Clinical Significance and Remaining Issues of Anti-HBc Antibody and HBV Core-Related Antigen.

Currently, hepatitis B virus (HBV) core antibody (anti-HBc antibody) and HBV core-related antigen (HBcrAg) are widely used as serum markers for diagnosis based on the HBV core region. This review focused on anti-HBc antibodies and HBcrAg and aimed to summarize the clinical significance of currently used assay systems and the issues involved. While anti-HBc is very significant for clinical diagnosis, the clinical significance of quantitative assay of anti-HBc antibody has been reevaluated with improvements in diagnostic performance, including its association with clinical stage and prediction of carcinogenesis and reactivation. In addition, concerning the new HBcrAg, a high-sensitivity assay method has recently been established, and its diagnostic significance, including the prediction of reactivation, is being reevaluated. On the other hand, the quantitative level of anti-HBc antibody expressed in different units among assay systems complicates the interpretation of the results. However, it is difficult to standardize assay systems as they vary in advantages, and caution is needed in interpreting the assay results. In conclusion, with the development of highly sensitive HBcrAg and anti-HBc antibody, a rapid and sensitive detection assay system has been developed and used in clinical practice. In the future, it is hoped that a global standard will be created based on the many clinical findings.

Achieving Complete Human Gingival Fibroblast Collagen Coverage on Implant Abutments through Vacuum Ultraviolet (VUV) Photofunctionalization.

PURPOSE: The formation of a biological seal between implant abutments and the surrounding soft tissue is a preventive strategy against peri-implantitis. The aim of this study is to test the hypothesis that surfaces of prosthetic implant abutments treated with vacuum ultraviolet (VUV) light enhance the growth and function of human gingival fibroblasts. MATERIALS AND METHODS: Implant abutments were treated with 172 nm VUV light for one minute. Untreated abutments were subjected as controls. Their surface properties were characterized using SEM, contact angle measurements, and chemical composition analysis. Human gingival fibroblasts were cultured on both untreated and VUV-treated abutments to evaluate cell attachment, proliferation, distribution, and collagen production. Cell detachment assays were also performed under various mechanical and chemical stimuli. RESULTS: After VUV treatment, implant abutments demonstrated a notable transition from hydrophobic to hydrophilic wettability. Surface element analysis revealed a considerable reduction in surface carbon and increases in oxygen and titanium elements on the VUV-treated surfaces. On day 1 of culture, 3.9 times more fibroblasts attached on VUV-treated abutments than on untreated control abutments. Fibroblastic proliferation increased 1.9-3.1 times on VUV-treated abutments, along with a significant improvement in the distribution of populating cells. Collagen production on VUV-treated abutments increased by 1.5-1.7 times. While untreated abutment surfaces showed voids and limited spread of collagen deposition, dense and full coverage of collagen was observed on VUV-treated abutments, with a great contrast in the challenging axial surface zone. Cell retention against mechanical and chemical detaching stimuli was increased 11.3 and 4.3 times, respectively, by VUV treatment. CONCLUSION: Treatment of implant abutments with VUV light for one minute resulted in a reduction of surface carbon and a transformation of the surface from hydrophobic to hydrophilic. This led to enhanced attachment, proliferation, and retention of human gingival fibroblasts, along with nearly complete collagen coverage on implant abutments. These in vitro results indicate the promising potential of utilizing VUV photofunctionalized implant abutments to enhance soft tissue reaction and sealing mechanisms.

Octacalcium phosphate collagen composite for periodontal regeneration in a canine one-wall intrabony defect.

OBJECTIVE: This study aimed to evaluate the regenerative capacities of octacalcium phosphate collagen composite (OCP/Col) in one-wall intrabony defects in dogs. The background data discuss the present state of the field: No study has assessed the efficacy of OCP/Col for periodontal regeneration therapy despite the fact that OCP/Col has proved to be efficient for bone regeneration. METHODS: In six beagle dogs, the mandibular left third premolars were extracted 12 weeks before the experimental surgery. Standardized bone defects (5 mm in height and 4 mm in width) were simulated on the distal surface of the second premolars and mesially on the fourth premolars. The defect was filled with either OCP/Col (experimental group) or left empty (control group). Histological and histomorphometric characteristics were compared 8 weeks after surgery. RESULTS: No infectious or ankylotic complications were detected at any of the tested sites. The experimental group exhibited a significantly greater volume, height, and area of newly formed bone than the control group. The former also showed a greater height of the newly formed cementum than the latter, although the results were not statistically significant. The newly formed periodontal ligaments were inserted into newly formed bone and cementum in the experimental group. CONCLUSION: OCP/Col demonstrated high efficacy for bone and periodontal tissue regeneration that can be successfully applied for one-wall intrabony defects.

Human Gingival Fibroblast Growth and Function in Response to Laser-Induced Meso-and Microscale Hybrid Topography on Dental Implant Healing Abutments.

PURPOSE: Laser-created titanium surface topographies enhance soft tissue attachment and implant stability. However, knowledge about the underlying mechanisms governing the tissue-level reaction is lacking. The objective of this study was to examine the behavior and function of human gingival fibroblasts growing on healing abutments with or without laser-textured topography. MATERIALS AND METHODS: Human primary gingival connective tissue fibroblasts were cultured on healing abutments with machined or laser-textured (Laser-Lok, BioHorizons) surfaces. Cellular and molecular responses were evaluated by cell density assay (WST-1), fluorescence microscopy, qRT-PCR, and detachment test. RESULTS: The machined surface showed mono-directional traces and scratches from milling, whereas the laser-textured surface showed a distinct morphology consisting of mono-directional meso-scale channels (15 µm pitch) and woven, oblique micro-ridges formed within the channel. There were no differences in initial fibroblast attachment, subsequent fibroblast proliferation, nor collagen production between the machined and laser-textured surfaces. Fibroblasts growing on laser-textured surface spread mono-directionally along the meso-channels, while cells growing on machined surfaces spread randomly. Fibroblasts on laser-textured surfaces were 1.8-times more resistant to detachment than those on machined surfaces. An adhesive glycoprotein (fibronectin) and trans-membrane adhesion linker gene (integrin beta-1) were upregulated on laser-textured surfaces. CONCLUSIONS: The increased fibroblast retention, uniform growth, increased transcription of cell adhesion proteins compellingly explain the enhanced tissue-level response to laser-created, hybrid textured titanium surfaces. These results provide a cellular and molecular rationale for the tissue reaction to this unique surface and support its extended use from implant fixtures and healing abutments to diverse prosthetic components where enhanced soft tissue responses would be desirable.

Vacuum Ultraviolet (VUV) Light Photofunctionalization to Induce Human Oral Fibroblast Transmigration on Zirconia.

Soft tissue adhesion and sealing around dental and maxillofacial implants, related prosthetic components, and crowns are a clinical imperative to prevent adverse outcomes of periodontitis and periimplantitis. Zirconia is often used to fabricate implant components and crowns. Here, we hypothesized that UV treatment of zirconia would induce unique behaviors in fibroblasts that favor the establishment of a soft tissue seal. Human oral fibroblasts were cultured on zirconia specimens to confluency before placing a second zirconia specimen (either untreated or treated with one minute of 172 nm vacuum UV (VUV) light) next to the first specimen separated by a gap of 150 µm. After seven days of culture, fibroblasts only transmigrated onto VUV-treated zirconia, forming a 2.36 mm volume zone and 5.30 mm leading edge. Cells migrating on VUV-treated zirconia were enlarged, with robust formation of multidirectional cytoplastic projections, even on day seven. Fibroblasts were also cultured on horizontally placed and 45° and 60° tilted zirconia specimens, with the latter configurations compromising initial attachment and proliferation. However, VUV treatment of zirconia mitigated the negative impact of tilting, with higher tilt angles increasing the difference in cellular behavior between control and VUV-treated specimens. Fibroblast size, perimeter, and diameter on day seven were greater than on day one exclusively on VUV-treated zirconia. VUV treatment reduced surface elemental carbon and induced superhydrophilicity, confirming the removal of the hydrocarbon pellicle. Similar effects of VUV treatment were observed on glazed zirconia specimens with silica surfaces. One-minute VUV photofunctionalization of zirconia and silica therefore promotes human oral fibroblast attachment and proliferation, especially under challenging culture conditions, and induces specimen-to-specimen transmigration and sustainable photofunctionalization for at least seven days.

Assessment of bone defect morphology for the adjunctive use of bone grafting combined with enamel matrix derivative: A 3-year cohort study.

BACKGROUND: There have been limited studies with statistically sufficient sample sizes for assessment of suitable bone defect morphology for combination therapy with enamel matrix derivative (EMD) and bone grafting. The aim of this study was to investigate the appropriate feature of intrabony defects, such as bone defect angle (DA) and the containment by bony wall, for yielding the additional benefit of bone grafting in combination with periodontal regenerative therapy using EMD. METHODS: Following periodontal regenerative therapy using EMD with or without autologous bone grafting, 282 intrabony defects of 177 participants were maintained for 3 years. Multilevel linear regression analysis was performed to evaluate the radiographic bony defect depth (RBD) reduction after adjusting for confounders. RESULTS: The baseline parameters, except for the proportion of contained bony defects and tooth mobility, did not differ significantly between the groups with and without bone grafts. There was no significant difference in the improvement of clinical parameters between the groups. The 1- and 3-year reduction of RBD showed significant inverse correlations with preoperative DA only in the group without bone graft. Furthermore, multivariate analysis showed a significant interaction between DA at baseline ≥40° and adjunctive bone grafting in the reduction of RBD, regardless of the number of bony walls. CONCLUSION: Adjunctive autologous bone grafting with enamel matrix derivative might be significantly beneficial for defect depth improvement in the case of DA at baseline ≥40°.

Genome-wide transcriptional responses of osteoblasts to different titanium surface topographies.

This is the first genome-wide transcriptional profiling study using RNA-sequencing to investigate osteoblast responses to different titanium surface topographies, specifically between machined, smooth and acid-etched, microrough surfaces. Rat femoral osteoblasts were cultured on machine-smooth and acid-etched microrough titanium disks. The culture system was validated through a series of assays confirming reduced osteoblast attachment, slower proliferation, and faster differentiation on microrough surfaces. RNA-sequencing analysis of osteoblasts at an early stage of culture revealed that gene expression was highly correlated (r = 0.975) between the two topographies, but 1.38 % genes were upregulated and 0.37 % were downregulated on microrough surfaces. Upregulated transcripts were enriched for immune system, plasma membrane, response to external stimulus, and positive regulation to stimulus processes. Structural mapping confirmed microrough surface-promoted gene sharing and networking in signaling pathways and immune system/responses. Target-specific pathway analysis revealed that Rho family G-protein signaling pathways and actin genes, responsible for the formation of stress fibers, cytoplasmic projections, and focal adhesion, were upregulated on microrough surfaces without upregulation of core genes triggered by cell-to-cell interactions. Furthermore, disulfide-linked or -targeted extracellular matrix (ECM) or membranous glycoproteins such as laminin, fibronectin, CD36, and thrombospondin were highly expressed on microrough surfaces. Finally, proliferating cell nuclear antigen (PCNA) and cyclin D1, whose co-expression reduces cell proliferation, were upregulated on microrough surfaces. Thus, osteoblasts on microrough surfaces were characterized by upregulation of genes related to a wide range of functions associated with the immune system, stress/stimulus responses, proliferation control, skeletal and cytoplasmic signaling, ECM-integrin receptor interactions, and ECM-membranous glycoprotein interactions, furthering our knowledge of the surface-dependent expression of osteoblastic biomarkers on titanium.

Influence of Surface Contaminants and Hydrocarbon Pellicle on the Results of Wettability Measurements of Titanium.

Hydrophilicity/hydrophobicity-or wettability-is a key surface characterization metric for titanium used in dental and orthopedic implants. However, the effects of hydrophilicity/hydrophobicity on biological capability remain uncertain, and the relationships between surface wettability and other surface parameters, such as topography and chemistry, are poorly understood. The objective of this study was to identify determinants of surface wettability of titanium and establish the reliability and validity of the assessment. Wettability was evaluated as the contact angle of ddH2O. The age of titanium specimens significantly affected the contact angle, with acid-etched, microrough titanium surfaces becoming superhydrophilic immediately after surface processing, hydrophobic after 7 days, and hydrorepellent after 90 days. Similar age-related loss of hydrophilicity was also confirmed on sandblasted supra-micron rough surfaces so, regardless of surface topography, titanium surfaces eventually become hydrophobic or hydrorepellent with time. On age-standardized titanium, surface roughness increased the contact angle and hydrophobicity. UV treatment of titanium regenerated the superhydrophilicity regardless of age or surface roughness, with rougher surfaces becoming more superhydrophilic than machined surfaces after UV treatment. Conditioning titanium surfaces by autoclaving increased the hydrophobicity of already-hydrophobic surfaces, whereas conditioning with 70% alcohol and hydrating with water or saline attenuated pre-existing hydrophobicity. Conversely, when titanium surfaces were superhydrophilic like UV-treated ones, autoclaving and alcohol cleaning turned the surfaces hydrorepellent and hydrophobic, respectively. UV treatment recovered hydrophilicity without exception. In conclusion, surface roughness accentuates existing wettability and can either increase or decrease the contact angle. Titanium must be age-standardized when evaluating surface wettability. Surface conditioning techniques significantly but unpredictably affect existing wettability. These implied that titanium wettability is significantly influenced by the hydrocarbon pellicle and other contaminants inevitably accumulated. UV treatment may be an effective strategy to standardize wettability by making all titanium surfaces superhydrophilic, thereby allowing the characterization of individual surface topography and chemistry parameters in future studies.

Histological diagnosis of polyploidy discriminates an aggressive subset of hepatocellular carcinomas with poor prognosis.

BACKGROUND: Although genome duplication, or polyploidization, is believed to drive cancer evolution and affect tumor features, its significance in hepatocellular carcinoma (HCC) is unclear. We aimed to determine the characteristics of polyploid HCCs by evaluating chromosome duplication and to discover surrogate markers to discriminate polyploid HCCs. METHODS: The ploidy in human HCC was assessed by fluorescence in situ hybridization for multiple chromosomes. Clinicopathological and expression features were compared between polyploid and near-diploid HCCs. Markers indicating polyploid HCC were explored by transcriptome analysis of cultured HCC cells. RESULTS: Polyploidy was detected in 36% (20/56) of HCCs and discriminated an aggressive subset of HCC that typically showed high serum alpha-fetoprotein, poor differentiation, and poor prognosis compared to near-diploid HCCs. Molecular subtyping revealed that polyploid HCCs highly expressed alpha-fetoprotein but did not necessarily show progenitor features. Histological examination revealed abundant polyploid giant cancer cells (PGCCs) with a distinct appearance and frequent macrotrabecular-massive architecture in polyploid HCCs. Notably, the abundance of PGCCs and overexpression of ubiquitin-conjugating enzymes 2C indicated polyploidy in HCC and efficiently predicted poor prognosis in combination. CONCLUSIONS: Histological diagnosis of polyploidy using surrogate markers discriminates an aggressive subset of HCC, apart from known HCC subgroups, and predict poor prognosis in HCC.

Nitric oxide synthase contributes to the maintenance of LTP in the oxytocin-mRFP1 neuron of the rat hypothalamus.

Oxytocin (OXT) is a neuropeptide hormone that plays a critical role in nociception. Long-term potentiation (LTP) is a major form of synaptic plasticity in the central nervous system. Recently, LTP has been reported in the hypothalamus; however, data on LTP in hypothalamic OXT-ergic neurons are unclear. Furthermore, the signaling pathways for hypothalamic OXT-ergic neuronal LTP and its physiological significance remain unknown. Herein, we aimed to investigate the induction of hypothalamic OXT-ergic neuronal LTP and its synaptic mechanism using OXT-monomeric red fluorescent protein 1 transgenic rats to visualize and record from OXT-ergic neurons. The hypothalamic paraventricular nucleus (PVN) OXT-ergic neuronal LTP induced by the pairing protocol was dependent on N-methyl-D-aspartate receptor (NMDAR). Furthermore, nitric oxide synthase (NOS) is required to maintain the LTP regardless of the NMDARs. In addition, hypothalamic OXT-ergic neuronal LTP was not induced in the adjuvant arthritis rat model but increased excitatory postsynaptic currents were detected. LTP in hypothalamic OXT-ergic neurons in the PVN in the presence of NOS may be involved in neuronal changes during OXT synthesis in chronic inflammation.

Chemogenetic Activation of Oxytocin Neurons Improves Pain in a Reserpine-induced Fibromyalgia Rat Model.

Fibromyalgia (FM) is a syndrome characterized by chronic pain with depression as a frequent comorbidity. However, efficient management of the pain and depressive symptoms of FM is lacking. Given that endogenous oxytocin (OXT) contributes to the regulation of pain and depressive disorders, herein, we investigated the role of OXT in an experimental reserpine-induced FM model. In FM model, OXT-monomeric red fluorescent protein 1 (OXT-mRFP1) transgenic rats exhibited increased depressive behavior and sensitivity in a mechanical nociceptive test, suggesting reduced pain tolerance. Additionally, the development of the FM-like phenotype in OXT-mRFP1 FM model rats was accompanied by a significant reduction in OXT mRNA expression in the magnocellular neurons of the paraventricular nucleus. OXT-mRFP1 FM model rats also had significantly fewer tryptophan hydroxylase (TPH)- and tyrosine hydroxylase (TH)-immunoreactive (ir) neurons as well as reduced serotonin and norepinephrine levels in the dorsal raphe and locus coeruleus. To investigate the effects of stimulating the endogenous OXT pathway, rats expressing OXT-human muscarinic acetylcholine receptor (hM3Dq)-mCherry designer receptors exclusively activated by designer drugs (DREADDs) were also assessed in the FM model. Treatment of these rats with clozapine-N-oxide (CNO), an hM3Dq-activating drug, significantly improved characteristic FM model-induced pathophysiological pain, but did not alter depressive-like behavior. The chemogenetically induced effects were reversed by pre-treatment with an OXT receptor antagonist, confirming the specificity of action via the OXT pathway. These results indicate that endogenous OXT may have analgesic effects in FM, and could be a potential target for effective pain management strategies for this disorder.

Factors associated with the response to atezolizumab/bevacizumab combination therapy for hepatocellular carcinoma.

Background and Aim: The purpose of this study was to analyze factors associated with the overall survival (OS) of atezolizumab/bevacizumab combination therapy for advanced hepatocellular carcinoma (aHCC). We also assessed the OS of patients with ineffective therapy and those who discontinued treatment owing to adverse events (AEs). Methods: This retrospective multicenter study involved 139 patients with aHCC who received atezolizumab/bevacizumab combination therapy between November 2020 and September 2022. Results: The median duration of treatment was 136.5 days, and the median observation period was 316 days. The overall response rate was 40%, and the disease control rate was 78% according to mRECIST criteria. Grade ≥2 AEs occurred in 63 patients (43%) and led to treatment discontinuation in 16 patients. Multivariate analysis revealed that treatment response and occurrence of grade ≥2 AEs after therapy, as well as low level of albumin-bilirubin (ALBI) grade and low level of des-gamma carboxy prothrombin (DCP) before therapy, were extracted as factors that contributed to OS. Log-rank tests with the Kaplan-Meier method showed significant differences in OS among these factors. The OS of patients who discontinued owing to AEs was significantly shorter than that of other patients. Conclusion: Not only factors before therapy but also treatment response and the appearance of AEs are involved in OS for atezolizumab/bevacizumab combination therapy. Although the development of AEs also contributed to OS, appropriate management of AEs is important to avoid discontinuing treatment with this combination.

Malnutrition- inflammation- atherosclerosis (MIA) syndrome associates with periodontitis in end-stage renal disease patients undergoing hemodialysis: a cross-sectional study.

Malnutrition-inflammation-atherosclerosis (MIA) syndrome is a significant risk factor for mortality in patients undergoing hemodialysis. This study aimed to investigate the association between MIA syndrome and oral health status in hemodialysis patients. A cross-sectional study was conducted on 254 hemodialysis patients. Comprehensive medical and dental examinations were performed. Three components were included to define MIA syndrome: Geriatric Nutritional Risk Index, serum high-sensitivity C-reactive protein, and history of cardiovascular events as indicators of malnutrition, inflammation, and atherosclerosis, respectively. The association of MIA syndrome components with periodontitis and occlusal support was examined by multiple-ordered logistic regression analysis. Of 254 participants, 188 (74.0%) had at least one component of MIA syndrome. After adjusting for possible confounding factors, severe periodontitis was significantly associated with presence of more components of MIA syndrome (odds ratio [OR]: 2.64, 95% confidence interval [CI], 1.44-4.84, p = 0.002) and inflammation and malnutrition components (OR: 2.47 and 3.46, 95% CI 1.16-5.28 and 1.70-7.05, p = 0.020 and 0.001). On the other hand, occlusal support, evaluated by Eichner index, was not significantly associated with MIA syndrome or any of its components. In conclusion, periodontitis is associated with MIA syndrome, particularly with inflammation and malnutrition in hemodialysis patients, independent of occlusal support.

Conditional Mitigation of Dental-Composite Material-Induced Cytotoxicity by Increasing the Cure Time.

Light-cured composite resins are widely used in dental restorations to fill cavities and fabricate temporary crowns. After curing, the residual monomer is a known to be cytotoxic, but increasing the curing time should improve biocompatibility. However, a biologically optimized cure time has not been determined through systematic experimentation. The objective of this study was to examine the behavior and function of human gingival fibroblasts cultured with flowable and bulk-fill composites cured for different periods of time, while considering the physical location of the cells with regard to the materials. Biological effects were separately evaluated for cells in direct contact with, and in close proximity to, the two composite materials. Curing time varied from the recommended 20 s to 40, 60, and 80 s. Pre-cured, milled-acrylic resin was used as a control. No cell survived and attached to or around the flowable composite, regardless of curing time. Some cells survived and attached close to (but not on) the bulk-fill composite, with survival increasing with a longer curing time, albeit to <20% of the numbers growing on milled acrylic even after 80 s of curing. A few cells (<5% of milled acrylic) survived and attached around the flowable composite after removal of the surface layer, but attachment was not cure-time dependent. Removing the surface layer increased cell survival and attachment around the bulk-fill composite after a 20-s cure, but survival was reduced after an 80-s cure. Dental-composite materials are lethal to contacting fibroblasts, regardless of curing time. However, longer curing times mitigated material cytotoxicity exclusively for bulk-fill composites when the cells were not in direct contact. Removing the surface layer slightly improved biocompatibility for cells in proximity to the materials, but not in proportion to cure time. In conclusion, mitigating the cytotoxicity of composite materials by increasing cure time is conditional on the physical location of cells, the type of material, and the finish of the surface layer. This study provides valuable information for clinical decision making and novel insights into the polymerization behavior of composite materials.

A Novel High-Energy Vacuum Ultraviolet Light Photofunctionalization Approach for Decomposing Organic Molecules around Titanium.

Titanium undergoes biological aging, represented by increased hydrophobicity and surface accumulation of organic molecules over time, which compromises the osseointegration of dental and orthopedic implants. Here, we evaluated the efficacy of a novel UV light source, 172 nm wavelength vacuum UV (VUV), in decomposing organic molecules around titanium. Methylene blue solution used as a model organic molecule placed in a quartz ampoule with and without titanium specimens was treated with four different UV light sources: (i) ultraviolet C (UVC), (ii) high-energy UVC (HUVC), (iii) proprietary UV (PUV), and (iv) VUV. After one minute of treatment, VUV decomposed over 90% of methylene blue, while there was 3-, 3-, and 8-fold more methylene blue after the HUVC, PUV, and UVC treatments, respectively. In dose-dependency experiments, maximal methylene blue decomposition occurred after one minute of VUV treatment and after 20-30 min of UVC treatment. Rapid and effective VUV-mediated organic decomposition was not influenced by the surface topography of titanium or its alloy and even occurred in the absence of titanium, indicating only a minimal photocatalytic contribution of titanium dioxide to organic decomposition. VUV-mediated but not other light source-mediated methylene blue decomposition was proportional to its concentration. Plastic tubes significantly reduced methylene blue decomposition for all light sources. These results suggest that VUV, in synergy with quartz ampoules, mediates rapid and effective organic decomposition compared with other UV sources. This proof-of-concept study paves the way for rapid and effective VUV-powered photofunctionalization of titanium to overcome biological aging.

Preclinical evaluation of the effect of periodontal regeneration by carbonate apatite in a canine one-wall intrabony defect model.

Objective: This study aimed to histologically compare periodontal regeneration of one-wall intrabony defects treated with open flap debridement, ß-tricalcium phosphate (ß-TCP), and carbonate apatite (CO3Ap) in dogs. Methods: The mandibular third premolars of four beagle dogs were extracted. Twelve weeks after the extraction, a one-wall bone defect of 4 mm × 5 mm (mesio-distal width × depth) was created on the distal side of the mandibular second premolar and mesial side of the fourth premolar. Each defect was randomly allocated to open flap debridement (control group), periodontal regeneration utilizing ß-TCP, or CO3Ap. Eight weeks after the surgery, histologic and histometric analyses were performed. Results: No ankylosis, infection, or acute inflammation was observed at any of the experimental sites. Newly formed bone and cementum were observed in all experimental groups. The mineral apposition rate of the alveolar bone crest was higher in the CO3Ap group than in the control and ß-TCP groups. The ratio of the new bone area was significantly higher in the CO3Ap group than in the control group (P < 0.05). The bone contact percentage of the residual granules was significantly higher in the CO3Ap group than in the ß-TCP group (P < 0.05). Conclusion: Although this study has limitations, the findings revealed the safety and efficacy of CO3Ap for periodontal regeneration in one-wall intrabony defects in dogs, and CO3Ap has a better ability to integrate with bone than ß-TCP.

Impact of nano-scale trabecula size on osteoblastic behavior and function in a meso-nano hybrid rough biomimetic zirconia model.

PURPOSE: A novel implant model consisting of meso-scale cactus-inspired spikes and nano-scale bone-inspired trabeculae was recently developed to optimize meso-scale roughness on zirconia. In this model, the meso-spike dimension had a significant impact on osteoblast function. To explore how different nano-textures impact this model, here we examined the effect of different nano-trabecula sizes on osteoblast function while maintaining the same meso-spike conformation. METHODS: Zirconia disks with meso-nano hybrid surfaces were created by laser etching. The meso-spikes were fixed to 40 µm high, whereas the nano-texture was etched as large and small trabeculae of average Feret diameter 237.0 and 134.1 nm, respectively. A polished surface was also prepared. Rat bone marrow-derived and human mesenchymal stromal cell-induced osteoblasts were cultured on these disks. RESULTS: Hybrid rough surfaces, regardless of nano-trabecula dimension, robustly promoted the osteoblastic differentiation of both rat and human osteoblasts compared to those on polished surfaces. Hybrid surfaces with small nano-trabeculae further enhanced osteoblastic differentiation compared with large nano-trabeculae. However, the difference in osteoblastic differentiation between small and large nano-trabeculae was much smaller than the difference between the polished and hybrid rough surfaces. The nano-trabecula size did not influence osteoblast attachment and proliferation, or protein adsorption. Both hybrid surfaces were hydro-repellent. The atomic percentage of surface carbon was lower on the hybrid surface with small nano-trabeculae. CONCLUSIONS: Small nano-trabeculae promoted osteoblastic differentiation more than large nano-trabeculae when combined with meso-scale spikes. However, the biological impact of different nano-trabeculae was relatively small compared with that of different dimensions of meso-spikes.

Income-related inequalities in the association of smoking with periodontitis: a cross-sectional analysis in Tokyo Metropolitan Districts.

OBJECTIVE: Socio-economic status (SES) and smoking are risk factors for periodontitis; however, their interaction has not been determined. We investigated the effect of modification of SES and smoking with periodontal conditions. MATERIALS AND METHODS: Data on the social background, smoking status, and dental examination of 1033 individuals residing in the Tokyo Metropolitan District were analyzed. The outcomes were the number of remaining teeth and the proportion of teeth with probing pocket depth (PPD) ≥ 4 mm and ≥ 6 mm. Multilevel linear and Poisson regression analyses were performed after adjusting for possible confounding factors, including SES, assessed by the average income of the residential area. RESULTS: The mean number of remaining teeth was 24.6 ± 4.8, and the proportion of teeth with PPD ≥ 4 mm and ≥ 6 mm was 31.2 ± 28.5% and 12.2 ± 18.1%, respectively. After adjusting for confounding factors, the lowest-income population had significantly lesser teeth (coefficient: - 0.46, 95% CI - 0.89, 0.02, p = 0.039) and a higher proportion of teeth with PPD ≥ 4 mm than the highest-income population (ratio of means: 1.22, 95% CI 1.03-1.44, p = 0.013). Significant interactions were observed; income inequalities in periodontitis were significant only among current smokers. CONCLUSION: Inequality in socio-economic status is associated with oral health inequalities. The adverse effects of smoking on periodontitis might be greater in the low-income population. CLINICAL RELEVANCE: The low-income population, especially current smokers, had significantly more compromised oral health than the high-income population. In addition to the emphasis on smoking cessation, the promotion of universal health coverage for dental care is necessary to reduce oral health inequalities.

Disparity in the Influence of Implant Provisional Materials on Human Gingival Fibroblasts with Different Phases of Cell Settlement: An In Vitro Study.

The development of healthy peri-implant soft tissues is critical to achieving the esthetic and biological success of implant restorations throughout all stages of healing and tissue maturation, starting with provisionalization. The purpose of this study was to investigate the effects of eight different implant provisional materials on human gingival fibroblasts at various stages of cell settlement by examining initial cell attachment, growth, and function. Eight different specimens-bis-acrylic 1 and 2, flowable and bulk-fill composites, self-curing acrylic 1 and 2, milled acrylic, and titanium (Ti) alloy as a control-were fabricated in rectangular plates (n = 3). The condition of human gingival fibroblasts was divided into two groups: those in direct contact with test materials (contact experiment) and those in close proximity to test materials (proximity experiment). The proximity experiment was further divided into three phases: pre-settlement, early settlement, and late settlement. A cell culture insert containing each test plate was placed into a well where the cells were pre-cultured. The number of attached cells, cell proliferation, resistance to detachment, and collagen production were evaluated. In the contact experiment, bis-acrylics and composites showed detrimental effects on cells. The number of cells attached to milled acrylic and self-curing acrylic was relatively high, being approximately 70% and 20-30%, respectively, of that on Ti alloy. There was a significant difference between self-curing acrylic 1 and 2, even with the same curing modality. The cell retention ability also varied considerably among the materials. Although the detrimental effects were mitigated in the proximity experiment compared to the contact experiment, adverse effects on cell growth and collagen production remained significant during all phases of cell settlement for bis-acrylics and flowable composite. Specifically, the early settlement phase was not sufficient to significantly mitigate the material cytotoxicity. The flowable composite was consistently more cytotoxic than the bulk-fill composite. The harmful effects of the provisional materials on gingival fibroblasts vary considerably depending on the curing modality and compositions. Pre-settlement of cells mitigated the harmful effects, implying the susceptibility to material toxicity varies depending on the progress of wound healing and tissue condition. However, cell pre-settlement was not sufficient to fully restore the fibroblastic function to the normal level. Particularly, the adverse effects of bis-acrylics and flowable composite remained significant. Milled and self-curing acrylic exhibited excellent and acceptable biocompatibility, respectively, compared to other materials.