Effect of mechanical forces on the behavior of osteoblasts: a systematic review of in vitro studies.

Mechanical loading can play a critical role in bone modeling/remodeling through osteoblasts, with several factors being involved in this process.The present study aims to systematically review the effect of mechanical stimulation on human osteoblast cell lineage combined with other variables.The PubMed and Scopus databases were electronically searched for studies analyzing the effect of compression and tension on human osteoblasts at different differentiation stages. Studies that used carcinogenic osteoblasts were excluded. In addition, studies that did not analyze the osteogenic differentiation or proliferation of cells were excluded. The risk of bias of the studies was evaluated using the modified CONSORT (Consolidated Standards of Reporting Trials) checklist. a total of 20 studies were included. The cells were subjected to tension and compression in 5 and 15 studies, respectively. The application of uniaxial and cyclic strain increased the proliferation of osteoblasts. The same increased pattern could be observed for the osteogenesis of the cells. The impact of the tensile force on the expression of the osteoclastic markers differed based on the loading characteristics. On the other side, the impact of compression on the proliferation of osteoblasts varied according to the magnitude and duration of the force. Besides, different patterns of alternations were observed among the osteogenic markers in response to compression. Meanwhile, compression increased the expression of the osteoclastic markers. It has been shown that the response of the markers related to bone formation or resorption can be altered based on the differentiation stage of the cells, the cell culture system, and the magnitude and duration of the force.

Application of chemical factors for acceleration of consolidation phase of the distraction osteogenesis: a scoping review.

PURPOSE: This study aimed to analyze the effect of injecting chemical factors compared to conventional distraction osteogenesis (DO) treatment on the bone formation of the distracted area of the maxillofacial region in human and animal studies. METHOD: Electronic search was done in PubMed, Scopus, Embase, and Cochrane database for studies published until September 2021. The studies' risk of bias (ROB) was assessed using the Cochrane Collaborations and NIH quality assessment tools. Meta-analyses were performed to assess the difference in the amount of bone formation and maximal load tolerance. RESULTS: Among a total of 58 included studies, eight studies analyzed the bone formation rate of the distracted area in human models and others in animal models. Results of the human studies showed acceptable outcomes in the case of using bone morphogenic protein-2 (BMP-2), autologous bone-platelet gel, and calcium sulfate. However, using platelet reach plasma does not increase the rate of bone formation significantly. Quantitative analyses showed that both BMP-2 (SMD = 26.57; 95% CI = 18.86 to 34.28) and neuron growth factor (NGF) (SMD = 16.19; 95% CI = 9.64 to 22.75) increase the amount of bone formation. Besides, NGF increased the amount of load tolerance significantly (SMD = 30.03; 95% CI = 19.91 to 40.16). Additionally, BMP-2 has no significant impact on the post-treatment maxillary length (SMD = 9.19; 95% CI = - 2.35 to 20.73). CONCLUSION: Limited number of human studies with low quality used chemical factors to enhance osteogenesis and showed acceptable results. However, more studies with higher quality are required.

Comparison of Periodontal Ligament Stem Cells with Mesenchymal Stem Cells from Other Sources: A Scoping Systematic Review of In vitro and In vivo Studies.

OBJECTIVE: The application of stem cells in regenerative medicine depends on their biological properties. This scoping review aimed to compare the features of periodontal ligament stem cells (PDLSSCs) with stem cells derived from other sources. DESIGN: An electronic search in PubMed/Medline, Embase, Scopus, Google Scholar and Science Direct was conducted to identify in vitro and in vivo studies limited to English language. RESULTS: Overall, 65 articles were included. Most comparisons were made between bone marrow stem cells (BMSCs) and PDLSCs. BMSCs were found to have lower proliferation and higher osteogenesis potential in vitro and in vivo than PDLSCs; on the contrary, dental follicle stem cells and umbilical cord mesenchymal stem cells (UCMSCs) had a higher proliferative ability and lower osteogenesis than PDLSCs. Moreover, UCMSCs exhibited a higher apoptotic rate, hTERT expression, and relative telomerase length. The immunomodulatory function of adipose-derived stem cells and BMSCs was comparable to PDLSCs. Gingival mesenchymal stem cells showed less sensitivity to long-term culture. Both pure and mixed gingival cells had lower osteogenic ability compared to PDLSCs. Comparison of dental pulp stem cells (DPSCs) with PDLSCs regarding proliferation rate, osteo/adipogenesis, and immunomodulatory properties was contradictory; however, in vivo bone formation of DPSCs seemed to be lower than PDLSCs. CONCLUSION: In light of the performed comparative studies, PDLSCs showed comparable results to stem cells derived from other sources; however, further in vivo studies are needed to determine the actual pros and cons of stem cells in comparison to each other.

Efficacy of Regenerative Medicine for Alveolar Cleft Reconstruction: A Systematic Review and Meta-analysis.

OBJECTIVE: The objective of this study is to analyze the efficacy and complications of regenerative medicine compared to autogenous bone graft for alveolar cleft reconstruction. METHOD: Electronic search was done through PubMed, Scopus, Embase and Cochrane databases for the studies published until May 2021. No limitations were considered for the type of the included studies. The risk of bias (ROB) of the studies was assessed using the Cochrane Collaborations and NIH quality assessment tool. Meta-analyses were performed to assess the difference in the amount of bone formation and rate of complications. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used for analyzing the level of the evidence. RESULTS: Among a total of 42 included studies, 21 studies used growth factors, 16 studies delivered cells, and five studies used biomaterials for bone regeneration of the alveolar cleft. Results showed no significant difference in the amount of bone formation between bone morphogenic protein-2 and iliac graft treated patients after six months (P = 0.44) and 12 months (P = 0.17) follow-up. Besides, higher swelling (OR=9.46, P < 0.01) and less infection (OR=0.19, P = 0.01) were observed in BMP treated patients. Using stem cells can reduce the post-treatment pain (OR=0.04, P = 0.01), but it has no significant impact on other complications (P > 0.05). Using tissue engineering methods reduced the operation time (SD=1.06, P < 0.01). GRADE assessment showed that results regarding the amount of bone formation volume after six and 12 months have low level of evidence. CONCLUSION: Tissue engineering methods can provide a comparable amount of bone formation to the autogenous graft and reduce some of the complications, operation time and hospitalization duration.

Effect of metformin on the behavior of dental pulp stem cells cultured on freeze-dried bone allografts.

BACKGROUND: Considering the complications associated with autogenous bone grafting, the use of freezedried bone allograft (FDBA) granules may be considered as an alternative treatment plan. OBJECTIVES: The aim of this study was to evaluate the effect of metformin on both the proliferation and osteogenic capability of dental pulp stem cells (DPSCs) cultured on FDBA granules. MATERIAL AND METHODS: First, a pilot study was conducted only on DPSCs to confirm cellular viability and the osteoinducing effect of 100 µmol/L metformin. Next, the cells were loaded on FDBA granules and treated with and without metformin. Finally, the following analyses were performed: scanning electron microscopy (SEM) (cell attachment); the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (proliferation); and alkaline phosphatase (ALP) activity analysis (osteogenic differentiation). RESULTS: The SEM images revealed that metformin enhanced the adhesion of DPSCs on FDBA granules. In addition, metformin was shown to increase cell proliferation/viability from day 1 to day 7. Compared to the control, a significant difference was observed after 7 days of treatment. Metformin enhanced the osteogenic capability of FDBA in both standard and osteoinducing conditions. An increase in ALP activity was significant after 7 days of treatment. The positive effect of metformin on differentiation was significant in osteoinducing conditions. CONCLUSIONS: Metformin can be applied as an additional osteoinductive factor in bone regeneration treatment. Moreover, scaffolds with controlled release of metformin can be considered a proper osteoinductive bone substitute that may lessen the complications related to applying allograft scaffolds alone.

The effect of single/multiple micro-osteoperforation on the rate of orthodontic tooth movement and its possible complications: A systematic review and meta-analysis.

OBJECTIVE: Different surgical and non-surgical approaches have been proposed to accelerate tooth movement and decrease the duration of orthodontic treatments. Recently, less invasive techniques such as micro-osteoperforation (MOP) are becoming more common. Several clinical trials have been performed to analyse the effect of MOP. This systematic review with meta-analyses was done to evaluate the effect of MOP on the rate of orthodontic tooth movement (OTM) and its complications. MATERIAL AND METHODS: Electronic search was done in PubMed and Cochrane database for studies published until January 2021. Comparative randomized clinical trial studies with 10 or more participants per group were included. The risk of bias (ROB) of the studies was assessed according to the Cochrane Collaborations tool. Meta-analyses were performed to assess the mean difference in tooth movement rate and compare the level of pain between MOP and control groups. RESULTS: Among a total of 15 included studies, eight studies were at low ROB, while others had unclear ROB. Ten studies evaluated the effect of MOP on OTM rate in canine retraction, and related meta-analysis showed a significant difference between the MOP and control group [SMD=0.42; 95% CI=0.20 to 0.63, P<0.01]. Besides, quantitative analysis showed MOP caused no significant higher anchorage loss [SMD=0.01; 95% CI=-0.15 to 0.13, P=0.89] and pain [SMD=0.54; 95% CI=-0.25 to 1.33, P=0.18]. CONCLUSIONS: Overall, both single and multiple applications of MOP increased the rate of OTM. However, the meta-analysis results of the four studies with low risk of bias showed that there is no significant difference in the rate of tooth movement between MOP and control groups. Besides, it has been shown that MOP did not significantly increase the level of pain, anchorage loss, and periodontal complications.

Comparison of 0.2% chlorhexidine mouthwash with and without anti-discoloration system in patients with chronic periodontitis: A randomized controlled clinical trial.

Background: Chemical plaque control, an adjunct to mechanical approaches, could improve the maintenance of patients with different types of periodontitis. Chlorhexidine, the gold standard in chemical plaque control, might have some side effects; the most determining one is tooth discoloration. Anti-discoloration systems (ADS) have been added to minimize brownish tooth discoloration. This study aimed to evaluate the staining potential and clinical efficacy of chlorhexidine with and without ADS in patients with chronic periodontitis. Methods: In this randomized controlled trial, 46 patients with chronic periodontitis were randomly allocated to two groups. Each patient used 10 mL of mouthwash A (CHX without ADS) or B (CHX with ADS, including sodium metabisulfite and ascorbic acid) twice a day for two weeks. After a two-week interval, they used the second mouthwash. At the beginning and the end of each two-week cycle, plaque index (PI), bleeding on probing (BoP), and staining index were recorded. Results: There was no significant difference between mouthwash A and B in the reduction of BoP and PI. The staining index was significantly lower after rinsing with mouthwash B compared to mouthwash A. Conclusion: CHX mouthwash containing ADS has similar efficacy in microbial plaque control and reduction of BOP as CHX without ADS, with the advantage of lower stain formation on tooth surfaces in patients with chronic periodontitis.

Allogenic vs. synthetic granules for bone tissue engineering: an in vitro study.

The aim of this study was to compare human dental pulp stem cells' (DPSCs) attachment, proliferation and osteogenic differentiation on allogenic and synthetic biphasic bone granules. In this in vitro study, two types of bone granules were used: allograft [freeze-dried bone allograft (FDBA)] and biphasic granules [hydroxyapatite/beta-tricalcium phosphate (HA/ß-TCP)]. By isolation of DPSCs, their attachment to bone granules was observed by scanning electron microscope (SEM) at day 1 and 7 of cultivation. Vital cells were measured by MTT assay at 1, 3, and 7 days of cell culture. Comparison of vital cells at different time points was considered as cell proliferation. Finally, differentiation of DPSCs was evaluated by measurement of alkaline phosphatase (ALP) activity 3, 7, 14, and 21 days after cell seeding in standard and osteogenic media. Data were analyzed using two-way ANOVA with a significant level of 0.05. Attachment of DPSCs on FDBA granules seemed relatively stronger. The number of cells (based on MTT values) and ALP activity of the cells cultured on both study groups increased between time points (p ≤ 0.001). FDBA granules had more cells compared to HA/ß-TCP granules (p < 0.001). There was no significant difference between ALP activity of two study groups cultured in the standard medium (p = 0.347) and they were both higher than the control group (p < 0.05). In the osteogenic medium, FDBA group had significantly higher ALP activity compared to HA/ß-TCP (p = 0.035) and control (p = 0.001) groups while there was no significant difference between ALP activity of HA/ß-TCP and control groups (p = 0.645). In conclusion, current in vitro study revealed that FDBA granules have more potential in supporting DPSCs attachment and proliferation and inducing their ALP activity compared to HA/ß-TCP granules. Therefore, FDBA could serve as a proper bone substitute material.

Effect of metformin on dental pulp stem cells attachment, proliferation and differentiation cultured on biphasic bone substitutes.

OBJECTIVE: To evaluate to the effect of metformin on attachment of human dental pulp stem cells (hDPSCs) and their proliferation and osteogenic differentiation on biphasic hydroxyapatite/beta-tricalcium phosphate granules of macro-porous biphasic calcium phosphate (MBCP). MATERIALS AND METHODS: This in vitro study included four groups: A:hDPSCs + MBCP + Metfromin, B:hDPSCs + MBCP, C:hDPSCs + Metformin and D:hDPSCs (control). Attachment of hDPSCs to bone granules in groups A and B was observed by scanning electron microscopy on days 1 and 7 of cultivation. Cell viability was assessed by MTT assay on days 1, 3, and 7 after cell seeding. Differentiation of the hDPSCs was assessed by measurement of alkaline phosphatase activity on days 3, 7, 14 and 21 after cell culturing in standard and osteogenic media. The data was analyzed by two-way ANOVA at a significance level of p = 0.05. RESULTS: The hDPSCs had firmly attached to the surface of MBCP granules, especially in group A. The MTT values increased in all groups from day 1 to day 7 (p < 0.001). The highest MTT values were observed in group C followed by the control group and groups A and B (p < 0.001). Alkaline phosphatase activity also increased in all groups between days 3 to 21 (p < 0.001) except between days 7 and 14 in standard media (p = 0.094). In standard media, groups with MBCP granules (A and B) showed higher activity (p < 0.05). In osteogenic media, the groups with metformin (A and C) showed higher alkaline phosphatase activity (p < 0.05). CONCLUSION: This in vitro study showed that 100 Mol/L metformin increased attachment and proliferation of hDPSCs on biphasic granules. Osteogenic differentiation of hDPSCs also increased in the presence of metformin.

Failure Rate of Pediatric Dental Treatment under General Anesthesia.

Aim: To assess the failure rates of various pediatric dental treatments performed under general anesthesia (GA) after six months to five years of follow-up. Design: This multicenter retrospective cohort study was performed on patients treated by five pedodontists in two private hospitals located in northern Iran during 2010⁻2013 and comprised 155 patients. The patients were recalled and clinically examined. During the clinical examination of the primary teeth, oral hygiene, dmft index, and failure of previous treatments was evaluated. The data were analyzed using the Chi square and regression analyses with a significance level of 0.05. Results: 114 patients (74 males and 40 females, mean age: 37.17 ± 10.75 months) with 1155 primary teeth treated under GA participated in the follow-up. The overall failure rate was 6.59%. The failure rates of pulpectomy, pulopotomy, fissure sealant, stainless steel crown (SSC), amalgam, and composite fillings were 2.90%, 3.03%, 4.83%, 5.26%, 5.33%, and 9.63%, respectively. Among the confounding factors, only gender had a significant effect on the anterior composite failure rate (p = 0.029) and age had a significant effect on the failure rate of fissure sealant therapy (p = 0.015) and SSC (p = 0.018). Conclusion: The overall rate of treatment failure in pediatric patients, treated under GA, was 6.59%.

Detection of Hepatitis C Virus RNA in Blood and Saliva of Transfusion-Dependent Thalassemia Patients Diagnosed with Hepatitis C.

BACKGROUND: The aim of the current study was to detect hepatitis C virus (HCV) RNA in blood and saliva of a population of patients with thalassemia who have HCV antibody in their serum. MATERIALS AND METHODS: In this cross-sectional study, blood and saliva samples were collected and were analyzed with quantitative reverse transcription polymerase chain reaction (RT-PCR) for the detection of HCV RNA. In addition, liver-related blood tests were performed, and patients' medical history was recorded. Data were analyzed by independent samples t-test and Chi-square with a significant level of 0.05. RESULTS: Overall, 62 adult patients (29 males and 33 females) were included. Most (87%) of the patients had major thalassemia and genotype 1a was the most common (42%) type. HCV RNA was detected in 71 and 16% of blood and saliva samples, respectively. HCV RNA was detected more in female patients (31%) (P = 0.003) and in intermediate thalassemia (50%) (P < 0.005). The mean age of the patients with positive saliva was almost 10 years older (P < 0.001), and the mean number of blood transfusion was fewer in positive saliva group (P = 0.037). The sensitivity, specificity, and positive and negative predictive values of saliva PCR was calculated to be 18%, 88%, 80%, and 69%, respectively. CONCLUSION: Saliva contained HCV RNA in 16% of the assessed population. The probability of detection of HCV RNA in saliva increased in older patients, less number of blood transfusions, females and intermediate thalassemia. Saliva RT-PCR demonstrated low sensitivity and high specificity with high positive predictive value in the assessed population.