positive cells (P<0.01 versus non-invasion group). The difference in the levels of expression of IL-1alpha, -1beta, -18 and TGF-beta positive cells was not significant between these two groups. Our results suggest that various cancer-derived cytokines, such as PTHrP, TNF-alpha, IL-6 and IL-11, play an important role in the mechanism of bone invasion associated with lower gingival squamous cell carcinoma.

Topics: Aged; Bone Resorption; Carcinoma, Squamous Cell; Cytokines; Female; Gingival Neoplasms; Humans; Immunohistochemistry; Interleukins; Male; Mandibular Neoplasms; Middle Aged; Neoplasm Invasiveness; Osteoclasts; Parathyroid Hormone-Related Protein; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Dysregulation of TGF beta 2, a modulator of cell growth and differentiation, can result in uncontrolled growth and tumor formation. Our comparative studies on the expression of TGF beta 2 mRNA and protein indicate that TGF beta 2 may primarily be a regulator of epithelial differentiation during tooth development (between 13 and 20 gestational wk) and tumorigenesis of odontogenic neoplasms. A paracrine mode of action for TGF beta 2 in early human tooth germ (cap/early bell stage) is suggested by location of mRNA in the mesenchyme surrounding the tooth germ, whereas protein is found in the epithelial dental lamina and enamel organ. During the late bell stage, TGF beta 2 gene expression shifted from the mesenchyme to the odontogenic epithelium and was colocalized with protein, suggesting an autocrine role for the terminal differentiation of ameloblasts. In odontogenic tumors of epithelial origin (ameloblastomas) and epithelial-ectomesencymal origin (ameloblastic fibromas), TGF beta 2 mRNA was mostly located in the mesenchymal tumor component and protein in the epithelial tumor component. Odontogenic ectomesenchymal tumors (myxomas) were not associated with TGF beta 2 mRNA and protein expression. The results imply that TGF beta 2 may play an important role in epithelial-mesenchymal interactions in human tooth morphogenesis and development of odontogenic tumors.

Topics: Adolescent; Adult; Base Sequence; Cell Differentiation; Child, Preschool; Epithelial Cells; Female; Fetus; Gene Expression; Gestational Age; Humans; In Situ Hybridization; Male; Mandible; Mandibular Neoplasms; Maxillary Neoplasms; Molecular Sequence Data; Myxoma; Odontogenesis; Odontogenic Tumors; Oligodeoxyribonucleotides; Oligonucleotides, Antisense; Polymerase Chain Reaction; RNA, Messenger; Tooth Germ; Transforming Growth Factor beta