Evaluating whether the proportional odds models to analyse ordinal outcomes in COVID-19 clinical trials is providing clinically interpretable treatment effects: A systematic review.

BACKGROUND: After an initial recommendation from the World Health Organisation, trials of patients hospitalised with COVID-19 often include an ordinal clinical status outcome, which comprises a series of ordered categorical variables, typically ranging from 'Alive and discharged from hospital' to 'Dead'. These ordinal outcomes are often analysed using a proportional odds model, which provides a common odds ratio as an overall measure of effect, which is generally interpreted as the odds ratio for being in a higher category. The common odds ratio relies on the assumption of proportional odds, which implies an identical odds ratio across all ordinal categories; however, there is generally no statistical or biological basis for which this assumption should hold; and when violated, the common odds ratio may be a biased representation of the odds ratios for particular categories within the ordinal outcome. In this study, we aimed to evaluate to what extent the common odds ratio in published COVID-19 trials differed to simple binary odds ratios for clinically important outcomes. METHODS: We conducted a systematic review of randomised trials evaluating interventions for patients hospitalised with COVID-19, which used a proportional odds model to analyse an ordinal clinical status outcome, published between January 2020 and May 2021. We assessed agreement between the common odds ratio and the odds ratio from a standard logistic regression model for three clinically important binary outcomes: 'Alive', 'Alive without mechanical ventilation', and 'Alive and discharged from hospital'. RESULTS: Sixteen randomised clinical trials, comprising 38 individual comparisons, were included in this study; of these, only 6 trials (38%) formally assessed the proportional odds assumption. The common odds ratio differed by more than 25% compared to the binary odds ratios in 55% of comparisons for the outcome 'Alive', 37% for 'Alive without mechanical ventilation', and 24% for 'Alive and discharged from hospital'. In addition, the common odds ratio systematically underestimated the odds ratio for the outcome 'Alive' by -16.8% (95% confidence interval: -28.7% to -2.9%, p = 0.02), though differences for the other outcomes were smaller and not statistically significant (-8.4% for 'Alive without mechanical ventilation' and 3.6% for 'Alive and discharged from hospital'). The common odds ratio was statistically significant for 18% of comparisons, while the binary odds ratio was significant in 5%, 16%, and 3% of comparisons for the outcomes 'Alive', 'Alive without mechanical ventilation', and 'Alive and discharged from hospital', respectively. CONCLUSION: The common odds ratio from proportional odds models often differs substantially to odds ratios from clinically important binary outcomes, and similar to composite outcomes, a beneficial common OR from a proportional odds model does not necessarily indicate a beneficial effect on the most important categories within the ordinal outcome.

Periradicular tissue fluid-derived biomarkers for apical periodontitis: An in vitro methodological and in vivo cross-sectional study.

BACKGROUND: Periradicular tissue fluid (PTF) offers a source of diagnostic, prognostic and predictive biomarkers for endodontic disease. AIMS: (1) To optimize basic parameters for PTF paper point sampling in vitro for subsequent in vivo application. (2) To compare proteomes of PTF from teeth with normal apical tissues (NAT) and asymptomatic apical periodontitis (AAP) using high-throughput panels. METHODOLOGY: (1) To assess volume absorbance, paper points (n = 20) of multiple brands, sizes and sampling durations were inserted into PBS/1%BSA at several depths. Wetted lengths (mm) were measured against standard curves to determine volume absorbance (µL). To assess analyte recovery, paper points (n = 6) loaded with 2 µL recombinant IL-1ß (15.6 ng/mL) were eluted into 250 µL: (i) PBS; (ii) PBS/1% BSA; (iii) PBS/0.1% Tween20; (iv) PBS/0.25 M NaCl. These then underwent: (i) vortexing; (ii) vortexing/centrifugation; (iii) centrifugation; (iv) incubation/vortexing/centrifugation. Sandwich-ELISAs determined analyte recovery (%) against positive controls. (2) Using optimized protocols, PTF was retrieved from permanent teeth with NAT or AAP after accessing root canals. Samples, normalized to total fluid volume (TFV), were analysed to determine proteomic profiles (pg/TFV) of NAT and AAP via O-link Target-48 panel. Correlations between AAP and diagnostic accuracy were explored using principal-component analysis (PCA) and area under receive-operating-characteristic curves (AUC [95% CI]), respectively. Statistical comparisons were made using Mann-Whitney U, anova and post hoc Bonferonni tests (α < .01). RESULTS: (1) UnoDent's 'Classic' points facilitated maximum volume absorbance (p < .05), with no significant differences after 60 s (1.6 µL [1.30-1.73]), 1 mm depth and up to 40/0.02 (2.2 µL [1.98-2.20]). For elution, vortexing (89.3%) and PBS/1% BSA (86.9%) yielded the largest IL-1ß recovery (p < .05). (2) 41 (NAT: 13; AAP: 31) PTF samples proceeded to analysis. The panel detected 18 analytes (CCL-2, -3, -4; CSF-1; CXCL-8, -9; HGF; IL-1ß, -6, -17A, -18; MMP-1, -12; OLR-1; OSM; TNFSF-10, -12; VEGF-A) in ≥75% of AAP samples at statistically higher concentrations (p < .01). CXCL-8, IL-1ß, OLR-1, OSM and TNFSF-12 were strongly correlated to AAP. 'Excellent' diagnostic performance was observed for TNFSF-12 (AUC: 0.94 [95% CI: 0.86-1.00]) and the PCA-derived cluster (AUC: 0.96 [95% CI: 0.89-1.00]). CONCLUSIONS: Optimized PTF sampling parameters were identified in this study. When applied clinically, high-throughput proteomic analyses revealed complex interconnected networks of potential biomarkers. TNFSF-12 discriminated periradicular disease from health the greatest; however, clustering analytes further improved diagnostic accuracy. Additional independent investigations are required to validate these findings.

Systematic comparison of machine learning algorithms to develop and validate predictive models for periodontitis.

AIM: The aim of this study was to compare the validity of different machine learning algorithms to develop and validate predictive models for periodontitis. MATERIALS AND METHODS: Using national survey data from Taiwan (n = 3453) and the United States (n = 3685), predictors of periodontitis were extracted from the datasets and pre-processed, and then 10 machine learning algorithms were trained to develop predictive models. The models were validated both internally (bootstrap sampling) and externally (alternative country's dataset). The algorithms were compared across six performance metrics ([i] area under the curve for the receiver operating characteristic [AUC], [ii] accuracy, [iii] sensitivity, [iv] specificity, [v] positive predictive value, and [vi] negative predictive value) and two methods of data pre-processing ([i] machine-learning-based feature selection and [ii] dimensionality reduction into principal components). RESULTS: Many algorithms showed extremely strong performance during internal validation (AUC > 0.95, accuracy > 95%). However, this was not replicated in external validation, where predictive performance of all algorithms dropped off drastically. Furthermore, predictive performance differed according to data pre-processing methodology and the cohort on which they were trained. CONCLUSIONS: Larger sample sizes and more complex predictors of periodontitis are required before machine learning can be leveraged to its full potential.

Trends in the prevalence of dental caries in the US pediatric population 2011-2020.

OBJECTIVE: The aim of this study was to provide statistics on the trends and changes in the distribution of dental caries in the United States (US) pediatric population for the 10-year period 2011 through 2020. STUDY DESIGN: Using data from the 2011 to 2020 National Health and Nutrition Examination Surveys, estimates were derived for the prevalence of decayed and filled teeth in the US population aged between 2 to 11 years. Analyses were stratified by primary and permanent dentition, and prevalence was assessed amongst the various sociodemographic and body mass index (BMI) subgroups. RESULTS: Over the 10-year period, the following changes were observed: the prevalence of decayed primary teeth has decreased from 14.1% to 12.2%, the prevalence of filled primary teeth has decreased from 29.8% to 26.1%, the prevalence of decayed permanent teeth has decreased from 5.2% to 2.7%, and the prevalence of filled permanent teeth has decreased from 16.1% to 12.3%. Despite these decreases in prevalence, there remains substantial inequality in how the disease is distributed, with those from ethnic minorities, poorer households, and with a non-normal BMI carrying the majority of disease burden. CONCLUSIONS: The prevalence of dental caries has decreased over the past 10 years, but there is still inequality in disease distribution.

Clarithromycin as an adjunct to periodontal therapy: a systematic review and meta-analysis.

OBJECTIVE: To collate the literature evaluating the efficacy of clarithromycin as an adjunct to non-surgical periodontal therapy and conduct meta-analyses for changes in probing pocket depth (PPD) and clinical attachment level (CAL). METHODS: Five electronic databases were searched from inception to May 2020 (PubMed, Cochrane CENTRAL, EMBASE via OVID, Web of Science and OpenGrey). Clinical outcomes were extracted, pooled and meta-analyses conducted using mean difference with standard deviations. RESULTS: Systemic delivery: 0.65 mm (95% CI: 0.02 to 1.27 mm) mean additional PPD reduction was observed at 3 months and 0.28 mm (95% CI: -0.32 to 0.87 mm) at 6 months. 0.41 mm (95% CI: -0.12 to 0.95 mm) mean additional CAL gain was observed at 3 months, and 0.16 mm (95% CI: -0.41 to 0.74 mm) at 6 months. Increased risk of adverse events was observed; RR: 5.13 (95% CI: 0.63 to 41.98). Local delivery: 1.01 mm (95% CI: 0.84 to 1.17 mm) mean additional PPD reduction was observed at 3 months, and 1.20 mm (95% CI: 0.76 to 1.64 mm) at 6 months. 0.56 mm (95% CI: 0.46 to 0.66 mm) mean additional CAL gain was observed at 3 months, and 0.83 mm (95% CI: 0.65 to 1.02 mm) at 6 months. No adverse events were observed. CONCLUSIONS: The use of locally delivered clarithromycin significantly improves treatment outcomes.

Indocyanine green-mediated antimicrobial photodynamic therapy as an adjunct to periodontal therapy: a systematic review and meta-analysis.

OBJECTIVES: The aim of this systematic review and meta-analysis was to evaluate the efficacy of indocyanine green-mediated photodynamic therapy (ICG-PDT) as an adjunct to non-surgical periodontal therapy (NSPT), in the management of chronic periodontitis. MATERIALS AND METHODS: Four electronic databases (PubMed, Cochrane Central Register of Controlled Trials, Embase via OVID, Web of Science) were searched for randomised controlled trials comparing NSPT with ICG-PDT to NSPT without laser therapy. Primary outcome measures were changes in probing pocket depth (PPD) and clinical attachment level (CAL). Clinical outcomes were extracted and pooled from 7 eligible trials and meta-analyses conducted using mean difference with standard deviations. RESULTS: For PPD, adjunctive ICG-PDT resulted in a mean additional reduction of 1.17 mm (95% CI: 0.67-1.66 mm) at 3 months and a mean additional reduction of 1.06 mm (95% CI: 0.54-1.57 mm) at 6 months. For CAL, adjunctive ICG-PDT resulted in a mean additional gain of 0.70 mm (95% CI: 0.17-1.23 mm) at 3 months and a mean additional gain of 1.03 mm (95% CI: 0.83-1.24 mm) at 6 months. No adverse events were reported in any studies. CONCLUSIONS: The adjunctive use of ICG-PDT in NSPT results in improved treatment outcomes at 3 and 6 months post-therapy. Further investigation is needed to evaluate variables such as different photosensitiser concentrations and adjusting parameters associated with the light source. CLINICAL RELEVANCE: Indocyanine green-based photosensitisers may be a novel, clinically efficacious agent for use in the management of periodontitis.

Boric acid as an adjunct to periodontal therapy: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy of boric acid as an adjunct to non-surgical periodontal therapy, in comparison with a placebo adjunct, in terms of changes in probing pocket depth (PPD) and clinical attachment level (CAL), in patients with periodontitis. METHODS: Four electronic databases were searched from inception to May 2020 (PubMed, Cochrane CENTRAL, EMBASE via OVID and Web of Science). Clinical outcomes were extracted, pooled and meta-analyses conducted using mean difference with standard deviations. RESULTS: For PPD, a mean additional reduction of 0.58 mm (95% CI: -0.03-1.19 mm, p = 0.06) was observed at 3 months and a mean additional reduction of 1.18 mm (95% CI: 0.97-1.40 mm, p < 0.05) at 6 months, compared with placebo. For CAL, a mean additional gain of 0.62 mm (95% CI: -0.07-1.32 mm, p = 0.08) was observed at 3 months and a mean additional gain of 1.24 mm (95% CI: 0.89-1.58 mm, p < 0.05) at 6 months, compared with placebo. No adverse events were reported in any studies. CONCLUSIONS: The adjunctive use of boric acid in non-surgical periodontal therapy results in improved treatment outcomes at 3 and 6 months, with no adverse events reported.

The intersections of socioeconomic position, gender, race/ethnicity and nationality in relation to oral conditions among American adults.

OBJECTIVE: The objective of the study was to evaluate how gender, socioeconomic position (SEP), race/ethnicity and nationality intersect to structure social inequalities in adult oral health among American adults. METHODS: Data from adults aged 20 years or over who participated in the National Health and Nutrition Examination Survey (NHANES) 2009-2018 were analysed. The outcomes were poor self-rated oral health and edentulism among all adults (n = 24 541 and 21 446 participants, respectively) and untreated caries and periodontitis among dentate adults (n = 16 483 and 9829 participants, respectively). A multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA) was conducted for each outcome, by nesting individuals within 48 intersectional strata defined as combinations of gender, SEP, race/ethnicity and nationality. Intersectional measures included the variance partition coefficient (VPC), the proportional change in variance (PCV) and predicted excess probability due to interaction. RESULTS: Substantial social inequalities in the prevalence of oral conditions among adults were found, which were characterized by high between-stratum heterogeneity and outcome specificity. The VPCs of the simple intersectional model showed that 9.4%-12.7% of the total variance in the presentation of oral conditions was attributed to between-stratum differences. In addition, the PCVs from the simple intersectional model to the intersectional interaction model showed that 84.1%-97.1% of the stratum-level variance in the presentation of oral conditions was attributed to the additive effects of gender, SEP, race/ethnicity and nationality. The point estimates of the predictions for some intersectional strata were suggestive of an intersectional interaction effect. However, the 95% credible intervals were very wide and the estimations inconclusive. CONCLUSIONS: This analysis highlights the value of the intersectionality framework to understand heterogeneity in social inequalities in oral health. These inequalities were mainly due to the additive effect of the social identities defining the intersectional strata, with no evidence of interaction effects.

Non-Pharmacological Therapies for Post-Viral Syndromes, Including Long COVID: A Systematic Review.

BACKGROUND: Post-viral syndromes (PVS), including Long COVID, are symptoms sustained from weeks to years following an acute viral infection. Non-pharmacological treatments for these symptoms are poorly understood. This review summarises the evidence for the effectiveness of non-pharmacological treatments for PVS. METHODS: We conducted a systematic review to evaluate the effectiveness of non-pharmacological interventions for PVS, as compared to either standard care, alternative non-pharmacological therapy, or placebo. The outcomes of interest were changes in symptoms, exercise capacity, quality of life (including mental health and wellbeing), and work capability. We searched five databases (Embase, MEDLINE, PsycINFO, CINAHL, MedRxiv) for randomised controlled trials (RCTs) published between 1 January 2001 to 29 October 2021. The relevant outcome data were extracted, the study quality was appraised using the Cochrane risk-of-bias tool, and the findings were synthesised narratively. FINDINGS: Overall, five studies of five different interventions (Pilates, music therapy, telerehabilitation, resistance exercise, neuromodulation) met the inclusion criteria. Aside from music-based intervention, all other selected interventions demonstrated some support in the management of PVS in some patients. INTERPRETATION: In this study, we observed a lack of robust evidence evaluating the non-pharmacological treatments for PVS, including Long COVID. Considering the prevalence of prolonged symptoms following acute viral infections, there is an urgent need for clinical trials evaluating the effectiveness and cost-effectiveness of non-pharmacological treatments for patients with PVS. REGISTRATION: The study protocol was registered with PROSPERO [CRD42021282074] in October 2021 and published in BMJ Open in 2022.

Update on the prevalence of untreated caries in the US adult population, 2017-2020.

BACKGROUND: Untreated caries is a prevalent disease that is associated with a substantial health and economic burden. Many past efforts have assessed the epidemiology of untreated caries, and this study provides the most up-to-date figures on the distribution and determinants of the disease in the adult US population for the period 2017 through 2020. METHODS: Using data from the 2017-2020 National Health and Nutrition Examination Survey, the author derived estimates for untreated caries prevalence in the adult US population. The author conducted subgroup analyses to assess how the epidemiology differed between coronal and root caries and how the disease was distributed among population subgroups. RESULTS: On the basis of a weighted sample representative of 193.5 million adults, the prevalence of untreated caries was found to be 21.3%. Specific prevalence of coronal and root caries were 17.9% and 10.1%, respectively. Caries was most prevalent in those aged 30 through 39 years (25.2%) and 40 through 49 years (22.3%), men (23.5%), those of other (36.5%) or non-Hispanic Black (35.6%) race or ethnicity, those with family income to poverty ratio of 0.5 through 1.0 (46.2%) or less than 0.5 (37.3%), those with educational attainment less than high school graduation (39.6%), those who did not have health insurance (42.1%), and those who were underweight (25.1%) or obese (23.5%). CONCLUSIONS: Untreated caries is present in more than 1 in 5 adults within the US population and is disproportionately distributed among those of lower socioeconomic status. PRACTICAL IMPLICATIONS: There is a substantial unmet health care need in the US adult population for the prevention and management of untreated caries, and public health efforts should aim particularly to address disease within those subgroups who are at a disproportionately high risk.

Removable partial dentures and mortality among partially edentulous adults.

OBJECTIVES: The aim of this study was to evaluate whether the use of removable partial dentures (RPDs) has an effect on long-term survival outcomes amongst partially edentulous adults. METHODS: Data were extracted from the Third National Health and Nutrition Examination Survey and linked to public-use mortality files for the period up to 2019. Partially edentulous adults with fewer than 20 teeth were included. RPD use and dentition status were determined by clinical examination. The cohort was propensity score weighted to create a sample which was balanced across 27 covariates (sociodemographics, health behaviors and insurance, laboratory markers, and general health status). Survival analysis was undertaken to compute absolute (mortality rate and median survival time) and relative (event time ratio [ETR]) measures of exposure effect. RESULTS: The analyzed cohort included 1246 participants, which equated to 22,557 person-years of follow-up. The difference in all-cause mortality rate between RPD wearers and non-wearers was found to be -6.5 (95% CI: -11.6 to -1.4), with the median survival time in RPD wearers being 3.1 years longer (20.3 years versus 17.2 years). A 26% increase in survival time was observed in RPD wearers (ETR: 1.26, 95% CI: 1.17 to 1.37) and it was found that, for every 7.5 individuals treated with RPDs, one death would be prevented after 10 years of treatment. CONCLUSIONS: The use of RPDs may have long-term benefits in reducing mortality amongst adults with a non-functional dentition, but further research is needed to validate these findings and assess the factors mediating the relationship. CLINICAL SIGNIFICANCE: The use of RPDs may have long-term benefits in reducing mortality amongst adults with a non-functional dentition.

Exploiting Dentine Matrix Proteins in Cell-Free Approaches for Periradicular Tissue Engineering.

The recent discovery of mesenchymal stem cells within periapical lesions (PL-MSC) has presented novel opportunities for managing periradicular diseases in adult teeth by way of enhancing tissue regeneration. This discovery coincides with the current paradigm shift toward biologically driven treatment strategies in endodontics, which have typically been reserved for non-vital immature permanent teeth. One such approach that shows promise is utilizing local endogenous non-collagenous dentine extracellular matrix components (dECM) to recruit and upregulate the intrinsic regenerative capacity of PL-MSCs in situ. At picogram levels, these morphogens have demonstrated tremendous ability to enhance the cellular activities in in vitro and in vivo animal studies that would otherwise be necessary for periradicular regeneration. Briefly, these include proliferation, viability, migration, differentiation, and mineralization. Therefore, topical application of dECMs during ortho- or retrograde root canal treatment could potentially enhance and sustain the regenerative mechanisms within diseased periapical tissues that are responsible for attaining favorable clinical and radiographic outcomes. This would provide many advantages when compared with conventional antimicrobial-only therapies for apical periodontitis (AP), which do not directly stimulate healing and have had stagnant success rates over the past five decades despite significant advances in operative techniques. The aim of this narrative review was to present the novel concept of exploiting endogenous dECMs as clinical tools for treating AP in mature permanent teeth. A large scope of literature was summarized to discuss the issues associated with conventional treatment modalities; current knowledge surrounding PL-MSCs; composition of the dECM; inductive potentials of dECM morphogens in other odontogenic stem cell niches; how treatment protocols can be adapted to take advantage of dECMs and PL-MSCs; and finally, the challenges currently impeding successful clinical translation alongside directions for future research. Impact statement Apical periodontitis (AP) is an inflammatory condition that is associated with a great degree of morbidity and ultimately leads to tooth loss. The purpose of this review was to summarize the current evidence pertaining to stem cell therapy in endodontics and present a novel clinical methodology through which they may be utilized to address AP. A comprehensive overview of the basic science, clinical translation, and potential challenges are presented in this review.

Non-pharmacological therapies for postviral syndromes, including Long COVID: a systematic review and meta-analysis protocol.

INTRODUCTION: Postviral syndromes (PVS) describe the sustained presence of symptoms following an acute viral infection, for months or even years. Exposure to the SARS-CoV-2 virus and subsequent development of COVID-19 has shown to have similar effects with individuals continuing to exhibit symptoms for greater than 12 weeks. The sustained presence of symptoms is variably referred to as 'post COVID-19 syndrome', 'post-COVID condition' or more commonly 'Long COVID'. Knowledge of the long-term health impacts and treatments for Long COVID are evolving. To minimise overlap with existing work in the field exploring treatments of Long COVID, we have only chosen to focus on non-pharmacological treatments. AIMS: This review aims to summarise the effectiveness of non-pharmacological treatments for PVS, including Long COVID. A secondary aim is to summarise the symptoms and health impacts associated with PVS in individuals recruited to treatment studies. METHODS AND ANALYSIS: Primary electronic searches will be performed in bibliographic databases including: Embase, MEDLINE, PyscINFO, CINAHL and MedRxiv from 1 January 2001 to 29 October 2021. At least two independent reviewers will screen each study for inclusion and data will be extracted from all eligible studies onto a data extraction form. The quality of all included studies will be assessed using Cochrane risk of bias tools and the Newcastle-Ottawa grading system. Non-pharmacological treatments for PVS and Long COVID will be narratively summarised and effect estimates will be pooled using random effects meta-analysis where there is sufficient methodological homogeneity. The symptoms and health impacts reported in the included studies on non-pharmacological interventions will be extracted and narratively reported. ETHICS AND DISSEMINATION: This systematic review does not require ethical approval. The findings from this study will be submitted for peer-reviewed publication, shared at conference presentations and disseminated to both clinical and patient groups. PROSPERO REGISTRATION NUMBER: The review will adhere to this protocol which has also been registered with PROSPERO (CRD42021282074).

Symptoms and risk factors for long COVID in non-hospitalized adults.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long COVID. We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02-8.39), hair loss (3.99, 3.63-4.39), sneezing (2.77, 1.40-5.50), ejaculation difficulty (2.63, 1.61-4.28) and reduced libido (2.36, 1.61-3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.

The role of insulin-like growth factors in modulating the activity of dental mesenchymal stem cells.

Regenerative treatment protocols are an exciting prospect in the management of oral pathology, as they allow for tissues to be restored to their original form and function, as compared to the reparative healing mechanisms which currently govern the outcomes of the majority of dental treatment. Stem cell therapy presents with a great deal of untapped potential in this pursuit of tissue regeneration, and, in particular, mesenchymal stem cells (MSCs) derived from dental tissues are of specific relevance with regards to their applications in engineering craniofacial tissues. A number of mediatory factors are involved in modulating the actions of dental MSCs, and, of these, insulin like growth factors (IGFs) are known to have potent effects in governing the behavior of these cells. The IGF family comprises a number of primary ligands, receptors, and binding proteins which are known to modulate the key properties of dental MSCs, such as their proliferation rates, differentiation potential, and mineralisation. The aims of this review are three-fold: (i) to present an overview of dental MSCs and the role of growth factors in modulating their characteristics, (ii) to discuss in greater detail the specific role of IGFs and the benefits they may convey for tissue engineering, and (iii) to provide a summary of potential for in vivo clinical translation of the current in vitro body of evidence.