| Currently,direct bone grafting at the alveolar fossa left after tooth extraction is the most extensively used approach to maintain alveolar ridge height and width.This approach has many advantages including being a simple operation with low trauma,rich material sources,etc.Autogenous bone,allogeneic bone,xenogeneic bone,and a variety of artificial bones are currently available for directly grafting the alveolar fossa.Without any doubt,autologous bone is the best bone graft material and has been considered to be the gold standard among various bone grafting materials.However,a second surgery field has to be created in the patient in order to obtain autologous bone.The clinical application of autologous bone has thus been limited due to the limited volume of bone available for harvesting,difficulty in shaping the graft,and clinical complications.Recently,progress has been achieved in the research and application of xenogeneic bone to preserve alveolar ridge.Xenogeneic bone has the advantages of an abundance in sources for heterogeneous bone graft material that can be easily obtained,processed,and stored.The disadvantage is the strong immune rejection reaction in the human body to xenogeneic bone that can cause failure of the graft.Bio-Oss bone granules(de-proteinated bovine bone matrix)are currently produced by Geistlich in Switzerland.These granules are free of any organic ingredients,and thus,are very loose and fragile.They have been widely used in the clinic due to their excellent osteoconductivity as filling materials to repair bone defects.However,patients in China are not ready for them due to their high cost.Therefore,it has been an important research topic to develop domestically produced bone graft materials,as an alternative to Bio-Oss,that possess similar efficacy.The principle of GTR is to create a relatively closed tissue environment by isolating the lesion from the surrounding tissue by exploiting the membrane’s physical barrier function,thus maximizing the regeneration of the particular tissue.GTR was first used to promote bone tissue repair and regeneration.Buser et.al.proposed the concept of guided bone regeneration(GBR)in 1993.Its application provided a new and effective approach for the restoration of insufficient bones at the dental implantation area and other bone defects as well as the healing of bone fractures.Since then,GBR has become a hot research topic in the field of biology,medicine,and materials.In the clinic,there are some patients’ bone mass decreased caused by diabetes or osteoporosis.This kind of patients,filling bone graft materials directly in the tooth socket after tooth extraction,the alveolar ridge preservation effect is poor.How to solve this problem,is a difficult problem in clinical treatment.Skeleton is a living and continuously remodeling tissue,which exhibits abundant sensory neuron innervation.Osteogenic cells alter metabolic and anabolic activities in response to the variety of systemic and local factors such as hormones and growth factors.The nerve-derived factors are capable of modulating cellular activities of the bone cells.Many of the nerve-derived factors that may act as efferent agents to the bone cells fall into the category of neuropeptides.Neuropeptide substance calcitonin gene-related peptide(CGRP)and substance P(SP)can inhibit the bone resorption activity of osteoclasts and promote the osteogenic ability of osteoblasts.We can make the CGRP and SP release system,and combine with bone graft material,filling the bone defect.The drug will release slowly,promote osteogenesis,and repair the bone defect area.So we do some research foundation.This research project consisted of six experiments: Experiment 1 to test the effects of calcined bovine bone for promoting the repair of the canine tooth socket;Experiment 2 to clinically validate the effects of calcined bovine bone in the repair of jaw defects;Experiment 3 to test the effects of GTR membranes(GTRM)for promoting the repair of the canine tooth socket;Experiment 4 to clinically evaluate the effectiveness of GTRM in repairing alveolar bone defects;Experiment 5 to evaluate the effectiveness of GTRM for delayed implant placement and guiding alveolar bone defect regeneration via imaging and histological studies;and Experiment 6 to investigate the therapeutic effect of gelatin microspheres containing different concentrations of calcitonin gene-related peptide(CGRP)or substance P on repairing bone defects in a rabbit.Experiment 1: Effects of calcined bovine bone for promoting the repair of the canine tooth socketObjective: To investigate the effects of calcined bovine bone on the repair of canine tooth sockets.Methods: Eight adult dogs’ 3rd pre-molar teeth of the mandible were extracted,and the right side were rassigned to a test group(n=8)and left side is the control group(n=8).Each tooth socket was filled with CBB and then covered with Bio-Gide membrane for the test group or only Bio-Gide resorbable membrane for the control group.The roots were then closed with suturing.The dogs were clinically examined at 8 weeks post-surgery,and then imaging and histological studies were performed on the harvested tissues.Results: At 8 weeks post-surgery,the operation field had recovered well for both groups without an inflammatory reaction.Imaging studies showed that the test group had an average bone volume of 81.99±3.12% and the control group had an average bone volume of 63.44±3.34%(p<0.05).The mean thickness of trabecular bone was 0.492±0.033 mm for the test group and 0.251±0.061 mm for the control group(p<0.05).Histological results showed that the new bone was mature in a continuous state with no difference from the autologous bone in the tset group.Conclusion: There was no significant inflammatory reaction in either the test or control group.The results from histological studies were consistent with the imaging results.There has statistically significant differences in the volume of newly formed bones and bone strength between the test group and blank control group.Calcined bovine bone could function as good barriers and have a good effect of site preservation.Experimental 2: Effects of calcined bovine bone in the repair of alveolar bone defects in the clinicObjective: To evaluate the efficacy and safety of calcined bovine bone for repairing a mandibular defect after extraction and the clinical value of osteoinductive natural calcined bone in comparison to Bio-Oss absorbable bone material via imaging and clinical examination of enrolled patients.Methods: Patients were enrolled from those visiting our department in need of single tooth extraction and alveolar ridge preservation.The enrolled patients were randomly assigned to the control group or experimental group.For patients in the experimental group,the alveolar fossa was filled with calcined bovine bone after tooth extraction and then covered with Bio-Gide bioabsorbable membrane for alveolar ridge preservation.The same procedure was used for the patients in the control group except that bone graft material used was Bio-Oss bone material.At the end of 24 weeks after bone grafting,all patients received full-surface curved slice imaging and computed tomography(CT)examination to evaluate the changes in alveolar bone mass in each group.Results: A total of 257 patients completed the clinical study(127 patients in the experimental group and 130 patients in the control group).Imaging data showed that a total effectiveness rate of 93.70% was achieved in the experimental group compared with an effectiveness rate of 93.08% for the control group.In the trial group,the alveolar ridge bone height reduction was 1.22±0.42 mm,the width reduction was 1.82±0.54 mm.In the control group,the height reduction was 1.14±0.52 mm,the width reduction was 1.78±0.36 mm.That is no statistical difference in the effectiveness rates between treatment group and control group(p>0.05).Except for one patient in the control group whose wound incision healed beyond 7 days and was categorized as class B healing,the wound incision for all other patients healed completely within 7 days and was considered class A healing.No case of rejection was observed during the initial 12 weeks post-surgery.The filling materials were resorbed almost perfectly without any bone infection during the 24-week follow-up.Conclusion: Calcined bovine bone could prevent bone resorption at bone defects when used to repair jaw defects.Moreover,it could achieve defect repair without any complication or safety issues.Calcined bovine bone and Bio-Oss absorbable bone had similar effects on preserving the alveolar ridge.Experiment 3: Effects of guided tissue regeneration membrane(GTRM)for promoting the repair of the canine tooth socketObjective: To investigate the effects of GTRM on the repair of canine tooth sockets.Methods: Twelve adult dogs(six male dogs and six female dogs)were randomly assigned to a GTRM test group(n=6)and a Bio-Gide control group(n=6).The 3rd pre-molar teeth were extracted from the mandible of each dog.Each tooth socket was filled with calcined bovine bone repair material and then covered with either GTRM membrane for the GTRM test group or Bio-Gide resorbable membrane for the Bio-Gide control group.The roots were then closed with suturing.The dogs were clinically examined at 12 weeks post-surgery,and then imaging and histological studies were performed on the harvested tissues.Results: At 12 weeks post-surgery,the operation field had recovered well for both groups without an inflammatory reaction.Imaging studies showed that the GTRM group had an average bone volume of 82.06±6.52% and the Bio-Gide control group had an average bone volume of 73.91±5.62%(p>0.05).The mean thickness of trabecular bone was 0.530±0.031 mm for the GTRM group and 0.456±0.085 mm for the Bio-Gide control group(p>0.05).The bone surface area/bone volume ratio was 3.269±0.937 in the GTRM group and 4.385±0.171 in the Bio-Gide control group(p>0.05).Histological results showed that the new bone was mature in a continuous state with no difference from the autologous bone.Conclusion: There was no significant inflammatory reaction in either the GTRM or Bio-Gide group.The results from histological studies were consistent with the imaging results.No statistical differences in the volume of newly formed bones,bone strength,or bone integrity between the GTRM group and Bio-Gide group.Both GTRM and Bio-Gide membranes could function as good barriers,thus effectively achieving bone regeneration.Experiment 4: Clinically evaluating the effectiveness of GTRM in repairing alveolar bone defectsObjective: To evaluate the efficacy and safety of GTRM for regenerating alveolar bone defects via clinical trials,and to determine the clinical value of GTRM in comparison to Bio-Gide membrane.Methods: Patients were enrolled from those visiting our department in need of single tooth extraction and alveolar ridge preservation.The enrolled patients were randomly assigned to the control group or experimental group.The alveolar fossa was filled with calcined bovine bone after tooth extraction and then covered with GTRM in the experimental group or with Bio-Gide bioabsorbable membrane in the control group to preserve the alveolar ridge.All patients received panoramic radiography and CT examination immediately after surgery and at 24 weeks post-surgery to evaluate the changes in alveolar bone mass in each group.Results: A total of 252 enrolled patients completed the clinical study(126 patients in the GTRM experimental group and 126 patients in the Bio-Gide control group).Imaging evaluation showed that the total effectiveness rates were 94.44% in the experimental group and 93.65% in the control group.In the trial group,the alveolar ridge bone height reduction was 1.23±0.28 mm,the width reduction was 1.84±0.44 mm.In the control group,the height reduction was 1.15±0.39 mm,the width reduction was 1.81±0.31 mm,with no significant difference between these rates(p>0.05).At 12 and 24 weeks post-surgery,no cases of bone infection,rejection,or complications were observed in either group.Conclusion: GTRM could function as a good barrier without any complication or safety issues,thus effectively achieving bone regeneration.This material was comparable to Bio-Gide bioabsorbable membrane for preserving the alveolar ridge.Experiment 5: Evaluating the effectiveness of GTRM for the delayed implant and guiding alveolar bone defect regeneration via imaging and histological studiesObjective: To evaluate the effectiveness of GTRM for the delayed implant and guiding the regeneration of alveolar defects via imaging and histological studies.Methods: The study included patients with single tooth extraction,needed alveolar ridge preservation and delayed implant.The enrolled patients were randomly assigned to the control group or experimental group.The alveolar fossa was filled with calcined bovine bone after tooth extraction and then covered with GTRM in the experimental group or with Bio-Gide bioabsorbable membrane in the control group to preserve the alveolar ridge.Dental implants were placed at 24 weeks after alveolar ridge preservation.Bone tissue samples were harvested during the implantation procedure.Micro-CT scans and Van-Gieson(VG)staining were performed to analyze the extent of osteogenesis.And we evaluated ISQ value with RFA.Results: A total of 50 patients received dental implant restoration,including 25 cases in the experimental group and 25 cases in the control group.The ISQ value was relatively low.24 bone tissue samples were harvested,including 12 cases in the experimental group and 12 cases in the control group.Micro-CT scan results showed that there were no statistically significant differences in the bone volume fraction(BV/TV),bone surface area to bone volume ratio(BS/BV),trabecular bone number(Tb.N),trabecular bone thickness(Tb.Th),or trabecular bone separation(Tb.Sp)between the two groups(all p>0.05).Histological analysis showed that the proportions of new bone tissue were 25.035±2.342% in the experimental group and 25.347±3.221% for the control group,p>0.05.Conclusion: GTRM was comparable to Bio-Gide bioabsorbable membrane for preserving the alveolar ridge.The new bone tissue of graft area had a good effect of implant osseointegration,guaranteeing the stability of implants.Experiment 6: Gelatin microspheres containing calcitonin gene-related peptide or substance P repair bone defects in rabbitsObjective: To investigate the therapeutic effect of gelatin microspheres containing different concentrations of calcitonin gene-related peptide(CGRP)or substance P on repairing bone defects in rabbits.Methods: Different concentrations of CGRP or substance P(0.1 n M,10 n M,and 1 μM)containing gelatin microspheres were prepared and characterized in vitro before being implanted into the femur bone defects created in rabbits.Three months later,the bone defects were harvested and examined by micro-computed tomography(μ-CT)and Van Gieson staining.Results: Gelatin microspheres containing different concentrations of CGRP or substance P promoted osteogenesis after 3 months in a rabbit bone defect model.The micro-computed tomography imaging results suggested that 10 n M CGRP was optimal for increasing the trabecular number and decreasing the trabecular bone separation degree;similar effects were observed with the microspheres containing 1 μM substance P.Histological analysis showed that the gelatin microspheres containing CGRP or substance P,regardless of the concentration,effectively promoted osteogenesis,and the highest effect was achieved in the groups containing 1 μM CGRP or 1 μM substance P.Conclusion: Gelatin microspheres containing CGRP or substance P effectively promoted osteogenesis in a rabbit bone defect model dose-dependently,though their effects in repairing human alveolar ridge defects still need further investigation. |
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