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Wound healing in the oral mucosa is superior to that in the skin, with faster wound closure accompanied by reduced inflammation, less angiogenesis, and minimal scar formation. A well-characterized oral wound model is critical to investigating the mechanisms of oral wound closure and the efficacy of various clinical interventions. Currently, there are a few human oral wound models, although none of them are well characterized. In the present study, we describe and characterize a human hard palate wound healing model. A 3.5-mm circular and two 1 × 5-mm rectangular full-thickness wounds were made in the first and second molar region, 5 mm from the gingival margin, on the hard palate of human subjects. The circular wound was used to monitor wound closure and collect swabs for a microbiome analysis via 16s rRNA sequencing. The rectangular wounds were biopsied and the tissue was used to evaluate the gene expression of wound healing-related mediators by real-time polymerase chain reaction. Saliva was also collected to examine the protein levels of similar molecules by enzyme-linked immunosorbent assays. Circular wounds were nearly closed on day 7 after wounding. Significant changes in the gene expression of inflammatory cytokines, growth factors, antimicrobial peptides, and extracellular matrix-related molecules were identified in day 1 and day 3 wound tissue and compared with unwounded tissue on day 0. Changes in the protein levels of various mediators were limited in the saliva. In addition, alpha diversity, beta diversity, and differential microbiome analysis demonstrated significant changes in bacterial colonization of the wound surface over time compared with unwounded mucosa. In summary, we comprehensively characterize a human hard palate wound-healing model that details the dynamic changes of wound closure, levels of wound healing-related mediators in the wound and saliva, and the oral wound microbiome. [ABSTRACT FROM AUTHOR]

This study aimed to clinically evaluate the accuracy of Dental Monitoring's (DM) artificial intelligence (AI) image analysis and oral hygiene notification algorithm in identifying oral hygiene and mucogingival conditions. Twenty-four patients seeking orthodontic therapy were monitored by DM oral hygiene protocol during their orthodontic treatment. During the bonding appointment and at each of 10 subsequent adjustment visits, a total of 232 clinical oral examinations were performed to assess the presence of the 3 oral hygiene parameters that DM monitors. In each clinical timepoint, the subjects took an oral DM scan and received a notification regarding their current oral status at that moment in time. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated to evaluate AI and clinical assessment of plaque, gingivitis, and recession. A total of 232 clinical time points have been evaluated clinically and by the DM AI algorithm. For DM's AI detection of plaque and calculus, gingivitis, and recession, the sensitivity was 0.53, 0.35, and 0.22; the specificity was 0.94, 0.96, and 0.99; and the accuracy was 0.60, 0.49, and 0.72, respectively. DM's oral hygiene notification algorithm has low sensitivity, high specificity, and moderate accuracy. This indicates a tendency of DM to underreport the presence of plaque, gingivitis, and recession. • Dental Monitoring's (DM) oral hygiene notification algorithm has low sensitivity. • The DM algorithm also exhibits high specificity and moderate accuracy. • There is a tendency of DM to underreport the presence of plaque, gingivitis, and recession. [ABSTRACT FROM AUTHOR]

An in-vivo evaluation of the Dental Monitoring (DM; Paris, France) Artificial Intelligence Driven Remote Monitoring technology was conducted in an active clinical setting. Our objectives were to compare the accuracy and validity of the 3-dimensional (3D) digital models remotely generated from the DM application to 3D Digital Models generated from the iTero Element 5D intraoral scanner (Align Technologies, San Jose, Calif) of patients' dentition during in-vivo fixed orthodontic treatment. The orthodontic treatment of 24 patients (aged 14-55 years) was tracked across an average of 13.4 months. Scans of the maxillary and mandibular arches of each patient were taken by an iTero intraoral scanner and with the DM application before treatment initiation without (T 0) and with (T 1) the fixed orthodontic appliances and at every in-person adjustment appointment (T 2 -T 10). The global deviation between the reconstructed digital models from the DM and iTero scans was compared at each time point using Geomagic Control-X 2020 (3D Systems, Rock Hill, SC). Descriptive analysis was conducted to determine the mean deviation at each time point for the maxillary and mandibular arches, to compare the maxilla and mandible mean deviations at each time point to the null hypothesis mean of 0 mm and the paired mean of the average at each time point between the maxilla and mandible. The findings revealed no clinically significant difference between the reconstructed digital models generated by the iTero IOS and the remotely reconstructed digital dental models generated by the DM application. DM artificial intelligence tracking algorithm can track tooth movement and reconstruct 3D digital models to a clinically acceptable degree for orthodontic application. • An in-vivo evaluation of AI driven remote monitoring technology. • Remote tracking of orthodontics tooth movement by AI. • Remote Reconstruction of 3D Models by AI. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cell (MSC) derived extracellular vesicles (EVs) in their naïve and engineered forms have emerged as potential alternatives to stem cell therapy. While they have a defined therapeutic potential, the spatial and temporal control of their activity in vivo remains a challenge. The objective of this study was to devise a methodology to encapsulate EVs in 3D hydrogels for prolonged delivery. To achieve this, we have leveraged the MSC EV interactions with ECM proteins and their derivative peptides. Using osteoinductive functionally engineered EVs (FEEs) derived from MSCs, we show that FEEs bind to mimetic peptides from collagen (DGEA, GFPGER) and fibronectin (RGD). In in vitro experiments, photocrosslinkable alginate hydrogels containing RGD were able to encapsulate, tether and retain the FEEs over a period of 7 days while maintaining the structural integrity and osteoinductive functionality of the EVs. When employed in a calvarial defect model in vivo , alginate-RGD hydrogels containing the FEEs enhanced bone regeneration by a factor of 4 compared to controls lacking FEEs and by a factor of 2 compared to controls lacking the tethering peptide. These results show that EVs can be tethered to biomaterials to promote bone repair and the importance of prolonged delivery in vivo. Results also provide a prelude to the possible use of this technology for controlled delivery of EVs for other regenerative medicine applications. The beneficial effects of human MSC (HMSC) therapy are attributable to paracrine effects of the HMSC derived EVs. While EV engineering has the potential to impact several fields of regenerative medicine, targeted delivery of the engineered EVs with spatial and temporal control is necessary to prevent off-target effects and enhance tissue specificity. Here, we have leveraged the interactions of MSC EVs with ECM proteins to develop a tethering system that can be utilized to prolong EV delivery in vivo while maintaining the structural and functional integrity of the EVs. Our work has provided a tunable platform for EV delivery that we envision can be formulated as an injectable material or a bulk hydrogel suitable for regenerative medicine applications. [Display omitted] [ABSTRACT FROM AUTHOR]

Lineage specific differentiation of host mesenchymal stem cells (MSCs) is a necessary step for bone repair/regeneration. Clinically, growth factors such as bone morphogenetic protein 2 (BMP2) are used to enhance/hasten this process to heal critical sized defects. However, the clinical application of such growth factors is fraught with dosage challenges as well as immunological and ectopic complications. The identification of extracellular vesicles (EVs) as active components of the MSC secretome suggest alternative approaches to enhancing bone regeneration. Based on our earlier studies on the properties of EVs from lineage specified MSCs, this study sought to engineer EVs to enhance osteogenic differentiation. To generate MSC EVs with enhanced osteoinductive abilities, genetically modified human bone marrow derived MSCs (HMSCs) were generated by constitutively expressing BMP2. We hypothesized that these cells would generate functionally engineered EVs (FEEs) with enhanced osteoinductive properties. Our results show that these FEEs maintained the general physical and biochemical characteristics of naïve HMSC EVs in the form of size distribution, EV marker expression and endocytic properties but show increased bone regenerative potential compared to MSC EVs in a rat calvarial defect model in vivo. Mechanistic studies revealed that although BMP2 was constitutively expressed in the parental cells, the corresponding EVs (FEEs) do not contain BMP2 protein as an EV constituent. Further investigations revealed that the FEEs potentiate the BMP2 signaling cascade possibly due to an altered miRNA composition. Collectively, these studies indicate that EVs' functionality may be engineered by genetic modification of the parental MSCs to induce osteoinduction and bone regeneration. With mounting evidence for the potential of MSC EVs in treatment of diseases and regeneration of tissues, it is imperative to evaluate if they can be modified for application specificity. The results presented here indicate the possibility for generating Functionally Engineered EVs (FEEs) from MSC sources. As a proof of concept approach, we have shown that EVs derived from genetically modified MSCs (BMP2 overexpression) can be effective as biomimetic substitutes for growth factors for enhanced tissue-specific regeneration (bone regeneration) in vivo. Mechanistic studies highlight the role of EV miRNAs in inducing pathway-specific changes. We believe that this study will be useful to researchers evaluating EVs for regenerative medicine applications. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to test a hypothesized positive association between low vitamin D (VitD) serum levels and the severity of periodontal disease in women with HIV infection.Study Design: This was a cross-sectional secondary analysis of data from an oral substudy conducted within the Chicago site of the Women's Interagency HIV Study. Serum VitD levels and clinical attachment loss (CAL) measurements were available for 74 women with HIV infection. VitD levels were treated as both continuous and categorical variables in bivariate and multivariate analyses. Mean clinical attachment loss (mCAL) was determined for each subject by obtaining the averages of measurements taken at 4 sites in each measured tooth.Results: Average age of study participants (n = 74) was 39.6 years (standard deviation 7.2), and the majority were African Americans (70.3%) with VitD deficiency (58.1%). VitD deficiency was positively associated with higher mCAL (P = .012). After adjustment for race, age, smoking, and HIV viral load, an association was found between VitD deficiency and mCAL (Beta 0.438; P = .036).Conclusions: We identified a previously unreported association between VitD deficiency and mCAL in women with HIV infection. Larger and more inclusive, multisite, longitudinal studies are warranted to investigate whether these findings can be generalized to all individuals with HIV infection in the current treatment era and to determine causality. [ABSTRACT FROM AUTHOR]

Objective The objective of this assessment is to evaluate the degree of risk of bias in randomized controlled trials published in 2013 and focusing on periodontal regeneration. Methods Three reviewers searched and selected the trials based on pre-defined inclusion criteria. Predictor variables [number of authors, primary objective of the study, biomaterial employed, follow-up time periods, split mouth study (yes/no), journal, year of publication, country, scale (single/multi-center) and nature of funding] were extracted and risk of bias assessment using Cochrane risk of bias tool were performed independently by the three reviewers. Results Seventeen RCTs were included in this assessment. The risk of bias in RCTs published in 2013 with a focus in periodontal regeneration varied significantly with only in less than 30% of the included trials, the overall risk of bias was found to be low, while 41% of trials were designated to have a higher degree of bias. Specifically, when looking at the domains assessed, 70% of the included trials reported an accepted method of sequence generation, blinding (whenever possible), completeness of outcome data or avoided selective outcome reporting. Meanwhile, only 47% of the included trials reported some form of allocation concealment. Conclusion In this assessment, of the included 17 trials, slightly more than 40% of them had a high risk of bias, underscoring the importance of careful appraisal of trials before implementing the study interventions in clinical practice and the need for more detailed analyses. [ABSTRACT FROM AUTHOR]

Objective Clinical trials serve as the empirical basis for clinical decision making. The objective of the current study is to provide an overview of clinical trials examining dental implant outcomes. Method All registered studies on Dental Implants were selected for analysis. The clinicaltrials.gov website was used to query the characteristics of registered studies. The search term used was dental implants. Results As of the study conduct date (01/01/2014), a total of 205 studies on dental implants were registered. These included 168 interventional and 37 observational studies. Results were available for only 14 studies. All observational studies and 98.8% of interventional studies included both male and female subjects. Close to 60% of studies had sample sizes between 1 and 50. NIH was listed as funding source in only 5 interventional studies and 3 observational studies. 80% of interventional studies were randomized. However, double masking was reported in only 15% of interventional studies with majority being open labeled. Conclusion ClinicalTrials.gov registry was created with the intention of increasing the transparency of conducted or ongoing clinical studies and to minimize publication bias commonly seen with industry-sponsored studies. Results of the current study showed that a predominating number of registered studies are funded by industry and other sources, very few registered studies have made their results public, and the ClinicalTrials.gov registry does not provide sufficient information on the quality of study design and thus precluding the public and researchers to judge on the quality of registered studies and publication bias. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to provide estimates of hospitalizations attributed to oral health related conditions in the United States (US). Study Design: The nationwide inpatient sample (NIS) of the Healthcare Cost and Utilization Project (HCUP) for 2008 was used. Hospital admissions with a primary diagnosis of dental/oral health–related conditions were identified using ICD-9-CM diagnosis codes. Results: A total of 50,658 hospital admissions were primarily attributed to oral health–related conditions in 2008. Total US hospitalization charges were $1.218 billion. Total US hospitalization days were 174,496 days. Conclusions: The current study examines outcomes in patients hospitalized primarily for dental/oral health–related conditions. Of 39,885,120 hospitalizations that occurred in the US, a total of 50,658 (1.27%) were primarily attributed to dental-related conditions. Substantial resources are spent in treating dental-related conditions in hospital settings. [Copyright &y& Elsevier]

Despite accelerated epithelial closure, oral mucosal wounds exhibit lower levels of VEGF and a more refined angiogenic response than do skin wounds. The specific differences in angiogenesis suggest that skin and oral mucosal wounds may experience dissimilar levels of hypoxia and HIF-1α. Using a model of comparable wounds on murine dorsal skin and tongue, we determined levels of hypoxia and HIF-1α. Skin wounds were found to be significantly more hypoxic and had higher levels of HIF-1α than mucosal wounds. Furthermore, under stressed conditions, skin wounds, but not mucosal wounds, exhibited a further elevation of HIF-1α beyond that of non-stressed levels. To determine if manipulation of oxygen levels might equalize the repair response of each tissue, we exposed mice to hyperbaric oxygen treatment (HBOT) following wounding. HBOT did not significantly change HIF-1α or VEGF expression in either skin or mucosal wounds, nor did it alter wound bed vascularity. These studies suggest that skin wounds have higher levels of hypoxia than do mucosal wounds, along with a differential expression of HIF-1α. Interestingly, modulation of oxygen by HBOT does not ameliorate this difference. These results suggest that differential responses to hypoxia may underlie the distinctive wound-healing phenotypes seen in skin and oral mucosa. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study is to provide nationally representative estimates of cleft palate correction and revision procedures performed in hospitalized patients, as well as to examine patient- and hospital-level factors associated with hospitalization charges. Materials and Methods: The Nationwide Inpatient Sample for the year 2007 was used. All hospitalizations that had a cleft palate correction or revision of cleft palate repair were selected. Estimates of concomitant procedures performed during the index hospitalization were obtained. The roles of different patient- and hospital-level variables on hospitalization charges were examined by use of multivariable linear regression analysis. Results: A total of 5,969 repairs and/or revisions of cleft palate procedures were performed in hospitals in the entire United States. The mean age per hospitalization was 3.2 years. Whites accounted for 51.3% of procedures, whereas blacks, Hispanics, Asian/Pacific Islanders, Native Americans, and other races accounted for 4.9%, 26.4%, 9.2%, 3.2%, and 5%, respectively. The mean charge per each hospitalization was $19,227, and the total hospitalization charge for the entire United States was $112.96 million. Patients aged less than 1 year (P = .02) and those aged between 8 and 12 years (P = .03) had significantly lower charges compared with those aged 18 years or older. Use of bone morphogenetic protein was associated with higher hospital charges (P = .0006). Compared with the uninsured, those covered by Medicaid (P = .04), private insurance plans (P = .02), and other insurance plans (P = .0005) were associated with higher charges. Conclusion: This study identified an association between hospital charges and insurance payer, race, treatments performed, and age. Our results provide insights into nationally representative estimates on management of cleft palate corrections and revisions. [Copyright &y& Elsevier]

OBJECTIVE: We studied the association between presence of complications and hospitalization outcomes, including hospital charges, length of stay in hospital, and in-hospital mortality. METHODS: The Nationwide Inpatient Sample for 2008 was used. All hospital discharges with a primary diagnosis of oral and oropharyngeal cancers were selected. Presence of complications was determined by using ICD-9-CM codes. The association between the presence of complications and outcomes (hospital charges, length of stay, and in-hospital mortality) was examined by multivariable linear and multivariable logistic regression analyses. The effects of several patient- and hospital-related confounders were adjusted in the regression analyses. RESULTS: A total of 17,632 hospitalizations were attributed to oral and oropharyngeal cancers. A total of 519 (2.9%) patients died in the hospitals. The total hospitalization charges were close to $1.08 billion. Oral and oropharyngeal cancers accounted for 117,472 hospitalization days (mean length of stay 6.6 days). The overall complication rate was 14.95%. The most frequently present complication was hemorrhagic complications. Among the different complications, septicemia was associated with the worst outcomes. Patients with septicemia were associated with the highest odds for in-hospital mortality (OR = 13.06, 95% CI = 3.81-48.50, P = .0001). CONCLUSIONS: Presence of complications was associated with poor outcomes, such as high in-hospital mortality rates, excess hospitalization charges, and longer length of stay in hospital. Among the different complications, septicemia was associated with the worst outcomes. [ABSTRACT FROM AUTHOR]

The article presents information related to periodontal diseases. It offers information on the definition, epidemiology, etiology, pathogenesis, symptoms, diagnosis, classification and treatment of the disease. It covers diseases in children including Down syndrome, leukocyte adhesion deficiency and neutropenia. It discusses the role of periodontitis in pregnancy.

Abstract: Background: Relatively localized conditions such as infection of the pulp or periapical tissues if left untreated could spread and require hospital care. The objectives of this study were to assess the prevalence of such hospital-based emergency department (ED) visits, to quantify hospital charges associated with those visits, and to identify characteristics of those members of the population who are likely to make such visits. Methods: The experimental design of this study involves the use of The Nationwide Emergency Department Sample for the year 2006. All discharges with a primary diagnosis code for pulpal and periapical diseases (International Classification of Disease, Clinical Modification [ICD-9-CM] code of 522) were selected for analysis. All estimates were projected to national levels using the discharge weight variables. Results: In the United States, during the year 2006, a total of 403,149 ED visits had a primary diagnosis code for pulp and periapical diseases. The average patient age was 32.9 years. The mean hospital charge for ED visits was $480, and the total charges for all the ED visits in the United States was $163,692,957. Among the ED visits, 5,721 were admitted to the same hospital for inpatient care. The mean length of stay after hospitalization was 2.95 days. The uninsured (39.92%) constituted the largest proportion of all ED visits. Conclusions: This study identifies high-risk groups that are likely to present to hospital-based EDs for the treatment of pulp and periapical diseases. This highlights the need for significant resources to treat such patients in a hospital care setting. [ABSTRACT FROM AUTHOR]

Background: Cybersecurity threats are a growing concern in healthcare, where digital systems now underpin patient care, financial management, and educational operations. A cybersecurity breach in a Dental school environment can have widespread consequences to the mission of the school-patient care, research, education and service. For dental school administrators, these risks highlight the necessity of robust cybersecurity measures. For student learners, the impact may include interruptions to their education. For patients, it could mean compromised personal data and reduced access to clinical care., Results & Conclusion: While many sectors have responded to increasing cyber threats by enhancing their defenses, healthcare and dental schools, often lag in implementing necessary protections. This emphasizes the need for proactive measures, such as regular system audits, advanced encryption methods, and ongoing cybersecurity training for administrators and students alike, to mitigate future risks and safeguard institutional integrity., (© 2024 The Author(s). Journal of Dental Education published by Wiley Periodicals LLC on behalf of American Dental Education Association.)

Introduction: Mesenchymal stem cell-derived extracellular vesicles (MSC EVs) hold significant promise for regenerative medicine. Lyophilization of EVs significantly enhances their translational potential. While, lyophilized EVs have been studied from a morphological perspective, the functional stability of these EVs and their cargo following lyophilization need to be mechanistically investigated., Methods: In this study, we investigated the functional and mechanistic bioactivity of fresh versus lyophilized MSC EVs, specifically focusing on functionally engineered osteoinductive EVs developed in our laboratory. We utilized dimethyl sulfoxide (DMSO) as a cryoprotectant and conducted pathway-specific in vitro and in vivo experiments to assess the stability and functionality of the EVs., Results: Our findings show that using DMSO as a cryoprotectant before lyophilization preserves the functional stability of engineered MSC EVs. In vitro experiments demonstrated that the endocytosis, cargo integrity, and pathway-specific activity of lyophilized EVs were maintained when DMSO was used as the cryoprotectant. Additionally, in vivo bone regeneration studies revealed that the functionality of cryoprotected lyophilized EVs was comparable to that of freshly isolated EVs., Discussion: These results provide a foundation for evaluating the functionality of lyophilized EVs and exploring the use of DMSO and other cryoprotectants in EV-based therapies. Understanding the functionality of lyophilized naïve and engineered EVs from a mechanistic perspective may enhance validation approaches for tissue regeneration strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Huang, Kang, Debnath, Leung, Raghavan, Lu, Cooper, Gajendrareddy and Ravindran.)

Mesenchymal stem cell derived extracellular vesicles (MSC EVs) are paracrine modulators of macrophage function. Scientific research has primarily focused on the immunomodulatory and regenerative properties MSC EVs derived from bone marrow. The dental pulp is also a source for MSCs, and their anatomical location and evolutionary function has primed them to be potent immunomodulators. In this study, we demonstrate that extracellular vesicles derived from dental pulp stem cells (DPSC EVs) have pronounced immunomodulatory effect on primary macrophages by regulating the NFκb pathway. Notably, the anti-inflammatory activity of DPSC-EVs is enhanced following exposure to an inflammatory stimulus (LPS). These inhibitory effects were also observed in vivo . Sequencing of the naïve and LPS preconditioned DPSC-EVs and comparison with our published results from marrow MSC EVs revealed that Naïve and LPS preconditioned DPSC-EVs are enriched with anti-inflammatory miRNAs, particularly miR-320a-3p, which appears to be unique to DPSC-EVs and regulates the NFκb pathway. Overall, our findings highlight the immunomodulatory properties of DPSC-EVs and provide vital clues that can stimulate future research into miRNA-based EV engineering as well as therapeutic approaches to inflammation control and disease treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Umar, Debnath, Leung, Huang, Lu, Gajendrareddy and Ravindran.)

Purpose: To investigate bone regeneration among three different bone graft materials in a rat calvarum model., Materials and Methods: A total of 24 rats had two 5-mm defects placed per calvarial. Rats were divided into four groups: bovine xenograft (XG), demineralized bone matrix (DBM), mineralized bone graft (MBG), and collagen membrane control (CC). Within each group, samples were collected at two time points: 4 weeks (T4) and 8 weeks (T8). Bone regeneration was assessed by microcomputed tomography (micro-CT) imaging and was analyzed using MATLAB software. Additionally, the fixed samples were subsequently demineralized for immunohistochemistry and histomorphometry. Slides were mounted and stained with hematoxylin and eosin (H&E) stain as well as bone morphogenetic protein 2 (BMP-2) and runt-related transcription factor 2 (RUNX2) markers. The numbers of positive cells/area were calculated for each group and analyzed., Results: At 4 weeks, DBM showed low mineral density (7.7%) compared to the control (25.2%), but increased dramatically at 8 weeks (DBM, T8 = 27.6%; CC, T8 = 27.2%). Xenograft material showed an increase in mineral desnity between T4 and T8 (XG, T4 = 25.0%; XG, T8 = 32.3%). MBG remained consistent over the 8-week trial period (MBG, T4 = 30.4%; MBG, T8 = 30.4%). BMP-2 expression was present in cells adherent to all graft materials. RUNX2 expression was also observed in cells adherent to all graft materials, indicating that during the 4- to 8-week healing period, all materials supported osteogenesis., Conclusions: Compared to other materials, the DBM had high osteoinductive properties during the 4- to 8-week time period based on increased mineral content. All materials were associated with immunohistologic evidence of osteogenesis in the rat calvarial defect model.

Objective: This study aimed to evaluate the effectiveness of Dental Monitoring™ (DM™) Artificial Intelligence Driven Remote Monitoring Technology (AIDRM) technology in improving the patient's oral hygiene during orthodontic treatment through AI-based personalized active notifications., Methods: A prospective clinical study was conducted on two groups of orthodontic patients. DM Group: (n = 24) monitored by DM weekly scans and received personalized notifications on the DM smartphone application regarding their oral hygiene status. Control Group (n = 25) not monitored by DM. Both groups were clinically assessed using Plaque Index (OPI) and the Modified Gingival Index (MGI). DM Group was followed for 13 months and the Control Group was followed for 5 months. Student-independent t test and paired t tests were used to investigate the mean differences between study groups and between time points for each group respectively., Results: At all time points, the mean differences indicated that the DM group had lower OPI and MGI values than the control group. The mean value for OPI and MGI were statistically significantly lower in the DM group (OPI = 1.96, MGI = 1.56) than in the control group (OPI = 2.41, MGI = 2.17) after 5 months. A rapid increase in mean OPI and MGI values was found between T0 and T1 for both study groups. A plateau effect for OPI scores appeared to occur from T1 to T5 for both study groups, but the plateau effect seemed to be more pronounced for the DM group than the study group. The MGI values for both study groups also increased dramatically from baseline to T5, however, a plateau effect was not observed., Conclusions: The oral hygiene of orthodontic patients rapidly worsens over the first 3 months and plateaus after about 5 months of treatment. AIDRM by weekly DM scans and personalized active notifications may improve oral hygiene over time in orthodontic patients., (© 2023 The Authors. Orthodontics & Craniofacial Research published by John Wiley & Sons Ltd.)

Mesenchymal stem cell derived extracellular vesicles (MSC EVs) possess excellent immunomodulatory and therapeutic properties. While beneficial, from a translational perspective, extracellular vesicles with consistent functionality and target specificity are required to achieve the goals of precision medicine and tissue engineering. Prior research has identified that the miRNA composition of mesenchymal stem cell derived extracellular vesicles contributes significantly towards extracellular vesicles functionality. In this study, we hypothesized that mesenchymal stem cell derived extracellular vesicle functionality can be rendered pathway-specific using a miRNA-based extracellular vesicles engineering approach. To test this hypothesis, we utilized bone repair as a model system and the BMP2 signaling cascade as the targeted pathway. We engineered mesenchymal stem cell extracellular vesicles to possess increased levels of miR-424, a potentiator of the BMP2 signaling cascade. We evaluated the physical and functional characteristics of these extracellular vesicles and their enhanced ability to trigger the osteogenic differentiation of naïve mesenchymal stem cell in vitro and facilitate bone repair in vivo. Results indicated that the engineered extracellular vesicles retained their extracellular vesicles characteristics and endocytic functionality and demonstrated enhanced osteoinductive function by activating SMAD1/5/8 phosphorylation and mesenchymal stem cell differentiation in vitro and enhanced bone repair in vivo. Furthermore, the inherent immunomodulatory properties of the mesenchymal stem cell derived extracellular vesicles remained unaltered. These results serve as a proof-of-concept for miRNA-based extracellular vesicles engineering approaches for regenerative medicine applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Kang, Leung, Lu, Shirazi, Gajendrareddy and Ravindran.)

Mesenchymal stem cells show remarkable versatility and respond to extracellular and micro environmental cues by altering their phenotype and behavior. In this regard, the MSC's immunomodulatory properties in tissue repair are well documented. The paracrine effects of MSCs in immunomodulation are, in part, attributable to their secreted extracellular vesicles (EVs). When MSCs migrate to the wound bed, they are exposed to a myriad of inflammatory signals. To understand their response to an inflammatory environment from an EV perspective, we sought to evaluate the effects of the inflammatory cytokine TNFα on MSC EV mediated immunomodulation. Our results indicate that while the physical characteristics of the EVs remain unchanged, the TNFα preconditioned MSC EVs possess enhanced immunomodulatory properties. In vitro experiments using polarized (M1 and M2) primary mouse macrophages indicated that the preconditioned MSC EVs suppressed pro-inflammatory (M1) markers such as IL-1β and iNOS and elevated reparatory (M2) markers such as Arg1 and CD206. When evaluated in vivo in a rat calvarial defect model, the TNFα preconditioned MSC EVs reduced inflammation at 1-, 3- and 7-days post wounding resulting in the subsequent enhanced bone formation at 4- and 8-weeks post wounding possibly by modulation of oncostatin M (OSM) expression. An analysis of EV miRNA composition revealed significant changes to anti-inflammatory miRNAs in the preconditioned MSC EVs hinting at a possible role for EV derived miRNA in the enhanced immunomodulatory activity. Overall, these results indicate that MSC exposure to inflammatory signals influence the MSC EV's immunomodulatory function in the context of tissue repair. The specific function of TNFα preconditioned MSC EV miRNAs in immunomodulatory control of bone regeneration merits further investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kang, Huang, Gajendrareddy, Lu, Shirazi, Ravindran and Cooper.)

Periodontal diseases like gingivitis and periodontitis are primarily caused by dental plaque. Several antiplaque and anti-microbial agents have been successfully incorporated into toothpastes and mouthwashes to control plaque biofilms and to prevent and treat gingivitis and periodontitis. The aim of this article was to review recent developments in the antiplaque, anti-gingivitis, and anti-periodontitis properties of some common compounds in toothpastes and mouthwashes by evaluating basic and clinical studies, especially the ones published in the past five years. The common active ingredients in toothpastes and mouthwashes included in this review are chlorhexidine, cetylpyridinium chloride, sodium fluoride, stannous fluoride, stannous chloride, zinc oxide, zinc chloride, and two herbs-licorice and curcumin. We believe this comprehensive review will provide useful up-to-date information for dental care professionals and the general public regarding the major oral care products on the market that are in daily use.

Multiple local and systemic factors including inflammation influence bone regeneration. Several lines of evidence demonstrate that macrophages contribute to the immunological regulation of MSC and osteoblast function during bone regeneration. Recent studies demonstrate that macrophage polarization influences this regulatory process. In this manuscript, we investigated the paracrine functional role of naïve (M0), M1 and M2 polarized macrophage derived EVs in bone repair. Treatment of rat calvaria defects with no EVs, M0 EVs, M1 EVs, or M2 EVs revealed polarization-specific control of bone regeneration by macrophage EVs at 3 and 6 weeks. M0 and M2 EVs promoted repair/regeneration and M1 EVs inhibited bone repair. Pathway-specific studies conducted in cell culture showed that M1 EVs negatively regulated the BMP signaling pathway, specifically BMP2 and BMP9. In parallel, miRNA sequencing studies showed similar miRNA cargo in M0 and M2 EVs and different miRNA cargo in M1 EVs. Functional examination of M1 macrophage EV-enriched miR-155 demonstrated that miR-155 mimic treatment reduced MSC osteogenic differentiation as measured by reduced BMP2, BMP9 and RUNX2 expression when compared to controls. Conversely, treatment of MSCs with the M2 macrophage EV-enriched miR-378a mimic increased MSC osteoinductive gene expression when compared to controls. These functional studies implicate polarized macrophage EV miRNAs in the positive or negative regulation of bone regeneration that was observed in vivo. Overall, the results presented in this study indicate that macrophage polarization influences EV cargo and related EV function in the paracrine regulation of bone regeneration., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In orthopedics and dentistry there is an increasing need for novel biomaterials and clinical strategies to achieve predictable bone regeneration. These novel molecular strategies have the potential to eliminate the limitations of currently available approaches. Specifically, they have the potential to reduce or eliminate the need to harvest autogenous bone, and the overall complexity of the clinical procedures. In this review, emerging tissue engineering strategies that have been, or are currently being, developed based on the current understanding of bone biology, development and wound healing will be discussed. In particular, protein/peptide based approaches, DNA/RNA therapeutics, cell therapy, and the use of exosomes will be briefly covered. The review ends with a summary of the current status of these approaches, their clinical translational potentials and their challenges.

Mesenchymal stem cells (MSCs) are multipotent cells with regenerative and immunomodulatory properties. Several aspects of MSC function have been attributed to the paracrine effects of MSC derived extracellular vesicles (EVs). Although MSC EVs show great promise for regenerative medicine applications, insights into their uptake mechanisms by different target cells and the ability to control MSC EV properties for defined function in vivo have remained elusive knowledge gaps. The primary goal of this study is to elucidate how the basic properties of MSC derived EVs can be exploited for function-specific activity in regenerative medicine. Our first important observation is that, MSC EVs possess a common mechanism of endocytosis across multiple cell types. Second, altering the MSC state by inducing differentiation into multiple lineages did not affect the exosomal properties or endocytosis but triggered the expression of lineage-specific genes and proteins in vitro and in vivo respectively. Overall, the results presented in this study show a common mechanism of endocytosis for MSC EVs across different cell types and the feasibility to generate functionally enhanced EVs by modifications to parental MSCs., (Copyright © 2020 Huang, Kang, Narayanan, DiPietro, Cooper, Gajendrareddy and Ravindran.)

Demineralized bone matrix (DBM) is one of the most widely used bone graft materials in dentistry. However, the ability of DBM to reliably and predictably induce bone regeneration has always been a cause for concern. The quality of DBM varies greatly depending on several donor dependent factors and also manufacturing techniques. In order to standardize the quality and to enable reliable and predictable bone regeneration, we have generated a biomimetically-enhanced version of DBM (BE-DBM) using clinical grade commercial DBM as a control. We have generated the BE-DBM by incorporating a cell-derived pro-osteogenic extracellular matrix (ECM) within clinical grade DBM. In the present study, we have characterized the BE-DBM and evaluated its ability to induce osteogenic differentiation of human marrow derived stromal cells (HMSCs) with respect to clinical grade commercial DBM. Our results indicate that the BE-DBM contains significantly more pro-osteogenic factors than DBM and enhances HMSC differentiation and mineralized matrix formation in vitro and in vivo. Based on our results, we envision that the BE-DBM has the potential to replace DBM as the bone graft material of choice.

Freeze-drying is an effective means to control scaffold pore size and preserve its composition. The purpose of the present study was to determine the applicability of lyophilized Platelet-rich fibrin (LPRF) as a scaffold for craniofacial tissue regeneration and to compare its biological effects with commonly used fresh Platelet-rich fibrin (PRF). LPRF caused a 4.8-fold±0.4-fold elevation in Runt-related transcription factor 2 (Runx2) expression in alveolar bone cells, compared to a 3.6-fold±0.2-fold increase when using fresh PRF, and a more than 10-fold rise of alkaline phosphatase levels and mineralization markers. LPRF-induced Runx2 expression only occurred in alveolar bone and not in periodontal or dental follicle cells. LPRF also caused a 1.6-fold increase in osteoblast proliferation (p<0.001) when compared to fresh PRF. When applied in a rat craniofacial defect model for six weeks, LPRF resulted in 97% bony coverage of the defect, compared to 84% for fresh PRF, 64% for fibrin, and 16% without scaffold. Moreover, LPRF thickened the trabecular diameter by 25% when compared to fresh PRF and fibrin, and only LPRF and fresh PRF resulted in the formation of interconnected trabeculae across the defect. Together, these studies support the application of lyophilized PRF as a biomimetic scaffold for craniofacial bone regeneration and mineralized tissue engineering.

Objective: The face is a complex architectural structure in the body and is a high-risk site for fractures. Hospitalization is necessary for adequate treatment. The objective of this study is to examine hospitalization outcomes associated with reduction in facial fractures in the United States., Methods: The Nationwide Inpatient Sample (NIS) of the health care cost and utilization project for 2008 was used. This database provides weighted estimates of all hospitalizations in the United States, which approximates 39.88 million admissions in the entire United States. Hospital discharges with primary procedure ICD-9-CM codes for reduction in facial fractures were selected. Outcomes examined included hospitalization charges, length of stay, and causes of injuries. All estimates obtained from the sample were projected to national levels., Results: Reduction in facial fractures was performed as primary procedure in 21,244 hospitalizations. The total hospitalization charges were about $1.06 billion, and total hospitalization days was 93,808. About 80% of all hospitalizations occurred among men. The frequently occurring external causes of injuries leading to hospitalization for reduction in facial fractures include assault (36.5% of all hospitalizations), motor vehicle traffic accidents (16%), falls (15%), and other transportation accidents (3.5%). The frequently performed procedures were open reduction in mandibular fractures (52.2%), open reduction in facial fractures including those of orbital rim or wall (14.7%), closed reduction in mandibular fractures (12.1%), and open reduction in malar and zygomatic fractures (11.8%)., Conclusions: National hospitalization outcomes related to reduction in facial fractures indicate an extensive consumption of hospital resources. If hospital emergency room protocols and inpatient protocols relating to the most expensive fractures and longest hospital stays that we have identified can improve, this may lead to improved outcomes and a reduction in hospital charges for facial fractures., (© 2012 John Wiley & Sons A/S.)