Decreasing Tryptophan and Increasing Neopterin Plasma Levels During Pregnancy are Associated with High First Trimester Porphyromonas gingivalis K-Serotype IgG Serointensity in a Cohort of Hispanic Women.

BACKGROUND: Immune activation or high levels of stress may lead to increased metabolism of tryptophan during pregnancy. Porphyromonas gingivalis (Pg), the "keystone" periodontal pathogen, induces immune and indoleamine 2,3-dioxygenase (IDO) activation. Thus, we hypothesized that larger gestational decreases in tryptophan and elevations in neopterin and kynurenine would occur in pregnant women with elevated IgG antibodies to Pg capsular (K) serotypes. METHODS: Venous blood of 52 Hispanic pregnant women with a mean age (SD) of 31.8 (5.9) years was sampled once per trimester of pregnancy (V1, V2, V3), and plasma was obtained and stored. ELISAs were used to measure Pg capsular (K) serotype IgG serointensity (V1 only) and neopterin levels (V1-V3). Tryptophan and kynurenine (V1-V3) were measured with high-performance liquid chromatography. The participants having IgG serointensity for any of the seven Pg K serotypes in the highest quartile were defined as the "High PgK_IgG" group and those having IgG serointensity for all K serotypes in the lowest three quartiles were defined as the "Low PgK_IgG" group. Statistics included multivariable linear and nonparametric methods. RESULTS: Significant decreases in plasma tryptophan levels and increases in neopterin during gestation were found in "High PgK_IgG" women but not in "Low PgK_IgG" women. Kynurenine changes were not significantly different between the two groups. CONCLUSION: If replicated in larger studies and further characterized clinically, radiologically, and microbiologically, our results may potentially lead to novel interventional targets, as well as the development of more complete prognostic and predictive interactive biomarkers for adverse obstetrical outcomes and peripartum depression, and their prevention.

Oral Inflammatory Burden and Carotid Atherosclerosis Among Stroke Patients.

INTRODUCTION: This study aimed to test the hypothesis that oral inflammatory burden (OIB) is independently associated with the carotid atherosclerotic burden (CAB) among individuals with ischemic stroke (IS) or transient ischemic attack (TIA). METHODS: This cross-sectional observational study included 240 hospital patients with the diagnosis of IS or TIA. The main exposures were apical periodontitis (AP), root canal treatment (RCT), and crestal alveolar (periodontal) bone loss (BL), and the main outcome was the CAB. Exposure and outcome variables were measured through a head and neck multidetector computed tomography angiography and CAB was dichotomized in <50% and ≥50% vessel occlusion. OIB scored as a composite measure of the endodontic and periodontal disease exposure. Hospital health records provided information on sociodemographic and medical covariates. Prevalence ratios (PRs) were calculated through Poisson regression models, estimating the relationship between the oral exposures and CAB, with = 5%. RESULTS: Mean age was 62.15 ± 13.1 years, with 56.7% men. Univariate analyses showed that AP ≥2 (PR = 1.83; 95% confidence interval [CI], 1.05-3.17) and endodontic burden (EB) (AP and/or RCT ≥ 2) (PR = 1.98; 95% CI, 1.13-3.47) were associated with CAB ≥50%. Multivariate models, adjusted for sociodemographic and medical covariates, revealed that pooled periodontal and endodontic parameters (OIB = BL ≥ 5 mm and EB ≥ 2) were independently associated with CAB ≥ 50% (PR = 2.47; 95% CI, 1.04-5.87). CONCLUSION: A higher OIB was independently associated with increased levels of CAB among hospital patients with IS or TIA. The combination of endodontic and periodontal parameters strengthened the observed association and should be evaluated in future studies on the relationship between oral health and cardiovascular outcomes.

Effecting change in academic dentistry through small groups.

PURPOSE/OBJECTIVE: The work of faculty, staff, and students is driven by their alignment with an institution's vision and purpose, as set forth in its strategic plan. Any plan that calls for innovative growth must address certain aspects of organizational culture as roadblocks to success and should foster relationship building to achieve long-standing progress. This demonstration project investigates a method for effecting change through a Small Group Initiative (SGI). METHODS: Representatives from faculty and staff were selected by purposive sampling, placed into eight groups of six, and one member of each group was made a facilitator to participate in or facilitate monthly structured discussion-based meetings for a 1-year time period. Participants read one chapter a month of 12: The Elements of Great Managing, which corresponds to the Gallup Q12 Employee Engagement survey that each participant completed at the beginning and end of the program. RESULTS: Findings indicate an overall increase in participant levels of employee engagement and increased levels of personal ownership in regard to the strategic plan after participating in the SGI. CONCLUSIONS: Many other institutional efforts aimed at the advancement of school-wide vision and employee engagement can be cumbersome to implement and require a substantial allocation of resources. The SGI, however, requires minimal resources, limited infringement on regular activity, and minimal direct cost to implement. These factors suggest that the SGI could be tailored to meet specific needs of leadership and may have broad-based applicability across various academic settings.

'Face time' for the first time: Video communication between relatives and junior doctors in the COVID-19 pandemic.

Working on a COVID-19 ward presents a number of challenges to staff, with communication between families, patients and staff being highlighted as a key challenge. Novel methods are needed to overcome the barriers presented by COVID-19, with many turning to technology to offer solutions. Recognising these challenges as an area for improvement on our own ward, we sought to introduce new methods of communication to improve patient, relative and staff understanding and wellbeing. Through our own experiences and a discussion of the literature on this topic, we have identified some key themes which we believe can assist in the development of communication strategies in the developing pandemic.

To scan or not to scan - D-dimers and computed tomography pulmonary angiography in the era of COVID-19.

The COVID-19 pandemic has had many ramifications on healthcare delivery and practice. As part of this, utilising biomarkers to risk stratify patients has become increasingly popular. During the COVID-19 pandemic the use of D-dimer has increased due to the evidence of COVID-19 induced thrombo-embolic disease. We evaluated the use of D-dimer on all hospital admissions during the peak of the pandemic and evaluated its sensitivity in diagnosing pulmonary embolic disease (PE). Patients without COVID-19 infection were as likely to have evidence of PE as their COVID-positive counterparts. However, the sensitivity of a D-dimer was higher in COVID-positive patients at a lower D-dimer level (>1,500 µg/L, sensitivity 81%, specificity 70%) than in those without clinical, immunological or radiological evidence of COVID-19 infection (D-dimer >2,000 µg/L, sensitivity 80%, specificity 76%). These data suggest higher D-dimer thresholds should be considered for the exclusion of pulmonary emboli.

Quantile regression to estimate the survivor average causal effect of periodontal treatment effects on birthweight and gestational age.

BACKGROUND: Survival average causal effect (SACE) can give valid estimates of the periodontal treatment effect on birth outcomes in randomized controlled trials when fetal losses are unequal across the treatment arms. A regression-based method to estimate SACE using ordinary least squares (OLS) regression can be biased if the treatment effect varies across the outcome distribution. In this case quantile regression may be a suitable alternative. METHODS: We compared OLS and quantile regression models estimating SACE to calculate the effect of periodontal treatment on birthweight and gestational age in secondary analyses of publicly available Obstetrics and Periodontal Therapy (OPT) trial data. RESULTS: Periodontal treatment tended to increase birthweight and gestational age at the lowest quantiles, remained flat in the middle quantiles, and trended to decrease both birthweight and gestational age in the highest quantiles. In quantile regression models estimating SACE the ß-coefficients: 95% confidence intervals (CI) for the 5th, 50th, and 95th percentiles were 277.5:  -141.0 to 696.0 g, 1.4: -107 to 110.3 g, and -84: -344 to 175.3 g for birthweight, and 0.6: -1.0 to 2.2 weeks, -0.1: -0.5 to 0.2 weeks, and -0.6: -1.0 to -0.1 weeks for gestational age. Estimates from OLS models estimating SACE were close to the null, ß: 95% CI -4.7: 132.3 to 123.0 g for birthweight, and 0.03: -0.72 to 0.78 weeks for gestational age. CONCLUSIONS: OLS models to evaluate SACE for periodontal treatment effects on birthweight and gestational age may be biased towards the null. Quantile regression may be a preferable alternative.

Evaluation of poly lactic-co-glycolic acid-coated ß-tricalcium phosphate for alveolar ridge preservation: A multicenter randomized controlled trial.

BACKGROUND: Alveolar ridge preservation via socket grafting (ARP-SG) is indicated to attenuate physiologic alveolar bone resorption as a consequence of tooth extraction. However, a specific bone grafting material that is patently superior has not been identified yet. The aim of this randomized controlled trial was to evaluate the efficacy of a moldable alloplastic graft, Poly Lactic-Co-Glycolic Acid-Coated ß-Tricalcium Phosphate (PLGA-ß-TCP), for ARP purposes [Group A] compared to freeze-dried bone allograft (FDBA) particles covered with a rapidly absorbable collagen dressing (RACD) (Group B) in function of a panel of radiographic, histomorphometric, and implant-related outcomes. METHODS: Patients in need of extraction of a single posterior tooth (premolar or molar) and subsequent replacement with a dental implant were recruited and randomly allocated into one of the two treatment groups. Follow-up visits took place at 1, 2, 4, 8, and 16 weeks. Cone-beam Computed Tomography (CBCT) scans were obtained at baseline and at 16 weeks. Sites were re-entered at 20 weeks for bone core biopsy harvesting and subsequent implant placement. After delivery of the final implant-supported restoration, follow-up visits were scheduled at 6 and 12 months to monitor peri-implant tissue health and marginal bone levels using standardized intraoral periapical radiographs. RESULTS: A total of 45 patients were initially enrolled in the study, of whom 43 received an implant and 32 completed the study. Healing was uneventful in all sites after ARP-SG and implant placement. No site required bone augmentation to allow for implant placement. CBCT scan analyses showed no statistically significant differences between groups in terms of reduction of horizontal width, midbuccal / midlingual height and ridge volume. Histomorphometric assessments revealed a statistically significant difference between both groups in terms of mineralized tissue formation (Group A = 27.0% ± 22.1% versus Group B = 38.2% ± 12.5%; P < 0.05). On the contrary, no significant differences were observed regarding percent of remaining bone grafting material and non-mineralized tissue. No implant failed throughout the study period and marginal bone level change was negligible in both groups. CONCLUSIONS: Although a higher proportion of mineralized tissue was associated with the use of FDBA+RACD compared to PLGA-ß-TCP alone, both ARP-SG approaches rendered comparable outcomes in terms of maintenance of alveolar bone dimensions, feasibility of implant placement, implant survival, and peri-implant bone level stability up to 12 months post-loading.

Adherence to and acceptability of three alcohol-free, antiseptic oral rinses: A community-based pilot randomized controlled trial among pregnant women in rural Nepal.

OBJECTIVES: Antiseptic oral rinses have been evaluated as interventions to reduce the risk of adverse pregnancy outcomes associated with periodontal disease in pregnant women. Oral rinse use is not common in Nepal or other countries in South Asia, where the prevalence of adverse pregnancy outcomes is high. Understanding whether pregnant women in rural communities in this region would incorporate rinse use into their daily teeth cleaning routine is an important prerequisite to future research on this topic in South Asia. METHODS: We conducted a community-based pilot randomized controlled trial of three alcohol-free, antiseptic oral rinses among pregnant women <22 weeks pregnant in rural Nepal with the aim of assessing rinse acceptability, adherence, and effect on clinical periodontal measures. At baseline, participants underwent a clinical periodontal examination, and then were classified as healthy or having at least mild gingivitis (≥1 site with probing depth (PD) 3 mm and bleeding on probing (BOP) or ≥4 mm (PD)). Participants were stratified by periodontal status and randomized within each exposure category to chlorhexidine (CHX) (0.12%), cetylpyridinium chloride (CPC) (0.05%), salt and water (NaCl), or control (no rinse). Rinse participants were followed weekly for 12 weeks, and all participants underwent a second periodontal examination and answered a questionnaire. RESULTS: Pregnant women in the rural Terai region of Nepal showed high adherence to (mean weekly rinse use: 185 mL (standard deviation: 66 mL)) a recommended 210 mL and acceptability of all three rinses. Participants reported greater frequency of tooth brushing with toothpaste and improvements in other recommended oral hygiene behaviours. CHX significantly reduced rates of gingivitis (defined as a participant with BOP ≥ 10% of sites) and the extent of BOP (gingivitis at the end of follow-up for CHX vs control: RR 0.37, 95% CI: 0.16, 0.84). CPC and NaCl rinse groups had rates of gingivitis and extent of BOP similar to the control group (gingivitis at the end of follow-up for CPC: RR 0.81, 95% CI: 0.47, 1.38; NaCl: RR 0.92, 95% CI: 0.55, 1.56). CONCLUSIONS: Adherence to and acceptability of three alcohol-free, antiseptic oral rinses were high among pregnant women in rural Nepal. Among participants with mild gingivitis at baseline, CHX rinse was most effective at reducing signs of disease compared to the control group. Oral rinse should be considered as a supplement to current oral self-care routines for pregnant women in settings where rinse use is uncommon and access to oral health services is limited.

Risk of preterm birth associated with maternal gingival inflammation and oral hygiene behaviours in rural Nepal: a community-based, prospective cohort study.

OBJECTIVES: Observational studies have identified associations between periodontitis and adverse pregnancy outcomes, but randomised controlled trials evaluating the efficacy of periodontal therapy have yielded inconsistent results. Few studies have explored relationships between gingival inflammation and these outcomes or been conducted in rural, low-income communities, where confounding risk factors differ from other settings. METHODS: We conducted a community-based, prospective cohort study with the aim of estimating associations between the extent of gingival inflammation in pregnant women and incidence of preterm birth in rural Nepal. Our primary exposure was gingival inflammation, defined as bleeding on probing (BOP) ≥10%, stratified by BOP <30% and BOP ≥30%. A secondary exposure, mild periodontitis, was defined as ≥2 interproximal sites with probing depth (PD) ≥4 mm (different teeth) or one site with PD ≥5 mm. Our primary outcome was preterm birth (<37 weeks gestation). We used Poisson regression to model this relationship, adjusting for potential confounders. RESULTS: Of 1394 participants, 554 (39.7%) had gingival inflammation, 54 (3.9%) mild periodontitis and 197 (14.1%) delivered preterm. In the adjusted regression model, increasing extent of gingival inflammation was associated with a non-significant increase in risk of preterm birth (BOP ≥30% vs no BOP: adjusted relative risk (aRR) 1.37, 95% CI: 0.81 to 2.32). A secondary analysis, stratifying participants by when in pregnancy their oral health status was assessed, showed an association between gingival inflammation and preterm birth among women examined in their first trimester (BOP ≥30% vs no BOP: aRR 2.57, 95% CI: 1.11 to 5.95), but not later in pregnancy (BOP ≥30% vs no BOP: aRR 1.05, 95% CI: 0.52 to 2.11). CONCLUSIONS: Gingival inflammation in women examined early in pregnancy and poor oral hygiene behaviours were risk factors for preterm birth. Future studies should evaluate community-based oral health interventions that specifically target gingival inflammation, delivered early in or before pregnancy, on preterm birth. TRIAL REGISTRATION NUMBER: Nepal Oil Massage Study, NCT01177111.

Immediate Tooth Replacement Therapy in Postextraction Sockets: A Comparative Prospective Study on the Effect of Variable Platform-Switched Subcrestal Angle Correction Implants.

Immediate tooth replacement therapy (ITRT), ie, immediate implant placement and provisional restoration in postextraction sockets, has been shown to achieve favorable outcomes in reference to soft tissue stability and esthetics. However, avoiding socket perforation with uniaxial implants in the anterior maxilla can be challenging due to the inherent anatomy. Dual or co-axis subcrestal angle correction (SAC) implants have been developed to change the restorative angle of the clinical crown restoration subcrestally at the implant-abutment interface to enhance the incidence of screw-retained definitive restorations. An additional benefit of this macrodesign implant feature is variable platform switching (VPS) that increases soft tissue gap distance above the implant platform. The purpose of this prospective study on ITRT in maxillary anterior postextraction sockets was to investigate the effect of SAC with VPS (SAC/VPS) compared to conventional platform-switch-design implants (PS) relative to ridge dimension stability and peri-implant soft tissue thickness. A total of 29 patients had undergone ITRT and received either a PS or SAC/VPS implant; previously described measurements were made compared to the contralateral natural tooth sites. When the comparison of buccal soft tissue thickness was made, SAC/VPS showed a greater increase compared to PS (3.12 mm vs 2.39 mm, respectively) with statistical significance (P = .05). The increase was independent from periodontal phenotype. Therefore, SAC/VPS may increase peri-implant soft tissue thickness and help minimize recession following ITRT.

Feasibility of training community health workers to conduct periodontal examinations: a validation study in rural Nepal.

BACKGROUND: In many low- and middle-income countries, insufficient human resources limit access to oral health services. Shifting clinical tasks to less specialized health professionals, such as community health workers, has been used as a strategy to expand the health workforce, especially in remote or underserved locations. The objective of this study was to evaluate the validity of periodontal examinations conducted by auxiliary nurse midwives in a rural home setting in Nepal. METHODS: Twenty-one pregnant women < 26 weeks gestation from Sarlahi District, Nepal, underwent full mouth periodontal examinations measuring probing depth (PD) and bleeding on probing (BOP) on 6 sites per tooth by one of five auxiliary nurse midwives, who were trained for this study but had no previous training in dentistry. After a 15-min break, each participant was examined again by an experienced dentist. Measures of validity for PD and BOP were calculated comparing the pooled and individual auxiliary nurse midwives to the dentist. A multivariable GEE model estimated the effect of periodontal characteristics on agreement between the auxiliary nurse midwives and the dentist. RESULTS: Participant mean age was 22 years (SD: ±3 years), mean PD was 1.4 mm (SD: 03 mm), and 86% of women had BOP (according to the dentist). Percent agreement, weighted kappa scores, and intraclass correlation coefficients for PD, with an allowance of ±1 mm, exceeded 99%, 0.7, and 0.9, respectively, indicating an acceptable level of agreement. Auxiliary nurse midwives tended to report higher PD scores relative to the dentist, although this over-estimation was small and unlikely to impact population-based estimates of important indicators of oral health status. GEE regression modeling indicated similar agreement for mandible vs. maxilla, left vs. right side, and PD (≤2 mm, > 2 mm), and lower agreement for posterior teeth and lingual and proximal sites. CONCLUSION: Auxiliary nurse midwives were able to accurately conduct periodontal examinations in a rural home setting, suggesting the potential to shift tasks away from highly trained dentists and periodontal examiners in low-resource communities. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01177111 (Nepal Oil Massage Study); registered on August 6th, 2010.

Tooth loss is associated with atherosclerosis and a poorer functional outcome among stroke patients.

OBJECTIVES: The purpose of the study was twofold: (1) to test the hypothesis that tooth loss is independently associated with carotid atherosclerotic burden (CAB) among individuals with ischemic stroke (IS) or transient ischemic attack (TIA) and (2) to test the association between tooth loss and disability following the occurrence of cerebral ischemia. MATERIALS AND METHODS: This observational study included 418 patients with IS or TIA. Tooth loss and the CAB were measured through a head and neck multidetector computed tomography angiography. CAB was analyzed in both common, internal, and external carotid arteries and classified in five levels of vascular occlusion. The modified Rankin Scale (mRS) was used to evaluate the functional outcome at patient discharge. Health records provided information on sociodemographic and medical covariates. The association between CAB and tooth loss, as well as between tooth loss and subtypes of cerebral ischemia were estimated through Poisson regression. Cox regression was carried out to evaluate the association between tooth loss and the mRS, with α = 5%. RESULTS: Mean age was 65.6 ± 13.8 years, with 52.4% males. Multivariate analyses revealed that severe tooth loss (> 23 missing teeth) was independently associated with CAB ≥ 50% (PR = 2.86, 95% CI = 1.19-6.89) and mRS scores (> 2) (HR = 1.97, 95% CI = 1.10-3.75). CONCLUSION: Tooth loss was independently associated with CAB and predicted a poorer functional outcome among IS and TIA patients. CLINICAL RELEVANCE: Clinical assessment of tooth loss may provide important information on risk for CAB and poorer functional outcome among stroke patients.

Charcoal-based mouthwashes: a literature review.

The commercial marketplace has seen a rapid increase in the number of over-the-counter charcoal-containing mouthwashes. The purpose of this systemic review was to examine the clinical and laboratory evidence supporting therapeutic claims of efficacy and safety of use of charcoal-based mouthwashes. Secondly, the product labels and information of 36 commercially marketed charcoal mouthwashes were reviewed for active ingredients. Only 8% of charcoal mouthwashes contained an active ingredient, such as cetylpyridinium chloride or chlorhexidine. There is insufficient evidence to substantiate the therapeutic and cosmetic marketing claims of charcoal-based mouthwashes, including antimicrobial activity, anti-halitosis, tooth whitening, periodontal disease control, caries reduction and tooth remineralisation, among others. Moreover, there is no available information on charcoal particulate size or abrasivity of any of these products. Dental clinicians should advise their patients to exercise caution when using over-the-counter charcoal-containing mouthwashes because of the lack of evidence supporting therapeutic or cosmetic effectiveness as well as safety.

Changes in Peri-implant Soft Tissue Thickness with Bone Grafting and Dermis Allograft. Part II: A Comparative Retrospective Case Series Using a Subcrestal Angle Correction Implant Design.

Immediate tooth replacement therapy (ITRT) in the maxillary anterior sextant is an increasingly frequent treatment option sought by patients and performed by clinicians worldwide. Achieving long-term results that are predictable, stable, esthetic, and healthy is the ultimate goal. This trend also lends itself to minimally invasive surgery as well as defining the procedure to a singular surgical intervention. Preserving and augmenting hard and soft tissues at the time of immediate implant placement provides the best opportunity to achieve these goals. Incorporating an implant with a subcrestal angle correction [SAC] or biaxial feature facilitates screw-retention of both provisional and definitive restorations through the cingulum portion of the crown. Compared to uniaxial implants, these implants also feature an extended or variable platform switch [VPS] facially. Measurements of the peri-implant soft tissue thickness 2.0 mm apical to the facial free gingival margin were compared between two groups of 15 consecutively treated patients with different implant designs to evaluate the effect of SAC/VPS for ITRT. The null hypothesis was that there is no difference between uniaxial and biaxial implants with bone grafting and dermis allograft. These authors contend that using a combined hard and soft tissue grafting approach along with SAC/VPS biaxial implants has a synergistic effect on increasing peri-implant soft tissue thickness compared to uniaxial implants.

Periodontal Pathogens and Neuropsychiatric Health.

Increasing evidence incriminates low-grade inflammation in cardiovascular, metabolic diseases, and neuropsychiatric clinical conditions, all important causes of morbidity and mortality. One of the upstream and modifiable precipitants and perpetrators of inflammation is chronic periodontitis, a polymicrobial infection with Porphyromonas gingivalis (P. gingivalis) playing a central role in the disease pathogenesis. We review the association between P. gingivalis and cardiovascular, metabolic, and neuropsychiatric illness, and the molecular mechanisms potentially implicated in immune upregulation as well as downregulation induced by the pathogen. In addition to inflammation, translocation of the pathogens to the coronary and peripheral arteries, including brain vasculature, and gut and liver vasculature has important pathophysiological consequences. Distant effects via translocation rely on virulence factors of P. gingivalis such as gingipains, on its synergistic interactions with other pathogens, and on its capability to manipulate the immune system via several mechanisms, including its capacity to induce production of immune-downregulating micro-RNAs. Possible targets for intervention and drug development to manage distal consequences of infection with P. gingivalis are also reviewed.

Survival of dental implants at sites after implant failure: A systematic review.

STATEMENT OF PROBLEM: Despite an overall high survival rate for dental implants, the effectiveness of implant retreatment remains unclear. PURPOSE: The purpose of this systematic review was to examine the survival rate of implants placed at sites which had an implant failure and to investigate factors that might affect outcomes after retreatment. MATERIAL AND METHODS: A search of electronic databases limited to English language articles was conducted using the following MeSH terms: "dental implants," "dental implantation," or "dental restoration failure," combined with "retreatment," "replacement," or "reoperation." A hand search of selected journals was also performed. Of the retrieved 668 publications, 8 retrospective clinical studies met the inclusion criteria, providing the survival outcome for 673 implants in 557 patients after retreatment. Implant- and patient-related characteristics related to implant failures were assessed. RESULTS: The weighted mean survival rate for implants after retreatment was 86.3%, with follow-up ranging from less than 1 year to over 5 years. The survival rates of smooth-surfaced and rough-surfaced implants were compared in 217 retreated implants, revealing a significantly higher survival rate for rough-surfaced implants than for smooth-surfaced implants (90% versus 68.7%). Insufficient data were available to evaluate the effect of patient- or treatment-related characteristics on the survival of implants after retreatment. CONCLUSIONS: The survival rate of retreated implants is lower than that generally reported after initial implant placement. Higher survival rates were reported with rough-surfaced implants than with smooth-surfaced implants in retreatment. An overall implant survival rate of 86.3% after retreatment suggests that most initial implant failures are likely attributable to modifiable risk factors, such as implant architecture, anatomic site, infection, and occlusal overload.

Iron oxide nanoparticle-calcium phosphate cement enhanced the osteogenic activities of stem cells through WNT/ß-catenin signaling.

Calcium phosphate cement (CPC), functionalized with iron oxide nanoparticles (IONP), is of great promise to promote osteoinduction and new bone formation. In this work, the IONP powder was added into the CPC powder to fabricate CPC + IONP scaffolds and the effects of the novel composite on bone matrix formation and osteogenesis of human dental pulp stem cells (hDPSCs) were explored. A series of CPC + IONP magnetic scaffolds with different IONP contents (1%, 3% and 6%) were fabricated using 5% chitosan solution as the cement liquid. Western blotting and RT-PCR were used to analyze the signaling pathway. The IONP incorporation substantially enhanced the performance of CPC + IONP, with increases in both mechanical strength and cellular activities. The IONP addition greatly promoted the osteogenesis of hDPSCs, elevating the ALP activity, the expression of osteogenic marker genes and bone matrix formation with 1.5-2-fold increases. The 3% IONP incorporation showed the most enhancement among all groups. Activation of the extracellular signal-related kinases WNT/ß-catenin in DPSCs was observed, and this activation was attenuated by the WNT inhibitor DKK1. The results indicated that the osteogenic behavior of hDPSCs was likely driven by CPC + IONP via the WNT signaling pathway. In conclusion, incorporate IONP into CPC scaffold remarkably enhanced the spreading, osteogenic differentiation and bone mineral synthesis of stem cell. Therefore, this method had great potential for bone tissue engineering. The novel CPC + IONP composite scaffolds with stem cells are promising to provide an innovative strategy to enhance bone regenerative therapies.

Engineering of L-Plastin Peptide-Loaded Biodegradable Nanoparticles for Sustained Delivery and Suppression of Osteoclast Function In Vitro.

We have recently demonstrated that a small molecular weight amino-terminal peptide of L-plastin (10 amino acids; "MARGSVSDEE") suppressed the phosphorylation of endogenous L-plastin. Therefore, the formation of nascent sealing zones (NSZs) and bone resorption are reduced. The aim of this study was to develop a biodegradable and biocompatible PLGA nanocarrier that could be loaded with the L-plastin peptide of interest and determine the efficacy in vitro in osteoclast cultures. L-plastin MARGSVSDEE (P1) and scrambled control (P3) peptide-loaded PLGA-PEG nanoparticles (NP1 and NP3, respectively) were synthesized by double emulsion technique. The biological effect of nanoparticles on osteoclasts was evaluated by immunoprecipitation, immunoblotting, rhodamine-phalloidin staining of actin filaments, and pit forming assays. Physical characterization of well-dispersed NP1 and NP3 demonstrated ~130-150 nm size, < 0.07 polydispersity index, ~-3 mV ζ-potential, and a sustained release of the peptide for three weeks. Biological characterization in osteoclast cultures demonstrated the following: NP1 significantly reduced (a) endogenous L-plastin phosphorylation; (b) formation of NSZs and sealing rings; (c) resorption. However, the assembly of podosomes which are critical for cell adhesion was not affected. L-plastin peptide-loaded PLGA-PEG nanocarriers have promising potential for the treatment of diseases associated with bone loss. Future studies will use this sustained release of peptide strategy to systematically suppress osteoclast bone resorption activity in vivo in mouse models demonstrating bone loss.