Exosomes derived from reparative M2-like macrophages prevent bone loss in murine periodontitis models via IL-10 mRNA.

BACKGROUND: Periodontitis is characterized by progressive inflammation and alveolar bone loss resulting in tooth loss finally. Macrophages including pro-inflammatory M1-like macrophages and reparative M2-like macrophages play a vital role in inflammation and tissue homeostasis in periodontitis. Among them, reparative M2-like macrophages have been shown to promote tissue repair and prevent bone loss. However, the mechanism of reparative M2 macrophages-induced osteoprotective effect remains elusive. RESULTS: Exosomes from reparative M2-like macrophages (M2-Exos) were isolated and identified successfully. M2-Exos could promote bone marrow stromal cells (BMSCs) osteogenic differentiation while suppressing bone marrow derived macrophage (BMDM) osteoclast formation, and prohibit pathological alveolar bone resorption because of the intercellular communication via exosomes. High expression level of IL-10 mRNA was detected not only in reparative M2-like macrophages but also in M2-Exos. Meanwhile, IL-10 expression level in BMSCs or BMDM was also upregulated significantly after co-culturing with M2-Exos in a concentration-dependent manner. In vitro, recombinant IL-10 proteins had the ability to selectively promote osteogenic differentiation of BMSCs and hinder osteoclast differentiation of BMDM. Moreover, after treatment with M2-Exos and IL-10R antibody together, the capacity of promoting osteogenesis and suppressing osteoclastogenesis of M2-Exos was significantly reversed. In vivo experiments further showed that M2-Exos reduced alveolar bone resorption in mice with periodontitis via IL-10/IL-10R pathway. CONCLUSION: In conclusion, our results demonstrate that the reparative M2-like macrophages could promote osteogenesis while inhibiting osteoclastogenesis in vitro as well as protect alveolar bone against resorption in vivo significantly. M2-Exos could upregulate the IL-10 cytokines expression of BMSCs and BMDM via delivering exosomal IL-10 mRNA to cells directly, leading to activation of the cellular IL-10/IL-10R pathway to regulate cells differentiation and bone metabolism. These results might partly account for the mechanism of osteoprotective effect of reparative M2-like macrophages and provide a novel perspective and a potential therapeutic approach on improving alveolar resorption by M2-Exos.

Predictors of peri-implant bone remodeling outcomes after the osteotome sinus floor elevation: a retrospective study.

BACKGROUND: This study aimed to evaluate the radiographic outcomes of implants after osteotome sinus floor elevation (OSFE), and further identify the separate predictors for these radiographic outcomes. METHODS: In this retrospective cohort study, a total of 187 implants were inserted into 138 patients using the OSFE technique. Seventy-four patients in the grafted group, and 64 patients in the non-grafted group completed this study. The vertical bone gain (VBG) and marginal bone loss (MBL) at 3 years following surgery were assessed as outcome variables. Based on extensive literature results, variables considered potential predictors of outcome variables included sex, age, tooth position, implant length, implant diameter, with or without grafting materials, residual bone height, sinus width, bone density, and sinus membrane thickness. Subsequently, the binary logistic regression analysis was applied with VBG and MBL as dependent variables, respectively. The receiver operating characteristic curve (ROC) with its area under the curve (AUC) was performed to further determine the predictive value of these predictors. RESULTS: One hundred and six implants in grafted group and 81 implants in the non-grafted group were analyzed. The average VBG was 2.12 ± 1.94 mm for the grafted group and 0.44 ± 1.01 mm for the non-grafted group at 3 years (P < 0.05). The mean MBL was 1.54 ± 1.42 mm for the grafted group and 1.13 ± 1.69 mm for the non-grafted group at 3 years (P > 0.05). After the adjustment for confounders, logistic regression analysis demonstrated that implant length, grafting, residual bone height, and sinus membrane thickness were predictors of VBG. The odds ratio for VBG was 3.90, 4.04, 4.13 and 2.62, respectively. Furthermore, grafting exhibited the largest AUC at 0.80. While tooth position and implant length were predictors of MBL, the odds ratio for MBL was 3.27 and 7.85, respectively. Meanwhile, implant length exhibited the largest AUC at 0.72. CONCLUSIONS: OSFE with or without simultaneous grafting materials both showed predictable clinical outcomes. Additionally, the present study is the first quantitative and significant verification that VBG has a significant association with sinus membrane thickness, as well as residual bone height, implant length and grafting. Whereas tooth position and implant length are markedly associated with MBL.

Clinical and radiographic variables related to implants with simultaneous grafts among type 2 diabetic patients treated with different hypoglycemic medications: a retrospective study.

BACKGROUND: The influence of different hypoglycemic agents on peri-implant variables among type 2 diabetes mellitus patients is still unclear. Therefore, the aim of this study was to assess the radiographic marginal bone loss and clinical parameters around implants in patients using different hypoglycemic agents. METHODS: In this retrospective cohort study, the dental implant records of type 2 diabetes mellitus patients who met the inclusion criteria were collected. The patients using only single medication as follows: insulin, metformin, or glucagon-like peptide-1 (GLP-1) drugs, were grouped according to their medication. These patients received implant placement with the same initial status, and all the prosthesis restorations were cement-retained ceramic crowns. The peri-implant marginal bone levels were evaluated by periapical radiographs immediately after implant placement and at 1 and 2-year follow-up visits. The baseline characteristics were compared among groups. The peri-implant radiographic marginal bone loss and clinical parameters were preliminarily compared using the Kruskal-Wallis test, and then the covariates were controlled by covariance analysis. Bonferroni post hoc adjustment test was performed for the multiple comparisons. RESULTS: After a review of more than 7000 medical records, a total of 150 patients with 308 implants at 1-year follow-up were assessed. The peri-implant marginal bone loss in the GLP-1 drug group was significantly smaller than the insulin group and metformin group (P < 0.01). The radiographic bone loss in the metformin group was higher than the insulin group (P < 0.05). Some of these included patients were lost to follow-up. Only 74 patients with 129 implants completed the 2-year follow-up. The radiographic bone loss in the metformin group was still higher than the insulin group (P < 0.05) and GLP-1 group (P < 0.01). There was no significant difference in the BOP (+) and the mean PD among groups (P > 0.05). CONCLUSIONS: The radiographic variables were not exactly the same among the patients with different hypoglycemic agents at both the 1 and 2-year follow-ups. After ensuring consistency in baseline characteristics, the positive effect of GLP-1 drugs on peri-implant bone remodeling may be no less than insulin or metformin. More studies are needed to verify the direct effect of these drugs on peri-implant bone. Clinical trial registration number ChiCTR2000034211 (retrospectively registered).

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.

Construction and performance of exendin-4-loaded chitosan-PLGA microspheres for enhancing implant osseointegration in type 2 diabetic rats.

The updating and optimization of drug delivery systems is critical for better in vivo behaviors of drugs, as well as for improving impaired implant osseointegration in diabetes. Numerous studies have reported the benefits of exendin-4 on diabetic bone, with the potential to enhance osseointegration in diabetes. To construct an appropriate sustained-release system of exendin-4 targeting implant osseointegration in diabetes, this study fabricated exendin-4-loaded microspheres using poly(lactic-co-glycolic acid) (PLGA) and chitosan. The morphology, size, encapsulation efficiency, and drug release behavior of microspheres were investigated. The bioactivity of drug-loaded microspheres on cell proliferation and osteogenic differentiation of diabetic BMSCs was investigated to examine the pharmacologic action of exendin-4 loaded into chitosan-PLGA microspheres. Further, the influence of microspheres on osseointegration was evaluated using type 2 diabetes mellitus (T2DM) rat implant model. After 4 weeks, the samples were evaluated by radiological and histological analysis. The results of in vitro experiments showed that the prepared exendin-4-loaded chitosan-PLGA microspheres have good properties as a drug delivery system, and the chitosan could improve the encapsulation efficiency and drug release of PLGA microspheres. In addition, exendin-4-loaded microspheres could enhance the proliferation and osteogenic differentiation of diabetic BMSCs. The results of in vivo experiments showed the exendin-4-loaded microspheres significantly improved the impaired osseointegration and bone formation around implants in T2DM rats without affecting blood glucose levels. Thus, the local application of exendin-4-loaded chitosan-PLGA microspheres might be a promising therapeutic strategy for improving the efficacy of dental implants in T2DM individuals.

Review of ectodermal dysplasia: case report on treatment planning and surgical management of oligodontia with implant restorations.

Dental implants have proven to be a reliable modality for the rehabilitation of missing teeth. However, there are limited reports on managing anodontia related to ectodermal dysplasia in the scientific literature. The severely reduced bone quantity due to the congenital absence of multiple natural teeth is the biggest challenge for the surgeon. There are a variety of bone augmentation procedures to establish adequate bone quantity, and the surgical planning should be used on an individual case basis. This is a report of a 19-year-old male patient affected by hypohidrotic ectodermal dysplasia. Oligodontia associated with severe atrophy of jaws was the chief complaint for seeking treatment. Based on clinical and radiographic examinations, 2 bone augmentation procedures were used to obtain sufficient width of alveolus for implant placement by performing an onlay bone graft in the maxilla and vertical distraction osteogenesis in the mandible. The treatment planning was discussed and informed consent was obtained.

[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.

[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.

Inhibition of GDF11 could promote bone healing in the tooth extraction socket and facilitate mesenchymal stem cell osteogenic differentiation in T2DM pigs.

BACKGROUND: Growth differentiation factor 11 (GDF11) might be a key factor responsible for the weakening of mesenchymal stem cell (MSC) osteogenic differentiation in tooth extraction sockets in patients with type 2 diabetes mellitus (T2DM). This study aimed to confirm that inhibition of GDF11 could promote bone healing in tooth extraction sockets and facilitate MSC osteogenic differentiation under T2DM conditions. METHODS: Three streptozotocin-induced T2DM pig models and two control pig models were established. The T2DM pigs were treated with an intrasocket injection of GDF11 inhibitor in the left mandible, whereas the right side was maintained for natural healing. The postextraction socket healing of the T2DM pigs was compared with that of nondiabetic controls. Healing was quantitatively verified by microcomputed tomography, and the GDF11 expression level was detected. MSCs from T2DM pig sockets were cultured and treated with a GDF11 inhibitor. The osteogenic differentiation ability of MSCs was also compared among groups. RESULTS: The expression of GDF11 in the tooth extraction sockets from T2DM pigs increased significantly post extraction. Bone healing was promoted by periodic injection of the GDF11 inhibitor into the extraction sockets of T2DM pigs. Furthermore, the osteogenic differentiation ability of T2DM-MSCs was improved in pigs treated with the GDF11 inhibitor. CONCLUSIONS: GDF11 inhibition could promote bone healing in the tooth extraction socket and facilitate MSC osteogenic differentiation under T2DM conditions. GDF11 could be a potential therapeutic target for undesirable alveolar bone healing in T2DM patients.

Selective laser melted titanium implants play a positive role in early osseointegration in type 2 diabetes mellitus rats.

Success of dental implant is associated with the surface modification. To evaluate whether the selective laser melting-superfinished titanium (Ti6Al4V) implants have a better early osseointegration in type 2 diabetes mellitus rats compare to pure titanium implants and acid-etched treated (SLA) implants, we designed a screw-shaped implant which was batch-fabricated by selective laser melting (SLM). Then the implants were randomly inserted in tibias of rats with type 2 diabetes mellitus (T2DM). After surgical operation, the SLM group showed the best bone formation around the implants with the highest bone-implant contact rate among the three groups.Removal torque tests and histomorphological analyses all revealed a stronger connection between the bone because its good surface characteristics and mechanical properties. SLM implant may be a novel implant for T2DM patients.

Is the osseointegration of immediately and delayed loaded implants the same?--comparison of the implant stability during a 3-month healing period in a prospective study.

OBJECTIVES: The objectives of the present study were (1) to compare the stability of delayed loaded (DL) and immediately loaded (IL) ITI SLA implants during the first 3 months of the healing period using resonance frequency analysis (RFA) and (2) to determine the factors that affect implant stability during the healing period. MATERIALS AND METHODS: To compare implant stability, RFA was performed on two groups of patients (12 patients received 25 IL implants and 47 patients received 79 DL implants) with a total 104 ITI SLA implants. Implant stability was measured directly by RFA at implant placement and consecutively once a week for 12 weeks. Statistical analyses were carried out to study implant stability differences between IL and DL groups. RESULTS: One of the 25 implants in the IL group failed, and no implant was lost in the DL group. Implant stability between the IL and DL groups showed a statistically significant difference (P<0.05). The mean implant stability quotient of all measured implants from implant insertion to 12 weeks was 72.88 +/- 5.39 for the DL and 75.86 +/- 3.60 for the IL types. The lowest stability was at 4 weeks for DL implants (mean: 71.58 +/- 5.11) and 2 weeks for IL implants (mean: 71.33 +/- 2.97). In both groups, bone types I and II showed higher implant stability than bone type III (P<0.05). CONCLUSIONS: The findings of this study indicate that differences in osseointegration between IL and DL implants may be predicted according to differential implant stability.

Endodontic treatment of teeth induces retrograde peri-implantitis.

OBJECTIVES: Some cases of retrograde peri-implantitis arise from adjacent natural teeth that have peri-radicular infection. The present study was designed to investigate the incidence of retrograde peri-implantitis from adjacent teeth with endodontic treatment. MATERIALS AND METHODS: One hundred and twenty-eight patients of ages ranging from of 24-61 years were recruited for this study. A total of 128 ITI SLA implants with adjacent teeth that had received endodontic treatment at least 1 week before were placed in 128 patients. The date of endodontic therapy and the pulp status of the adjacent tooth before endodontic therapy were recorded. The distance between the implant and the adjacent tooth was determined using a radiograph. The stability of all implants was tested by OSSTELL and recorded at implant placement, after 4 and 12 weeks. RESULTS: The incidence of retrograde peri-implantitis was 7.8%. The duration from endodontic-treated adjacent teeth to implant placement was 12.15+/-10.1 weeks, and the distance between the implant and the adjacent teeth was 2.99+/-1.4 mm. Distance and time were found to be related to retrograde peri-implantitis (P<0.05). The stability of implants with retrograde peri-implantitis was less than that of the normal implants, but the difference was not significant (P>0.05). CONCLUSIONS: The incidence of retrograde peri-implantitis may reduce by increasing the distance between the implant and adjacent tooth, and/or the duration from endodontically treated adjacent tooth-to-implant placement. Although preliminary, these data might orient the practitioner to avoid retrograde peri-implantitis.

Microporous elastomeric membranes fabricated with polyglycerol sebacate improved guided bone regeneration in a rabbit model.

PURPOSE: We aimed to fabricate guided bone regeneration (GBR) membrane using polyglycerol sebacate (PGS) and investigate the impact of scaffold pore size on osteogenesis. MATERIALS AND METHODS: PGS microporous membrane was fabricated by salt-leaching technique with various pore sizes. Twenty-eight male New Zealand rabbits were randomly divided into four groups: 25 µm PGS membrane, 53 µm PGS membrane, collagen membrane, and blank control group. Subsequently, standardized and critical-sized tibia defects were made in rabbits and the defective regions were covered with the specifically prepared membranes. After 4 and 12 weeks of in vivo incubation, bone samples were harvested from tibia. Micro-computed tomography scanning was performed on all bone samples. A three-dimensional visible representation of the constructs was obtained and used to compare the ratios of the ossifying volume to total construct volume (bone volume to tissue volume [BV/TV]) of each sample in different groups; then, bone samples were stained with H&E and Masson's trichrome stain for general histology. RESULTS: At 4 weeks, the BV/TV in the 25 µm PGS group was found higher than that in the 53 µm PGS and collagen groups. At 12 weeks, the bone defect site guided by the 25 µm PGS membrane was almost completely covered by the new bone. However, the site guided by the 53 µm PGS membrane or collagen membrane was covered only most of the defects and the left part of the defect was unoccupied. Histological observation further verified these findings. CONCLUSION: We thus concluded that the 25 µm PGS membrane played an advantageous role during 4-12 weeks as compared with those earlier degraded counterparts.

Type 2 diabetes affects postextraction socket healing and influences first-stage implant surgery: A study based on clinical and animal evidence.

AIM: To verify the influence of type 2 diabetes mellitus (T2DM) on postextraction socket healing and subsequent first-stage implant surgery. MATERIALS AND METHODS: We analyzed pre-extraction and postextraction cone beam computed tomography images of T2DM patients (n = 75) and paired nondiabetic controls to investigate changes in postextraction socket and ridge dimensions. The types of guided bone regeneration (GBR) surgeries were also compared. Three T2DM pig models were established to compare their postextraction socket healing with that of nondiabetic controls. Healing was quantitatively verified by microcomputed tomography. The osteogenic differentiation of mesenchymal stem cells (MSCs) was also compared. RESULTS: Compared to nondiabetic controls, T2DM patients had higher socket width/depth values postextraction across all groups with different healing times. Among the T2DM patients, 62.7% could not receive first-stage implant surgery within 6 months postextraction, and 54.7% received GBR surgery during first-stage surgery. Ossification was not achieved in the socket center of the T2DM pig models after 3 months of healing. A decrease in osteogenic differentiation was observed in T2DM-MSCs. CONCLUSIONS: T2DM interferes with the healing of the extraction socket and thus delays first-stage implant surgery. This phenomenon may be due to the reduced osteogenic differentiation of MSCs in the sockets.

Evaluation of the cylinder implant thread height and width: a 3-dimensional finite element analysis.

PURPOSE: To evaluate continuous and simultaneous variations of thread height and width for an experimental screw-type implant. MATERIALS AND METHODS: A finite element model of an implant with a V-shaped thread was created. The range of thread height was set at 0.20 to 0.60 mm, and the range of thread width was set at 0.10 to 0.40 mm. Forces of 100 N and 50 N were applied along the implant axis (AX) and an angle of 45 degrees in a buccolingual direction (45-degree BL), respectively. The maximum von Mises stresses in jawbone were evaluated, and the sensitivity of the stress in jawbone to the variables was also evaluated. RESULTS: Under AX load, the maximum von Mises stresses in cortical and cancellous bones increased by 4.3% and 63.0%, respectively, as thread parameters changed. Under 45-degree BL load, maximum von Mises stresses in cortical and cancellous bones increased by 19.3% and 118.0%, respectively. When thread height was from 0.34 to 0.50 mm and thread width was 0.18 to 0.30 mm, the tangent slope of the maximum von Mises stress response curve ranged from -1 to 1. The variation of the maximum von Mises stresses in jawbone was more sensitive to thread height than to thread width. CONCLUSIONS: Stress in cancellous bone is more likely to be influenced by thread parameters than stress in cortical bone. A 45-degree BL force is more likely to be influenced by thread parameters than an axial force. A thread height of 0.34 to 0.50 mm and a thread width of 0.18 to 0.30 mm is optimal from a biomechanical point of view. In the design of a screw-type implant, thread height is more important than thread width for the reduction of stress within the bone.

Immediate loading for implant restoration compared with early or conventional loading: A meta-analysis.

PURPOSE: This meta-analysis was to further confirm the no inferiority of immediate loading in clinical and radiographic outcomes compared with non-immediate loadings (early or conventional loading). MATERIALS AND METHODS: Literature search on Pubmed and Embase was performed up to August 2015. The overall risk radios (RRs) and standard mean differences (SMDs) as well as their 95% confidence intervals (CI) were calculated for comparison. RESULTS: Total 29 RCT with 1342 implants receiving immediate loading and 1279 implants receiving non-immediate loadings were included in this meta-analysis. Results indicated that there was no significant difference between immediate and non-immediate loadings in implant failure rate based on patients (RR = 1.45, 95% CI: 0.79 to 2.68) and implants (RR = 1.38, 95% CI: 0.86 to 2.21), MBL (SMD = -0.11, 95% CI: -0.39 to 0.17), and ISQ (SMD = -0.26, 95% CI: -0.53 to 0.01). Meanwhile, immediate loading showed significantly less MBL change than non-immediate loading. In addition, subgroup analyses showed that the immediate loading indicated slightly higher implant failure rate and lower ISQ than conventional loading. CONCLUSIONS: Although overall analysis confirmed no inferiority of immediate loading compared with non-immediate loadings, the technique still need to be explored for improving implant success and stability during immediate loading based on the results in subgroup analyses.

The influence of direct laser metal sintering implants on the early stages of osseointegration in diabetic mini-pigs.

BACKGROUND: High failure rates of oral implants have been reported in diabetic patients due to the disruption of osseointegration. The aim of this study was to investigate whether direct laser metal sintering (DLMS) could improve osseointegration in diabetic animal models. METHODS: Surface characterizations were carried out on two types of implants. Cell morphology and the osteogenic-related gene expression of MG63 cells were observed under conditions of DLMS and microarc oxidation (MAO). A diabetes model in mini-pigs was established by intravenous injection of streptozotocin (150 mg/kg), and a total of 36 implants were inserted into the mandibular region. Micro-computed tomography (micro-CT) and histologic evaluations were performed 3 and 6 months after implantation. RESULTS: The Ra (the average of the absolute height of all points) of MAO surface was 2.3±0.3 µm while the DLMS surface showed the Ra of 27.4±1.1 µm. The cells on DLMS implants spread out more podia than those on MAO implants through cell morphology analysis. Osteogenic-related gene expression was also dramatically increased in the DLMS group. Obvious improvement was observed in the micro-CT and Van Gieson staining analyses of DLMS implants compared with MAO at 3 months, although this difference disappeared by 6 months. DLMS implants showed a higher bone-implant contact percentage (33.2%±11.2%) at 3 months compared with MAO group (18.9%±7.3%) while similar results were showed at 6 months between DLMS group (42.8%±10.1%) and MAO group (38.3%±10.8%). CONCLUSION: The three-dimensional environment of implant surfaces with highly porous and fully interconnected channel and pore architectures can improve cell spreading and accelerate the progress of osseointegration in diabetic mini-pigs.

Delivery of antagomiR204-conjugated gold nanoparticles from PLGA sheets and its implication in promoting osseointegration of titanium implant in type 2 diabetes mellitus.

Impaired osseointegration of the implant remains the big hurdle for dental implant therapy in diabetic patients. In this study, the authors first identified that miR204 was strikingly highly expressed in the bone mesenchymal stem cells (BMSCs) of diabetic rats. Forced expression of miR204 repressed the osteogenic potential of BMSCs, while inhibition of miR204 significantly increased the osteogenic capacity. Moreover, the miR204 inhibitor was conjugated with gold nanoparticles (AuNP-antagomiR204) and dispersed them in the poly(lactic-co-glycolic acid) (PLGA) solution. The AuNP-antagomiR204 containing PLGA solution was applied for coating the surface of titanium implant. Electron microscope revealed that an ultrathin sheet was formed on the surface of the implant, and the AuNPs were evenly dispersed in the coated PLGA sheet. Cellular experiments revealed that these encapsulated AuNP-antagomiR204 were able to be released from the PLGA sheet and uptaken by adherent BMSCs. In vivo animal study further confirmed that the AuNP-antagomiR204 released from PLGA sheet promoted osseointegration, as revealed by microcomputerized tomography (microCT) reconstruction and histological assay. Taken together, this study established that miR204 misexpression accounted for the deficient osseointegation in diabetes mellitus, while PLGA sheets aided the release of AuNP-antagomiR204, which would be a promising strategy for titanium implant surface functionalization toward better osseointegration.