TRAF6 promotes osteogenesis in ADSCs through Raf-Erk-Merk-Hif1-a pathway.

Critical-size defects (CSDs) are challenging oral clinical issues that need to be solved. Adipose-derived mesenchymal stem cells (ADSCs) and gene therapy offer a new target to solve these issues. Consequently, ADSCs attract more and more attention because of advantages such as easy obtainability and no ethical concerns. TNF receptor-associated factor 6 (TRAF6) is a significant binding protein both of tumour necrosis factor superfamily and of the toll/interleukin-1 receptor superfamily. Evidence is accumulating that TRAF6 inhibited osteoclast formation and promoted the proliferation of multiple myeloma cell lines and bone resorption. Here, we reported that overexpression of TRAF6 enhanced the proliferation, migration and osteogenesis of ADSCs through Raf-Erk-Merk-Hif1a pathway. Cell sheet of ADSCs combined with TRAF6 accelerated the healing of CSDs. In a word, TRAF6 enhanced osteogenesis, migration and proliferation through Raf-Erk-Merk-Hif1a pathway.

[Insights into peri-implantitis and its prevention].

Peri-implantitis is one of the most common complications in dental implant treatment. Peri-implantitis is a crucial implication of implant failure, which is characterized by high morbidity and intractability. Thus, how to understand peri-implantitis correctly and deeply, and how to prevent its occurrence, are important problems that every dental implant surgeon has to face.

Influences of Schneiderian membrane conditions on the early outcomes of osteotome sinus floor elevation technique: a prospective cohort study in the healing period.

OBJECTIVES: To radiographically investigate early outcomes of osteotome sinus floor elevation in the healing phase utilizing cone beam computed tomography and evaluate influences of Schneiderian membrane conditions. MATERIAL AND METHODS: One hundred patients were consecutively recruited for osteotome sinus floor elevation (OSFE) surgery using deproteinized bone mineral. CBCT was taken prior to (T0), immediately post-operatively (T1), and after the healing period (T2). Linear and volumetric measurements of the elevated region from T0 to T1 were performed for evaluation on computed tomography (CT). RESULTS: Osteotome sinus floor elevation were performed in 100 patients. One implant of each patient was selected. Mean residual bone height (RH) was 7.21 ± 1.12 mm. Mean sinus floor elevation height (SE) was 4.81 ± 0.75 mm. The mean endo-sinus bone gain after the healing period was 3.25 ± 0.83 mm. Pre-opterative CBCT scans revealed that 72 patients had a normal sinus membrane in osteotome region, 13 patients presented with flat thickened mucosa and 15 patients with antral pseudocysts. There is no significant difference in sinus mucosa elevation height, bone graft volume and new bone formation in group of Thickening membrane and Antral pseudocysts compared with normal. CONCLUSIONS: The radiographical results show that OSFE is a safe and predictable surgical procedure in residual bone height of 7.21 ± 1.12 mm. Mild flat thickening (>2 and <5 mm) and antral pseudocysts in a small size without clinical symptoms may not be contraindications to OSFE surgery.

Longitudinal response of membrane thickness and ostium patency following sinus floor elevation: a prospective cohort study.

OBJECTIVES: To investigate the influence of sinus floor elevation (SFE) on sinus physiology, including Schneiderian membrane thickness (MT) and ostium patency, using cone beam computed tomography (CBCT). MATERIALS AND METHODS: Based on pre-established selection criteria, 53 patients in combination with 53 sinuses were referred for SFE with a lateral approach using deproteinized bone mineral. CBCT was performed prior to, immediately after surgery and before staged implant placement. The Schneiderian MT of the elevated region, ostium patency, and other clinical data was evaluated. RESULTS: The two-stage sinus augmentation technique was applied in 33 males and 20 females. Four membrane perforations were observed during the surgical procedure. The Schneiderian membrane exhibited significant swelling immediately after augmentation (P < 0.0001), but this difference disappeared after a mean healing period of 7.51 months. The corresponding changes were also observed for ostium patency with a tendency of transient obstruction after surgery. Sinuses with flat mucosal thickening or pseudocysts did not present a liability of perforation compared to the normal cases, and the augmentation procedure was not likely to deteriorate the pathology of mucosal thickening or pseudocysts. CONCLUSIONS: The results show that SFE with a lateral approach has no significant influence on MT and ostium patency after the healing period except for postoperative transient swelling and obstruction. Thickened membranes and antral pseudocysts in a small size might not be contraindications to SFE from the standpoint of the surgical impact on the Schneiderian membrane.

Ridge expansion alone or in combination with guided bone regeneration to facilitate implant placement in narrow alveolar ridges: a retrospective study.

OBJECTIVE: To evaluate the long-term outcomes of ridge expansion technique in dealing with horizontal bony insufficiency of alveolar ridges for implant placement. MATERIALS AND METHODS: During the period 2004-2009, 168 patients with width insufficiency of alveolar ridges were treated using the ridge expansion technique to obtain an improved bony base for implant placement. Depending on the severity of width insufficiency, the surgical procedures were classified into two groups: ridge expansion alone (Group 1) and ridge expansion in combination with guided bone regeneration (Group 2). After 4-6 months of unloaded healing, the implants were restored. The patients were followed up until 2013 with clinical and radiographic examinations. RESULTS: Among the 168 patients, 11 patients underwent a fracture of labial/buccal bony plate during surgery, which was corrected by changing the procedure into bone grafting, yielding a surgical failure rate of 6.5%. In the remaining 157 patients successfully treated by ridge expansion alone or in combination with GBR, 226 implants were simultaneously placed as planned. No implant failed over 2.8 years (6 months to 8 years) of follow-up, yielding a cumulative implant survival rate of 100% in each group. Six implants in Group 1 and 4 implants in Group 2, although osseointegrated and in function, did not fulfill success criteria: Cumulative implants' success rates were 93.2% in Group 1 and 95.6% in Group 2. The mean marginal bone losses during the first year in Group 1 and Group 2 were 0.69 and 0.43 mm, respectively, followed by an annual loss of ~ 0.06 and 0.07 mm, respectively, in the following years. No clinical parameter was abnormal. Twenty-two (10.4%) implants were exposed to peri-implant mucositis, whereas 19 (11.0%) implant-supported restorations were involved in prosthetic complications. CONCLUSIONS: The preliminary results of this retrospective study indicate that ridge expansion alone or in combination with GBR can be considered an effective and safe procedure for treatment of width insufficiency of alveolar ridges on the purpose of implant application.

[Maxillary sinus floor augmentation with Bio-Oss as a sole graft: a histologic, radiographic and preliminary clinical study].

OBJECTIVE: To evaluate new bone formation and preliminary clinical outcomes following maxillary sinus floor augmentation with Bio-Oss alone. METHODS: Nine patients were treated with ten maxillary sinus floor augmentations using Bio-Oss alone, and eighteen Straumann implants were placed. After five to eleven-month healing period at implant placement, cylindrical specimens were biopsied from the augmented area. The new bone formation of specimens was analyzed by histology and micro-computed tomography. Cone beam computed tomography (CBCT) scans were performed for measurements of residual crestal bone height under the sinus, the amount of increased height immediate after the augmentation and before implant insertion. To monitor stability changes, resonance frequency analysis was performed and implant stability quotient (ISQ) values were collected at implant placements (baseline,0 month), one month, three months and six months after placements. RESULTS: All implants were loaded six months after insertion and no failures were recorded. Compared to adjacent native bone, no significant differences of bone volume fraction were found in augmented area (P > 0.05), together with lower trabecular number (P < 0.05) and trabecular thickness (P < 0.01) as well as higher trabecular separation (P < 0.01) by microradiographic analysis.Histomorphometrically, there was no significant difference in the amount of new bone formation between the adjacent native bone and augmented area (P > 0.05). CBCT showed a bone height gain of (14.19 ± 2.02) mm immediate after augmentation, which stabilized at (13.68 ± 1.95) mm after bone healing period. Mean ISQ value was 71.94 ± 6.51 at baseline, decreased to 70.19 ± 6.38 at 1 month, and increased to 78.17 ± 3.83 at 3 month and 82.56 ± 3.20 at 6 month. CONCLUSIONS: The use of Bio-Oss as the sole graft is reliable and can lead to satisfactory bone formation and clinical outcome.

Effects of local delivery of bFGF from PLGA microspheres on osseointegration around implants in diabetic rats.

OBJECTIVE: Diabetes mellitus may impair bone healing after dental implant placement. The objective of this study was to evaluate the effects of the local delivery of basic fibroblast growth factor (bFGF) from poly(lactide-co-glycolide) (PLGA) microspheres on osseointegration around titanium implants in diabetic rats. STUDY DESIGN: The bFGF-PLGA microspheres were prepared by the W/O/W double-emulsion solvent evaporation method. A total of 20 rats were used to create diabetic animal models by giving them a high-fat and high-sugar diet and a low-dose streptozotocin intraperitoneal injection. Titanium implants were planted into the tibias of the diabetic rats and into 10 normal rats. Microspheres were loaded on the surfaces of the implants in the bFGF intervention group before they were placed into the rats. After 4 or 8 weeks, the tibias containing the implants were removed and embedded with resin. Uncalcified tissue slices were prepared to compare osseointegration. RESULTS: At 4 weeks, the bone-implant contact rate in the diabetic control group was less than that in the control group and the bFGF intervention group (P < .05). At 8 weeks, the results among the 3 groups were similar to those at 4 weeks. CONCLUSIONS: The local delivery of bFGF from PLGA microspheres into areas around titanium implants may improve osseointegration in diabetic rats.

In vitro culture and characterization of alveolar bone osteoblasts isolated from type 2 diabetics

In order to understand the mechanisms of poor osseointegration following dental implants in type 2 diabetics, it is important to study the biological properties of alveolar bone osteoblasts isolated from these patients. We collected alveolar bone chips under aseptic conditions and cultured them in vitro using the tissue explants adherent method. The biological properties of these cells were characterized using the following methods: alkaline phosphatase (ALP) chemical staining for cell viability, Alizarin red staining for osteogenic characteristics, MTT test for cell proliferation, enzyme dynamics for ALP contents, radio-immunoassay for bone gla protein (BGP) concentration, and ELISA for the concentration of type I collagen (COL-I) in the supernatant. Furthermore, we detected the adhesion ability of two types of cells from titanium slices using non-specific immunofluorescence staining and cell count. The two cell forms showed no significant difference in morphology under the same culture conditions. However, the alveolar bone osteoblasts received from type 2 diabetic patients had slower growth, lower cell activity and calcium nodule formation than the normal ones. The concentration of ALP, BGP and COL-I was lower in the supernatant of alveolar bone osteoblasts received from type 2 diabetic patients than in that received from normal subjects (P < 0.05). The alveolar bone osteoblasts obtained from type 2 diabetic patients can be successfully cultured in vitro with the same morphology and biological characteristics as those from normal patients, but with slower growth and lower concentration of specific secretion and lower combining ability with titanium than normal ones.

In vitro culture and characterization of alveolar bone osteoblasts isolated from type 2 diabetics.

In order to understand the mechanisms of poor osseointegration following dental implants in type 2 diabetics, it is important to study the biological properties of alveolar bone osteoblasts isolated from these patients. We collected alveolar bone chips under aseptic conditions and cultured them in vitro using the tissue explants adherent method. The biological properties of these cells were characterized using the following methods: alkaline phosphatase (ALP) chemical staining for cell viability, Alizarin red staining for osteogenic characteristics, MTT test for cell proliferation, enzyme dynamics for ALP contents, radio-immunoassay for bone gla protein (BGP) concentration, and ELISA for the concentration of type I collagen (COL-I) in the supernatant. Furthermore, we detected the adhesion ability of two types of cells from titanium slices using non-specific immunofluorescence staining and cell count. The two cell forms showed no significant difference in morphology under the same culture conditions. However, the alveolar bone osteoblasts received from type 2 diabetic patients had slower growth, lower cell activity and calcium nodule formation than the normal ones. The concentration of ALP, BGP and COL-I was lower in the supernatant of alveolar bone osteoblasts received from type 2 diabetic patients than in that received from normal subjects (P < 0.05). The alveolar bone osteoblasts obtained from type 2 diabetic patients can be successfully cultured in vitro with the same morphology and biological characteristics as those from normal patients, but with slower growth and lower concentration of specific secretion and lower combining ability with titanium than normal ones.

[Effect of sustained release of recombinant rat insulin-like growth factor-1 from poly (lactide-CO-glycolide ) microspheres on bone formation in the peri-implant areas in Goto-Kakizaki rats with type 2 diabetes].

OBJECTIVE: To evaluate the effect of sustained release of recombinant rat insulin-like growth factor-1(rrIGF-1) from poly (lactide-CO-glycolide) (PLGA) microspheres on bone formation in the peri-implant areas in Goto-Kakizaki rats with type 2 diabetes. METHODS: Type 2 diabetes models were successfully established in 20 male Goto-Kakizaki rats, which were then randomly divided into treatment group (sustained release of rrIGF-1 from PLGA microspheres were loaded on the peri-implant areas, n=10) and diabetic group (loaded with isodose placebo from PLGA microspheres, n=10). Another ten male SD rats served as control group (did not sustain any loading). Titanium implants were inserted into the tibias of 30 diabetic and normal animals. Four, 5, and 8 weeks after implantation, local blood samples around the implants were obtained for the determination of serum osteocalcin (OCN), serum bone specific alkaline phosphatase (B-ALP), and serum procollagen I carboxyterminal propeptide (PICP) with enzyme linked immunosorbent assays. RESULTS: Four weeks after implantation, OCN, B-ALP, and PICP were significantly lower in both treatment group and diabetic group than in control group(both P<0.05). Five weeks after implantation, serum OCN and B-ALP levels of the diabetic group were significantly lower than those of the other two groups (all P<0.05). Serum PICP levels of both diabetic group and treatment group were significantly lower than that of control group(both P<0.05). The OCN level in the trealment group was significantly higher in the post-operative 5th week than in the post-operative 4th week, while the PICP levels in the diabetic group were significantly lower than those in the treatment group and control group in the post-operative 8th week (both P<0.05). CONCLUSION: Sustained release of rrIGF-1 from PLGA microspheres loaded on the local peri-implant areas can promote bone formation in the peri-implant areas in Goto-Kakizaki rats with type 2 diabetes.

Sustained release of insulin-like growth factor-1 from poly(lactide-co-glycolide) microspheres improves osseointegration of dental implants in type 2 diabetic rats.

Dental implantation is an effective and predictable treatment modality for replacing missing teeth and repairing maxillofacial defects. However, implants in patients with type 2 diabetes mellitus are likely to have a high failure rate and poor initial osseointegration. In the current study, we established an effective drug delivery system designed to improve osseointegration of dental implants in an animal model of type 2 diabetes. Twenty type 2 diabetic rats were divided into two groups: a group receiving recombinant rat Insulin-like Growth Factor 1 (rrIGF-1) Microsphere Therapy (MST) (10 rats) and a control group (10 rats). The rrIGF-1 was encapsulated into poly(lactide-co-glycolide) (PLGA) microspheres to produce a sustained-release effect around titanium (Ti) dental implants in the rrIGF-1 MST group. Scanning electron microscopy, confocal laser scanning microscopy, and cumulative-release studies were conducted to verify the release effect of the microspheres as well as rrIGF-1 bioactivity. Five rats from each group were sacrificed at weeks 4 and 8 post surgery, and a histological analysis was performed on the rats from both groups. Compared to the control group, rats that received rrIGF-1 by PLGA microsphere treatment were observed to have a higher bone-implant contact percentage around the Ti implants at week 4 or week 8 post surgery (P<0.05). This result clearly indicates that sustained release of rrIGF-1 through encapsulation by PLGA microspheres positively affects osseointegration of dental implants in type 2 diabetic rats.

Type 2 diabetes mellitus impairs bone healing of dental implants in GK rats.

Type 2 diabetes is an increasingly prevalent disease with oral health manifestations. In this study, titanium implants were placed in the femora of 10 type 2 diabetic and 10 age-matched normal rats. We compared the results of bone histomorphometry around the dental implants at 4 and 8 weeks postsurgery.

[Optimized thread pitch design and stress analysis of the cylinder screwed dental implant].

OBJECTIVE: To determine the optimal thread pitch for an experimental cylinder implant in Ansys Work-bench Design Xplorer environment. METHODS: Finite element models of segment jaw bone with a V-shaped thread implant were created. The thread pitch (P) was set from 0.5 mm to 1.6 mm. The maximum Equivalent stresses (EQV stresses) in jaw bone and in implant were evaluated. RESULTS: Under axial load, the amplification of maximum EQV stresses in cortical bone, cancellous bone and implant were 7.1%, 123.4% and 28.7% respectively. Under bucco-lingual load, the amplification of maximum EQV stresses in cortical bone, cancellous bone and implant were 2.8%, 28.8% and 14.9% respectively. When P exceeded 0.8 mm, the response curve curvature of maximum EQV stresses in jaw bone and in implant to P was ranged from -1 to 1. CONCLUSION: Stresses in cancellous bone are more sensitive to thread pitch than in cortical bone. Stresses in jaw bone under axial load are easier affected by thread pitch than under bucco-lingual load. Thread pitch plays a greater role in protecting dental implant under axial load than under bucco-lingual load. Thread pitch exceed 0.8 mm should be the optimal design in a cylinder implant, but oversized pitch should be avoided too.

[Clinical research of rehabilitating bilateral total maxillary defects with a new improved implants and magnetic attachments bar frameworks: report of 9 cases].

PURPOSE: The purpose of this study was to research the clinical effects of a new improved implant-magnetic attachment bar framework supported the total maxillary prosthesis. METHODS: Nine patients underwent tumor resection with defect of bilateral maxilla, and after at least 1 year,4 implants was inserted into their bilateral zygomatics in every patient. A kind of new improved bar framework were fabricated with implants tightly. Based on these bar framework ,total maxillary prostheses were completed finally. RESULTS: The new improved bar framework was utilized to support the prosthesis, it was observed that the prosthesis was more stable. All patients were satisfied with mastication, speech and appearance after wearing the prosthesis. The prosthesis demonstrated a significant improvement in function and esthetics. CONCLUSIONS: It is concluded that from the practical point of view,the prosthesis with new bar framework is superior to the previous one, and its clinical prosperity is wide. But further studies are necessary to evaluate its long term effects.

[Study on reference value of healthy teeth mobility of youth].

OBJECTIVE: This study aimed to establish the reference value range of healthy teeth mobility in Chinese youth. METHODS: 200 right side teeth of Han nationality of Chinese youths were measured so as to get the range of the parameters. RESULTS: All parameters of 14 teeth were achieved. The parameter of TM in mandibular incisor was the highest and in mandibular first molar lowest. CONCLUSION: It is very significant to get and quantify the healthy teeth's parameter range. Because they can be served as the healthy contrast when dentists diagnose the mobility. It also reflects the fact that lower the TM parameter is, firmer the tooth will be.

[Analysis of patient's satisfaction with the mandibular implant-borne overdentures].

OBJECTIVE: To compare the subjective attitudes of fully edentulous patients in mandible toward the implant-borne overdentures and toward the previous complete dentures. METHODS: 16 fully edentulous patients in mandible were consecutively included in this study and the attitudes toward the implant-borne overdentures and the previous complete dentures were surveyed through questionnaires at the first visit and after the implant prosthesis. RESULTS: There exists significant difference regarding to the comfort, function and fixedness between implant-borne overdentures and the previous complete denture. CONCLUSION: It was revealed that mandibular bar-clip retention implant-borne overdentures can highly fulfill patient's demands.

[Improvement of osseointegration of titanium dental implants by a modified sandblasted surface].

OBJECTIVE: To study effects of the modified sandblasted surface of titanium implants, developed by authors, on the bone healing process. METHODS: Osteoblasts were derived from the 5th passage of human fetal osteoblasts after primary isolation. Alkaline phosphatase (ALP) activities and protein contents of cellular layers, and osteocalcin contents in culturing medium were employed as criteria to evaluate osteogenic functions and differentiation of osteoblasts. The ALP activity was assayed utilizing the kinetic method, the protein content utilizing the Coomassie's method, and the osteocalcin content utilizing the radioimmune assay (RIA) method. Values of all criteria were divided by the corresponding cell numbers of different groups at a respective time point for the purpose of standardization. Samples were assigned to three groups-the modified sandblasted surface group, the smooth surface group and the blank control group, The culture was ended at, 4 days and 13 days. RESULTS: At 4 days of culture, the modified sandblasted surface group showed a superiority to the smooth group with respects to the ALP activity [(17.390 +/- 1.595) nmol PNP x min(-1) x 10(-6) cells vs. (10.978 +/- 1.879) nmol PNP x min(-1) x 10(-6) cells] and protein content [(152.7 +/- 16.3) micro g/10(6) cells vs. (58.0 +/- 5.9) micro g/10(6) cells] of cellular layers and the osteocalcincontent [(43.0 +/- 6.1) ng/10(6) cells vs. (24.9 +/- 6.0) ng/10(6) cells] in culturing medium. Till the 13th day of culture, no differences were detected. CONCLUSIONS: It is cytologically proved that the modified sandblasted surface can accelerate the bone healing process of implants though the improvement of osteoblastic functions and differentiation.