Bone substitute material implantation has become an important treatment strategy for the repair of oral and maxillofacial bone defects. Recent studies have shown that appropriate inflammatory and immune cells are essential factors in the process of osteoinduction of bone substitute materials. Previous studies have mainly focused on innate immune cells such as macrophages. In our previous work, we found that T lymphocytes, as adaptive immune cells, are also essential in the osteoinduction procedure. As the most important antigen-presenting cell, whether dendritic cells (DCs) can recognize non-antigen biomaterials and participate in osteoinduction was still unclear. In this study, we found that surgical trauma associated with materials implantation induces necrocytosis, and this causes the release of high mobility group protein-1 (HMGB1), which is adsorbed on the surface of bone substitute materials. Subsequently, HMGB1-adsorbed materials were recognized by the TLR4-MYD88-NFκB signal axis of dendritic cells, and the inflammatory response was activated. Finally, activated DCs release regeneration-related chemokines, recruit mesenchymal stem cells, and initiate the osteoinduction process. This study sheds light on the immune-regeneration process after bone substitute materials implantation, points out a potential direction for the development of bone substitute materials, and provides guidance for the development of clinical surgical methods.
Biocompatible Materials/metabolism* ; HMGB1 Protein/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Bone Substitutes/metabolism* ; Dendritic Cells/metabolism*

In the process of repairing of bone defects, bone scaffold materials need to be implanted to restore the corresponding tissue structure at the injury. At present, the repair materials used for bone defects mainly include autogenous bone, allogeneic bone, metal materials, bioceramics, polymer materials and various composite materials. Different materials have demonstrated strong reconstruction ability in bone repair, but the ideal bone implants in the clinic are still yet to be established. Except for autogenous bone, other materials used in bone defect repair are unable to perfectly balance biocompatibility, bone formation, bone conduction and osteoinduction. Combining the latest advances in materials sciences and clinical application, we believe that composite materials supplementedwith Chinese medicine, tissue cells, cytokines, trace elements, etc. and manufactured using advanced technologies such as additive manufacturing technology may have ideal bone repair performance, and may have profound significance in clinical repair of bone defects of special type. This article reviewed to the domestic and foreign literature in recent years, and elaborates the current status of bone defect repair materials in clinical application and basic research in regard to the advantages, clinical options, shortcomings, and how to improve the autogenous bone, allogeneic bone and artificial bone materials, in order to provide a theoretical basis for clinical management of bone defects.
Acrylic Resins ; Biocompatible Materials ; Bone Substitutes ; Bone and Bones ; Osteogenesis ; Tissue Engineering ; Tissue Scaffolds

OBJECTIVE: To evaluate the effect of two barrier membranes [multilaminated small intestinal submucosa (mSIS) and bioresorable collagen membrane (Bio-Gide)] combined with deproteinized bovine bone mineral Bio-Oss on guided bone regeneration through a canine extraction sockets model. METHODS: The distal roots of 18 premolars of the Beagle' s bilateral maxillary and mandibular were removed, and 18 extraction sockets were obtained. They were randomly divided into 3 groups, and the following procedures were performed on the sockets: (1) filled with Bio-Oss and covered by mSIS (mSIS group), (2) filled with Bio-Oss and covered by Bio-Gide (BG group), (3) natural healing (blank control group). Micro-computed tomograph (Micro-CT) was performed 4 and 12 weeks after surgery to eva-luate the new bone regeneration in the sockets of each group. RESULTS: The postoperative healing was uneventful in all the animals, and no complications were observed through the whole study period. Micro-CT analysis showed that the new bone fraction in the mSIS group and the BG group was significantly higher than that in the blank control group at the end of 4 weeks and 12 weeks (P < 0.05), and more new bone fraction was observed in the mSIS group than in the BG group, but the difference was not statistically significant (P>0.05). The new bone fraction of coronal third part of the socket in the mSIS group and BG group at the end of 4 weeks were significantly higher than that of the middle and apical third part of each group (P < 0.05). The values of bone mineral density were similar at 4 weeks in all the groups (P>0.05), but were significantly higher than that in the control group at the end of 12 weeks (P < 0.05). The bone morphometric analysis showed that the trabecular number and trabecular spacing were significantly better in the mSIS group and the BG group than in the control group at the end of 4 weeks and 12 weeks (P < 0.05), while the value in the mSIS group was slightly higher than in the BG group, but the difference was not statistically significant (P>0.05). The difference in trabecular thickness between all the groups was not statistically significant (P>0.05). CONCLUSION mSIS membrane as a barrier membrane combined with deproteinized bovine bone mineral can enhance new bone formation in canine extraction sockets, similar to Bio-Gide collagen membrane.
Animals ; Bone Regeneration ; Bone Substitutes ; Cattle ; Dogs ; Membranes, Artificial ; Minerals ; Tooth Extraction ; Tooth Socket/surgery* ; X-Ray Microtomography

OBJECTIVES: To evaluate the repairing ability of nano-pearl powder bone substitute in rabbit with defect of distal femur bone. METHODS: Thirty-two New Zealand rabbits were randomly divided into four groups: a nano-pearl powder/recombinant human bone morphogenetic protein 2 (rhBMP-2)/hyaluronic acid group, a nano-pearl powder/hyaluronic acid group, a nano-pearl powder group and a blank control group (=8 in each group). A defect with the diameter of 7 mm and height of 10 mm was prepared at the distal femoral metaphysis line of the rabbit.Different bone substitutes were planted, and the effect of repair was evaluated by macroscopic observation, imaging examination, and histopathological examination. RESULTS: The results of imageology showed that: the bone repairing effect in the nano-pearl powder/rhBMP-2/hyaluronic acid group was better than that in the pure pearl powder group and the nano-pearl powder/hyaluronic acid group, and which in the 3 experimental groups was better than that in the blank control group; The results of histology showed that: at the 4th, 8th and 12th weeks after the modeling operation, the speed of bone repair in the nano-pearl powder/rhBMP-2/hyaluronic acid group was faster than that in the pure pearl powder group and the nano-pearl powder/hyaluronic acid group, and which in the blank control group was far slower than that in the 3 experimental groups. The results of immunohistochemistry staining for osteocalcin antibody showed that: the osteogenic effect in the nano-pearl powder/rhBMP-2/hyaluronic acid group was better than that in the pure pearl powder group and the nano-pearl powder/hyaluronic acid group (both <0.05); there was no significant difference between the nano-pearl powder/hyaluronic acid group and the pure pearl powder group (>0.05); however, there was significant difference between the pure pearl powder group and the blank control group (<0.05). According to the staining results of Type I collagen antibody, there was no significant difference in the osteogenic effect between the nano-pearl powder/rhBMP-2/hyaluronic acid group and the nano-pearl powder/hyaluronic acid group (>0.05), but the osteogenic effect in the nano-pearl powder/hyaluronic acid group was better than that in the pure pearl powder group and the blank control group (both <0.05). CONCLUSIONS Nano-pearl powder and its bone substitute can promote the repair of bone defect, and the nano-pearl powder which contains rhBMP-2 has better osteogenic and repairing effect on defect.
Animals ; Bone Morphogenetic Protein 2 ; Bone Substitutes ; Collagen ; Femur ; Humans ; Osteogenesis ; Powders ; Rabbits ; Recombinant Proteins ; Transforming Growth Factor beta

OBJECTIVE: To evaluate the short-term outcome of regenerative surgery for peri-implantitis therapy. METHODS: From March 2018 to January 2019, 9 patients with 10 implants who suffered from peri-implantitis were included in the present research. Vertical bone defect at least 3mm in depth with 2 or more residual bone walls was confirmed around each implant by radiographic examination. Restorations were replaced by healing abutments on 3 implants with the consent of the patients. Guided bone regeneration surgery was performed after a hygienic phase. During surgery, full thickness flaps were elevated on both buccal and lingual aspects. Titanium curette was used for inflammatory granulation tissue removal and implant surface cleaning. The implant surface was decontaminated by chemical rinsing with 3% hydrogen peroxide solution. After being thoroughly rinsed with saline, the bone substitutes were placed in bone defects which were covered by collagen membranes. 6 months after non-submerged healing, the clinical parameters including peri-implant probing depth (PD, distance between pocket bottom and peri-implant soft tissue margin) and radiographic bone level (BL, distance form implant shoulder to the first bone-to-implant contact) were used to evaluate the regenerative outcome. PD was measured at six sites (mesial, middle and distal sites at both buccal and lingual aspects) around each implant, and BL was measured at the mesial and distal surfaces of each implant on a periapical radiograph. RESULTS: The deepest PD and largest BL of each implant ranged from 6-10 mm and 3.2-8.3 mm respectively. All the implants healed uneventfully after surgery. The mean peri-implant PD at baseline and 6 months after surgery were (6.2±1.4) mm and (3.1±0.6) mm respectively, and a mean (3.0±1.5) mm radiographic bone gain was observed, P<0.01. Treatment success was defined as: no sites with residual PD≥6 mm, no bleeding on probing, and BL elevation of at least 1 mm. Nine implants from 8 patients fulfilled the success criteria. Residual pockets with 6 mm in depth and bleeding on probing could be detected in only one implant. CONCLUSION Within the limitation of the present research, guided bone regeneration surgery can be used for the treatment of bone defect that resulted from peri-implantitis. Significant PD reduction and radiographic bone gain can be obtained after 6 months observation.
Alveolar Bone Loss ; Bone Substitutes ; Collagen ; Dental Implants ; Humans ; Peri-Implantitis ; Surgical Flaps ; Treatment Outcome

BACKGROUND: Tissue engineering represents a promising approach for the production of bone substitutes. The use of perfusion bioreactors for the culture of bone-forming cells on a three-dimensional porous scaffold resolves mass transport limitations and provides mechanical stimuli. Despite the recent and important development of bioreactors for tissue engineering, the underlying mechanisms leading to the production of bone substitutes remain poorly understood. METHODS: In order to study cell proliferation in a perfusion bioreactor, we propose a simplified experimental set-up using an impermeable scaffold model made of 2 mm diameter glass beads on which mechanosensitive cells, NIH-3T3 fibroblasts are cultured for up to 3 weeks under 10 mL/min culture medium flow. A methodology combining histological procedure, image analysis and analytical calculations allows the description and quantification of cell proliferation and tissue production in relation to the mean wall shear stress within the bioreactor. RESULTS: Results show a massive expansion of the cell phase after 3 weeks in bioreactor compared to static control. A scenario of cell proliferation within the three-dimensional bioreactor porosity over the 3 weeks of culture is proposed pointing out the essential role of the contact points between adjacent beads. Calculations indicate that the mean wall shear stress experienced by the cells changes with culture time, from about 50 mPa at the beginning of the experiment to about 100 mPa after 3 weeks. CONCLUSION: We anticipate that our results will help the development and calibration of predictive models, which rely on estimates and morphological description of cell proliferation under shear stress.
Bioreactors ; Bone Substitutes ; Calibration ; Cell Proliferation ; Fibroblasts ; Glass ; Methods ; NIH 3T3 Cells ; Perfusion ; Porosity ; Tissue Engineering

PURPOSE: To determine the benefits of autogenous tooth bone (ATB) graft in combination with platelet-rich plasma (PRP) in the rates of success and survival of dental implants placed simultaneously with maxillary sinus floor augmentation (MSFA). MATERIALS AND METHODS: Patients who visited the Department of Oral and Maxillofacial Surgery at Ulsan University Hospital from 2012 to 2014 and underwent simultaneous placement of implants with MSFA using ATB plus PRP were included in the study. Success and survival rates of the implants were evaluated based on the parameters of age and sex of the patient, site, follow-up period, residual bone height before surgery, diameter, and length of implant, sinus mucosa impairment, and postoperative complications. RESULT: A total of 23 patients and 67 implants were included in this study. The average age of the patients was 53.78±10.00 years. The average follow-up period after installation of the prosthesis was 53±5 months. The success and survival rates of the implants after placement of prosthesis were 95.52% and 97.01%, respectively. CONCLUSION: Combination of ATB and PRP showed high overall success rate, and it can be concluded that this combination is a predictable bone graft procedure for MSFA.
Bone Substitutes ; Dental Implantation ; Dental Implants ; Follow-Up Studies ; Humans ; Maxillary Sinus ; Mucous Membrane ; Platelet-Rich Plasma ; Postoperative Complications ; Prostheses and Implants ; Sinus Floor Augmentation ; Surgery, Oral ; Survival Rate ; Tooth ; Transplants ; Ulsan

PURPOSE: The purpose of this study was to elucidate the efficacy and safety of carbonate apatite (CO₃Ap) granules in 2-stage sinus floor augmentation through the radiographic and histomorphometric assessment of bone biopsy specimens.METHODS: Two-stage sinus floor augmentation was performed on 13 patients with a total of 17 implants. Radiographic assessment using panoramic radiographs was performed immediately after augmentation and was also performed 2 additional times, at 7±2 months and 18±2 months post-augmentation, respectively. Bone biopsy specimens taken from planned implant placement sites underwent micro-computed tomography, after which histological sections were prepared.RESULTS: Postoperative healing of the sinus floor augmentation was uneventful in all cases. The mean preoperative residual bone height was 3.5±1.3 mm, and this was increased to 13.3±1.7 mm by augmentation with the CO₃Ap granules. The mean height of the augmented site had decreased to 10.7±1.9 mm by 7±2 months after augmentation; however, implants with lengths in the range of 6.5 to 11.5 mm could still be placed. The mean height of the augmented site had decreased to 9.6±1.4 mm by 18±2 months post-augmentation. No implant failure or complications were observed. Few inflammatory cells or foreign body giant cells were observed in the bone biopsy specimens. Although there were individual differences in the amount of new bone detected, new bone was observed to be in direct contact with the CO₃Ap granules in all cases, without an intermediate layer of fibrous tissue. The amounts of bone and residual CO₃Ap were 33.8%±15.1% and 15.3%±11.9%, respectively.CONCLUSIONS: In this first demonstration, low-crystalline CO₃Ap granules showed excellent biocompatibility, and bone biopsy showed them to be replaced with bone in humans. CO₃Ap granules are a useful and safe bone substitute for two-stage sinus floor augmentation.
Apatites ; Biopsy ; Bone Substitutes ; Carbon ; Dental Implants ; Giant Cells, Foreign-Body ; Humans ; Individuality ; Prospective Studies ; Sinus Floor Augmentation

PURPOSE: This study was designed to observe the resorption pattern of biphasic calcium phosphate (BCP) used for maxillary sinus augmentation over a 3- to 6-year healing period, and to investigate factors affecting the resorption of BCP. METHODS: A total of 47 implants placed in 27 sinuses of 22 patients were investigated. All patients had residual bone height less than 5 mm at baseline. The modified Caldwell-Luc approach was used to elevate the maxillary sinus membrane, and the sinus cavity was filled with BCP (70% hydroxyapatite and 30% β-tricalcium phosphate). Implant placement was done simultaneously or in a staged manner. Serial radiographic analysis was performed up to 6 years postoperatively. RESULTS: During the follow-up period, no implant loss was reported. The mean reduced height of the augmented sinus (RHO) was 0.27±1.08 mm at 36 months, and 0.89±1.39 mm at 72 months postoperatively. Large amounts of graft material (P=0.021) and a long healing period (P=0.035) significantly influenced the amount of RHO. In particular, there was a significant relationship between a healing period longer than 40 months and RHO. CONCLUSIONS: BCP can achieve proper dimensional stability with minimal reduction of the graft height in a 3- to 6-year healing period after maxillary sinus augmentation. The healing period and the amount of graft material influenced the resorption of BCP.
Bone Substitutes ; Calcium ; Dental Implants ; Durapatite ; Follow-Up Studies ; Humans ; Maxillary Sinus ; Membranes ; Sinus Floor Augmentation ; Transplants

PURPOSE: To assess the influence of using different combinations of guided bone regeneration (GBR) materials on volume changes after wound closure at peri-implant dehiscence defects. METHODS: In 5 pig mandibles, standardized bone defects were created and implants were centrally placed. The defects were augmented using different combinations of GBR materials: xenogeneic granulate and collagen membrane (group 1, n=10), xenogeneic granulate and alloplastic membrane (group 2, n=10), alloplastic granulates and alloplastic membrane (group 3, n=10). The horizontal thickness was assessed using cone-beam computed tomography before and after suturing. Measurements were performed at the implant shoulder (HT0) and at 1 mm (HT1) and 2 mm (HT2) below. The data were statistically analysed using the Wilcoxon signed-rank test to evaluate within-group differences. Bonferroni correction was applied when calculating statistical significance between the groups. RESULTS: The mean horizontal thickness before suturing was 2.55±0.53 mm (group 1), 1.94±0.56 mm (group 2), and 2.49±0.73 mm (group 3). Post-suturing, the values were 1.47±0.31 mm (group 1), 1.77±0.27 mm (group 2), and 2.00±0.48 mm (group 3). All groups demonstrated a loss of horizontal dimension. Intragroup changes exhibited significant differences in group 1 (P < 0.001) and group 3 (P < 0.01). Intergroup comparisons revealed statistically significant differences of the relative changes between groups 1 and 2 (P=0.033) and groups 1 and 3 (P=0.015). CONCLUSIONS: Volume change after wound closure was minimized by using an alloplastic membrane. The stability of the augmented horizontal thickness was most ensured by using this type of membrane irrespective of the bone substitute material used for membrane support.
Alveolar Ridge Augmentation ; Bone Regeneration ; Bone Substitutes ; Collagen ; Cone-Beam Computed Tomography ; In Vitro Techniques ; Mandible ; Membranes ; Shoulder ; Wounds and Injuries