| Objective:Adequate bone is an important prerequisite for the success of implant-supported denture. However, edentulous alveolar bone loss often occurred in the clinical. It is unable to meet the needs of implant surgery. The emergence of various bone augmentation techniques can remedy this deficiency. Bone substitute material is bone augmentation techniques essential conditions to some extent. However, the artificial bone substitute materials cannot fully meet the clinical needs. In this study, recombinant human bone morphogenetic protein-2 (rhBMP-2) was combined with currently used artificial bone substitute material. New bone formation was analyzed ability to predict its clinical effects through cell culture, animal models and clinical trials. The present study includes three parts:Part one-The effect of rhBMP2 combined with artificial bone substitute materials on the proliferation and differentiation of osteoblasts; Part two-The study of bone repair effect of rhBMP2 combined with artificial bone substitute materials in alveolar defect around the dental implant- an animal study; and Part three:Clinical observation of rhBMP-2 incorporation on the bone defect repair capacity of Bio-oss.PART ONE- The effect of rhBMP2 combined with artificial bone substitute materials on the proliferation and differentiation of osteoblastsExp.1 Effect of rhBMP2 combined with artificial bone substitute materials on the proliferation of osteoblastsMethods and Methods:The osteoblasts were primary cultured from the calvarias of 24h newborn SD rat by modified collagenase digestion method. The third generation cells were cultured with artificial bone substitute materials combined with rhBMP-2. The effects of the materials on the proliferation of osteoblasts were detected by MTT in 3,6 and 9 days, respectively.Results:Compared with the negative control group, the ?-TCP and Bio-oss can promote the proliferation of cells. After cooperated with rhBMP-2, the new materials were much more effective than the original materials to accelerate the cell proliferation. This result indicated that the rhBMP-2 incorporated materials could effectively promote the proliferation of osteoblast.Exp.2 Effect of rhBMP-2 combined with artificial bone substitute materials on the activity of alkaline phosphatase of osteoblastsMethods and Methods:The osteoblasts were primary cultured from the calvaria of 24h newborn SD rat by modified collagenase digestion method. The third generation cells were cultured with artificial bone substitute materials combined with rhBMP-2. The effects of the materials on the ALP activity of osteoblasts were detected by ALP assay kit in 3,6 and 9 days, respectively.Results:Compared with the negative control group, the P-TCP and Bio-oss can promote the ALP activity of the osteoblasts. After cooperated with rhBMP-2, the new materials were much more effective than the original materials to accelerate the ALP activity of osteoblasts. This result indicated that the rhBMP-2 incorporated materials could effectively promote the differentiation of osteoblast. The new materials have the potential to accelerate the formation of new bone.PART TWO-The study of bone repair effect of rhBMP2 combined with artificial bone substitute materials in alveolar defect around the dental implant-an animal studyExp.3 Imaging observation of bone repair effect of rhBMP2 combined with artificial bone substitute materials in alveolar defect around the dental implantMethods and Methods:Ten healthy adult Beagle dogs were used in this study. The mandibular premolars of the dogs were extracted firstly. Three months later, dental implants were placed in the mandibular, and a 5mm*4mm*3mm bone defect area was prepared on the buccal side of each implant. The bone defect areas were filled with ?-TCP, rhBMP-2/?-TCP compound, Bio-Oss or rhBMP-2/Bio-Oss compound respectively. The bone defect areas were filled nothing as the blank. The dogs were sacrificed after 4 or 12 weeks. Samples were prepared for the gross observation and X-ray analysis.Results:The new bone formation was observed in all experiment groups. After 4 weeks, the bone density of materials combined with rhBMP-2 groups (36.70±1.73% and 38.50±1.83%) were higher than the raw materials groups (30.50±1.81% and 31.48±1.86%). After 12 weeks, the bone density of materials combined with rhBMP-2 groups (52.84±1.85% and 54.85±1.87%) were also higher than the raw materials groups (43.65±1.81% and 44.94±1.88%).Exp.4 Histological observation of bone repair effect of rhBMP2 combined with artificial bone substitute materials in alveolar defect around the dental implantMethods and Methods:Ten healthy adult Beagle dogs were used in this study. The mandibular premolars of the dogs were extracted firstly. Three months later, dental implants were placed in the mandibular, and a 5mm*4mm*3mm bone defect area was prepared on the buccal side of each implant. The bone defect areas were filled with ?-TCP, rhBMP-2/?-TCP compound, Bio-Oss or rhBMP-2/Bio-Oss compound respectively. The bone defect areas were filled nothing as the blank. The dogs were sacrificed after 4 or 12 weeks. Samples were prepared for histomorphology analysis.Results:The new bone formation was observed in all experiment groups. After 4 weeks, the new bone formation rate of materials combined with rhBMP-2 groups (30.32±1.38% and 32.46±1.26%) were higher than the raw materials groups (22.05 ±1.24% and 24.05±1.27%). After 12 weeks, the new bone formation rate of materials combined with rhBMP-2 groups (58.08±1.30% and 65.28±1.23%) were also higher than the raw materials groups (48.05±1.23% and 53.15±1.36%).PART THREE-Clinical efficacy of the bone repair effect of rhBMP-2 combined with Bio-oss in alveolar defect around the dental implantExp.5 Clinical efficacy of the bone repair effect of rhBMP-2 combined with Bio-oss in alveolar defect around the dental implantMethods and Methods:40 patients were selected in this study. And the 40 cases were randomly divided into two groups. After the implants were implanted in the alveolar bone, Bio-oss or rhBMP-2/Bio-oss complexes was placed in the bone defect area.7 days later wound healing was observed. X-ray was taken to measure the quality of new bone formation in the two groups of at postoperative day, and three months later respectively.Results:The soft tissue wounds of all patients were healed a week later. X-rayanalysis results showed that the new bone formation ability of rhBMP-2/Bio-Oss complex was higher than Bio-oss group. It could complete the repair of bone defects in a shorter time.Conclusions:1. The results of cytological test showed that rhBMP-2 incorporated material can effectively promote the proliferation and differentiation of osteoblasts.2. rhBMP-2 combined with artificial bone substitute materials could effectively promote new bone formation of the bone defect area around implant in dogs.3. rhBMP-2 can effectively improve the bone repair ability of Bio-oss in peri-implant bone defect area in human.4. rhBMP-2 and combined with the artificial bone substitute materials can promote the repair of peri-implant bone defects effectively. It provides a new way for the treatment of peri-implan bone defects.Within the limitation of this study, it could be concluded that rhBMP-2 can effectively promote the peri-implant bone defect repairment. It provides an effective method to improve the success rate of implant supported restorations. However, the specific mechanism and clinical effects need to be further explored. |
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