Journey of Mineral Precursors in Bone Mineralization: Evolution and Inspiration for Biomimetic Design.

Bone mineralization is a ubiquitous process among vertebrates that involves a dynamic physical/chemical interplay between the organic and inorganic components of bone tissues. It is now well documented that carbonated apatite, an inorganic component of bone, is proceeded through transient amorphous mineral precursors that transforms into the crystalline mineral phase. Here, the evolution on mineral precursors from their sources to the terminus in the bone mineralization process is reviewed. How organisms tightly control each step of mineralization to drive the formation, stabilization, and phase transformation of amorphous mineral precursors in the right place, at the right time, and rate are highlighted. The paradigm shifts in biomineralization and biomaterial design strategies are intertwined, which promotes breakthroughs in biomineralization-inspired material. The design principles and implementation methods of mineral precursor-based biomaterials in bone graft materials such as implant coatings, bone cements, hydrogels, and nanoparticles are detailed in the present manuscript. The biologically controlled mineralization mechanisms will hold promise for overcoming the barriers to the application of biomineralization-inspired biomaterials.

Evaluation of dentinal tubule occlusion and pulp tissue response after using 980-nm diode laser for dentin hypersensitivity treatment.

OBJECTIVES: To evaluate the effectiveness of the 980-nm diode laser for dentinal tubule occlusion, measure the intrapulpal temperature, and investigate the dental pulp response. MATERIALS AND METHODS: The dentinal samples were randomly divided into G1-G7 groups: control; 980-nm laser irradiation (0.5 W, 10 s; 0.5 W, 10 s × 2; 0.8 W, 10 s; 0.8 W, 10 s × 2; 1.0 W, 10 s; 1.0 W, 10 s × 2). The dentin discs were applied for laser irradiation and analyzed by scanning electron microscopy (SEM). The intrapulpal temperature was measured on the 1.0-mm and 2.0-mm thickness samples, and then divided into G2-G7 groups according to laser irradiation. Moreover, forty Sprague Dawley rats were randomly divided into the laser-irradiated group (euthanized at 1, 7, and 14 days after irradiation) and the control group (non-irradiated). qRT-PCR, histomorphology, and immunohistochemistry analysis were employed to evaluate the response of dental pulp. RESULTS: SEM indicated the occluding ratio of dentinal tubules in the G5 (0.8 W, 10 s × 2) and G7 (1.0 W, 10 s × 2) were significantly higher than the other groups (p < 0.05). The maximum intrapulpal temperature rises in the G5 were lower than the standard line (5.5 ℃). qRT-PCR showed that the mRNA expression level of TNF-α and HSP-70 upregulated significantly at 1 day (p < 0.05). Histomorphology and immunohistochemistry analysis showed that, compared with the control group, the inflammatory reaction was slightly higher at the 1 and 7 days (p < 0.05) and decreased to the normal levels at 14 days (p > 0.05). CONCLUSIONS: A 980-nm laser at a power of 0.8 W with 10 s × 2 defines the best treatment for dentin hypersensitivity in terms of compromise between the efficacy of the treatment and the safety of the pulp. CLINICAL RELEVANCE: The 980-nm laser is an effective option for treating dentin sensitivity. However, we need to ensure the safety of the pulp during laser irradiation.

BMSC-Derived Exosomal CircHIPK3 Promotes Osteogenic Differentiation of MC3T3-E1 Cells via Mitophagy.

Exosome-based therapy is emerging as a promising strategy to promote bone regeneration due to exosomal bioactive cargos, among which circular RNA (circRNA) has recently been recognized as the key effector. The role of exosomal circRNA derived from bone marrow mesenchymal stem cells (BMSCs) has not been well-defined. The present study aimed to clarify the regulatory function and molecular mechanism of BMSC-derived exosomal circRNA in osteogenesis. Exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) were isolated and identified. BMSC-Exos' pro-osteogenic effect on MC3T3-E1 cells was validated by alkaline phosphatase (ALP) activity and Alizarin Red staining. Through bioinformatic analysis and molecular experiments, circHIPK3 was selected and verified as the key circRNA of BMSC-Exos to promote osteoblast differentiation of MC3T3-E1 cells. Mechanistically, circHIPK3 acted as an miR-29a-5p sponge and functioned in mitophagy via targeting miR-29a-5p and PINK1. Additionally, we showed that the mitophagy level of MC3T3-E1 cells were mediated by BMSC-Exos, which promoted the osteogenic differentiation. Collectively, our results revealed an important role for BMSC-derived exosomal circHIPK3 in osteogenesis. These findings provide a potentially effective therapeutic strategy for bone regeneration.

COPI Vesicle Disruption Inhibits Mineralization via mTORC1-Mediated Autophagy.

Bone mineralization is a sophisticated regulated process composed of crystalline calcium phosphate and collagen fibril. Autophagy, an evolutionarily conserved degradation system, whereby double-membrane vesicles deliver intracellular macromolecules and organelles to lysosomes for degradation, has recently been shown to play an essential role in mineralization. However, the formation of autophagosomes in mineralization remains to be determined. Here, we show that Coat Protein Complex I (COPI), responsible for Golgi-to-ER transport, plays a pivotal role in autophagosome formation in mineralization. COPI vesicles were increased after osteoinduction, and COPI vesicle disruption impaired osteogenesis. Mechanistically, COPI regulates autophagy activity via the mTOR complex 1 (mTORC1) pathway, a key regulator of autophagy. Inhibition of mTOR1 rescues the impaired osteogenesis by activating autophagy. Collectively, our study highlights the functional importance of COPI in mineralization and identifies COPI as a potential therapeutic target for treating bone-related diseases.

Mesenchymal stem cell-derived extracellular vesicles for treatment of bone loss within periodontitis in pre-clinical animal models: a meta-analysis.

BACKGROUND: Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) represent an effective and promising strategy for periodontitis, although studies remain pre-clinical. Herein, a meta-analysis was conducted to assess the efficacy of MSC-EVs in animal models of periodontitis. METHODS: The PubMed, Web of Science, and Embase electronic databases were searched up to Dec 2022 to retrieve preclinical studies examining the use of MSC-EVs for periodontitis treatment. Meta-analyses and sub-group analyses were performed to assess the effect of MSC-EVs on Bone Volume/Total Volume (BV/TV) or the distance between the cementoenamel junction and alveolar bone crest (CEJ-ABC) in pre-clinical animal models of periodontitis. RESULTS: 11 studies published from Mar 2019 to Oct 2022 met the inclusion criteria. Overall, MSC-EVs contributed to periodontal bone regeneration in the inflammatory bone loss area due to periodontitis, as represented by a weighted mean difference (WMD) of 14.07% (95% CI = 6.73, 21.41%, p < 0.001) for BV/TV and a WMD of -0.12 mm (95% CI= -0.14, -0.11 mm, p < 0.001) for CEJ-ABC. However, sub-analysis suggested that there was no significant difference in CEJ-ABC between studies with bioactive scaffolds and studies without bioactive scaffolds (p = 0.60). CONCLUSIONS: The present study suggests that MSC-EVs may represent an attractive therapy for the treatment of inflammatory bone loss within periodontitis.

Clinical effectiveness of adjunctive diode laser on scaling and root planing in the treatment of periodontitis: is there an optimal combination of usage mode and application regimen? A systematic review and meta-analysis.

This review aims to evaluate the adjunctive clinical effectiveness of diode laser (DL) to scaling and root planing (SRP) in the treatment of periodontitis, and identify the optimal combination of usage mode and application regimen of DL. Eight electronic databases were searched up to January 2021. Probing pocket depth (PPD), clinical attachment loss (CAL), bleeding on probing (BOP), plaque index (PI), and gingival index (GI) were assessed at short-term (4-6 weeks), 3-month, and 6-month follow-ups. Based on DL usage mode, studies were divided into three groups: inside, outside pocket, and combined modes. As for application regimen, studies in each group were further subdivided into single- and multiple-session subgroups. Thirty randomized controlled trials with 825 participants were included. For inside mode, single-session DL showed significant improvements for PPD (short-term, and 3-month, p < 0.05), CAL (short-term, and 3-month, p < 0.05), PI (3- and 6-month, p < 0.05), and GI (short-term, 3-month, and 6-month, p < 0.05). For outside mode, multiple-session DL showed notable improvements for most clinical outcomes (p < 0.05). The effect of combined mode was still uncertain. Adjunctive DL had additional clinical benefits in the treatment of periodontitis. One session laser treatment is suggested when DL is applied inside pocket in future clinical practice. Meanwhile, more than one session laser treatment presents better outcomes when DL is used outside pocket. PROSPERO: CRD42020156162.

PINK1 mediated mitophagy attenuates early apoptosis of gingival epithelial cells induced by high glucose.

BACKGROUND: Oxidative stress mediated by hyperglycemia damages cell-reparative processes such as mitophagy. Down-regulation of mitophagy is considered to be a susceptible factor for diabetes mellitus (DM) and its complications. However, the role of mitophagy in DM-associated periodontitis has not been fully elucidated. Apoptosis of human gingival epithelial cells (hGECs) is one of the representative events of DM-associated periodontitis. Thus, this study aimed to investigate PTEN-induced putative kinase 1 (PINK1)-mediated mitophagy activated in the process of high glucose (HG)-induced hGECs apoptosis. METHODS: For dose-response studies, hGECs were incubated in different concentrations of glucose (5.5, 15, 25, and 50 mmol/L) for 48 h. Then, hGECs were challenged with 25 mmol/L glucose for 12 h and 48 h, respectively. Apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL), caspase 9 and mitochondrial membrane potential (MMP). Subsequently, autophagy was evaluated by estimating P62, LC3 II mRNA levels, LC3 fluorescent puncta and LC3-II/I ratio. Meanwhile, the involvement of PINK1-mediated mitophagy was assessed by qRT-PCR, western blotting and immunofluorescence. Finally, hGECs were transfected with shPINK1 and analyzed by MMP, caspase 9 and annexin V-FITC apoptosis. RESULTS: The number of TUNEL-positive cells and caspase 9 protein were significantly increased in cells challenged with HG (25 mmol/L) for 48 h (HG 48 h). MMP was impaired both at HG 12 h and HG 48 h, but the degree of depolarization was more serious at HG 48 h. The autophagy improved as the amount of LC3 II increased and p62 decreased in HG 12 h. During this process, HG 12 h treatment induced PINK1-mediated mitophagy. PINK1 silencing with HG 12 h resulted in MMP depolarization and cell apoptosis. CONCLUSIONS: These results suggested that loss of the PINK1 gene may cause mitochondrial dysfunction and increase sensitivity to HG-induced apoptosis of hGECs at the early stage. PINK1 mediated mitophagy attenuates early apoptosis of gingival epithelial cells induced by high glucose.

Anti-Sandwich Structured Photo-Electronic Wound Dressing for Highly Efficient Bacterial Infection Therapy.

Photo-electronic devices based on reactive oxygen species (ROS) generation suffer a crucial limitation in wound treatment due to their sandwich structure, which prevents the contact of ROS with wound tissue. In this work, the first anti-sandwich structured visible-light/electricity dual-responsive wound dressing is constructed for treatment of methicillin-resistant Staphylococcus aureus (MRSA), based on selenoviologen-appendant polythiophene (SeV2+ -PT)-containing polyacrylamide hydrogels. The new wound dressing is named an anti-sandwich structured photo-electronic wound dressing (PEWD). The unique structure of PEWD enables its use in synergistic electrodynamic and photodynamic therapy (EDT and PDT), providing rapid, on-demand, and sustained generation of ROS in situ via short-time light irradiation and/or wireless-controlled electrification. The PEWD possesses good flexibility, excellent biocompatibility, and fast response, as well as sustained ROS generation in a physiological environment. Animal experiments demonstrate effective ROS generation in 6 s under irradiation and electrification, inhibiting infection at an early stage, and substantially shortening the healing time of bacterial infection (to within 7 days). This proof-of-concept research holds great promise in developing new flexible PEWD, and novel strategies to improve wound treatment.

Comparison of crown fit and operator preferences between tooth preparation with electric and air-turbine handpieces.

STATEMENT OF PROBLEM: Tooth preparations for ceramic crowns require precision and accuracy, which may be influenced by the choice of dental handpiece. However, comparisons of the accuracy of tooth preparations made with traditional air-turbine handpieces and electric handpieces are lacking. PURPOSE: The purpose of this in vitro study was to evaluate operator preferences and tooth preparation performance by using electric and air-turbine handpieces with self-reported preferences, sound levels, surface roughness, and the fit of the crown produced. MATERIAL AND METHODS: Twenty dentists were asked to use the air-turbine or the electric handpiece. Feedback on the noise, weight, feel of grip, flexibility, and tooth preparation in general was scored according to a visual analog scale (VAS). Additionally, the dentists were asked to complete a questionnaire on their handpiece preference. The noise of the 2 handpieces was measured by using a precision sound level meter. The surface roughness of 10 teeth was measured by using a profilometer. The other 18 teeth were prepared to measure the marginal and internal fit of ceramic crowns by the replica technique. The VAS scores of operator preferences were analyzed with the Wilcoxon signed ranks test. Decibel levels were analyzed with the Mann-Whitney U test. The McNemar test was used to compare the ratio of preferred handpiece. The surface roughness and marginal and internal fit were analyzed with the independent t test to determine significant differences (all α=.05). RESULTS: The electric handpiece was heavier, had a poorer grip feel, was less flexible (P<.001), produced lower noise and better feeling of the tooth preparation in general (P<.001), and was preferred in the finishing stage for its greater smoothness (P<.05). The noise produced by the electric handpiece was lower during both idling and tooth preparation at 15-cm, 30-cm, and 45-cm distances (P<.01). The electric handpiece produced surface roughness values (Sa) similar to those of the air-turbine handpiece (P>.05). No significant differences were noted for the marginal and internal crown fit between the air-turbine handpiece and electric handpiece groups (P>.05). CONCLUSIONS: Despite its heavier weight, poorer grip feel, and less flexibility, the electric handpiece emitted lower noise, produced better feeling of the tooth preparation in general, and was preferred in the finishing step of tooth preparation for its greater smoothness than the air-turbine handpiece. The surface roughness of the prepared teeth and the crown fit between the tooth and ceramic crown were not affected by the air-turbine or electric handpiece.

The therapeutic role of baicalein in combating experimental periodontitis with diabetes via Nrf2 antioxidant signaling pathway.

BACKGROUND AND OBJECTIVE: Oxidative stress has been suggested as an important pathogenic factor contributing to chronic periodontitis with diabetes mellitus (CPDM). Previous studies have revealed the potential therapeutic properties of baicalein (BCI) in oxidative stress-related diseases; however, the antioxidant effects of BCI on therapy for individual with CPDM remain largely unexplored. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in cellular defence against oxidative stress. In this study, we aim to determine whether BCI prevents diabetes-related periodontal tissue destruction by regulating Nrf2 signaling pathway. MATERIAL AND METHODS: Human gingival epithelial cells (hGECs) were challenged with high glucose (HG, 25 mmol/L) and/or lipopolysaccharide (LPS, 20 µg/mL). Reactive oxygen species (ROS) were detected by fluorescence-activated cell sorting. The changes of antioxidant-related genes, including Nrf2, catalase (Cat), glutamate-cysteine ligase catalytic subunit (Gclc), superoxide dismutase 1 (Sod1), and superoxide dismutase 2 (Sod2), were quantified by real-time PCR. The localization of phospho-Nrf2 (pNrf2, S40) in the nucleus was detected by immunofluorescence staining and laser scanning confocal microscope (LSCM). PNrf2 and total form of Nrf2 were determined using western blot. The above indicators together with mitochondrial membrane potential (MMP) were further investigated in hGECs pre-treated with different concentrations of BCI (0.01, 0.1, or 0.5 µg/mL) before stimulated with HG plus LPS (GP). Finally, the role of BCI in activating Nrf2 signaling pathway and relieving the alveolar bone absorption was examined in the CPDM model of Sprague Dawley rats. CPDM rats were oral gavaged with BCI (50, 100, or 200 mg/kg daily). The pNrf2 was detected by immunohistochemistry, and the alveolar bone absorption was examined by microcomputed tomography. RESULTS: Our results showed that ROS were significantly increased in both groups of HG and LPS, with the strongest generation in the GP group. In terms of ROS-related gene expression, we found that the mRNA levels of Nrf2, Cat, Gclc, Sod1, and Sod2 were significantly decreased in HG and LPS groups. In consistent with the strongest induction of ROS in GP group, the gene expression in GP group was further decreased as compared to those of HG and LPS groups. Also, the expression of pNrf2 exhibited the same trend with the expression of those antioxidant genes. However, the generation of ROS and the loss of mitochondrial membrane potential induced by GP were abolished by pre-treatment with different concentrations of BCI (0.01, 0.1, or 0.5 µg/mL). Interestingly, we observed that BCI promoted the nucleus translocation of pNrf2, as well as the gene expression levels of pNrf2 and its target genes (Cat, Gclc, Sod1, and Sod2). Finally, in the CPDM animal model, we found that BCI (at concentrations: 50, 100, and 200 mg/kg) markedly increased the number of pNrf2-positive cells in periodontal tissue and mitigated the alveolar bone loss. CONCLUSIONS: Our data revealed a potential role for clinic application of BCI under CPDM conditions, suggesting a new therapeutic drug for CPDM patients.

Cyclic compression emerged dual effects on the osteogenic and osteoclastic status of LPS-induced inflammatory human periodontal ligament cells according to loading force.

BACKGROUND: Appropriate mechanical stimulation is essential for bone homeostasis in healthy periodontal tissues. While the osteogenesis and osteoclast differentiation of inflammatory periodontal ligament cells under different dynamic loading has not been yet clear. The aim of this study is to clarify the inflammatory, osteogenic and pro-osteoclastic effects of different cyclic stress loading on the inflammatory human periodontal ligament cells (hPDLCs). METHODS: hPDLCs were isolated from healthy premolars and cultured in alpha minimum Eagle's medium (α-MEM). Lipopolysaccharides (LPS) were used to induce the inflammation state of hPDLCs in vitro. Determination of LPS concentration for the model of inflammatory periodontium was based on MTT and genes expression analysis. Then the cyclic stress of 0, 0-50, 0-90 and 0-150 kPa was applied to the inflammatory hPDLCs for 5 days respectively. mRNA and protein levels of osteogenic, osteoclastic and inflammation-related markers were examined after the treatment. RESULTS: MTT and RT-PCR results showed that 10 µg/ml LPS up-regulated TNF-α, IL-1ß, IL-6, IL-8 and MCP-1 mRNA levels (P < 0.05) and did not affect the cell viability (P > 0.05). The excessive loading of stress (150 kPa) with or without LPS strongly increased the expression of inflammatory-related markers TNF-α, IL-1ß, IL-6, IL-8, MCP-1 (P < 0.05) and osteoclastic markers RANKL, M-CSF, PTHLH and CTSK compared with other groups (P < 0.05), but had no significant effect on osteogenic genes. While 0-90 kPa cyclic pressure could up-regulate the expression of osteogenic genes ALP, COL-1, RUNX2, OCN, OPN and OSX in the healthy hPDLSCs. CONCLUSIONS: Collectively, it could be concluded that 0-150 kPa was an excessive stress loading which accelerated both inflammatory and osteoclastic effects, while 0-90 kPa may be a positive factor for the osteogenic differentiation of hPDLCs in vitro.

Does Probiotic Lactobacillus Have an Adjunctive Effect in the Nonsurgical Treatment of Peri-Implant Diseases? A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the additional effect of probiotic Lactobacillus in the nonsurgical management of peri-implant diseases (peri-implant mucositis and peri-implantitis). METHODS: Six databases were searched up to May 2019 without time and language restrictions. Study selection and data extraction were conducted independently by 2 reviewers. The inclusion criteria for this systematic review were defined based on the participants, intervention, comparison, outcomes, and study design (PICOS) format. Randomized controlled trials comparing nonsurgical treatment combined with probiotic Lactobacillus or placebo agent in patients with peri-implant diseases were included. The methodological quality of retrieved studies was assessed according to the Cochrane Collaboration's Risk of Bias tool, and the quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. Odds ratio and 95% confidence interval (CI) were used to describe dichotomous data, while mean difference and standardized mean difference with 95% CI were used to describe continuous variables. RESULTS: Seven randomized controlled trials with 296 implants were included in this meta-analysis. The mean difference of probing pocket depth (PPD) was -0.05 (95% CI: -0.28 to 0.18; P = .67) immediately after treatment termination and -0.17 (95% CI: -1.01 to 0.67, P = .69) at least 2 months after treatment termination. There was a slight reduction of PPD after treatment termination. Compared with placebo, Lactobacillus provided limited benefits in peri-implant mucositis. There were no significant differences in the secondary outcomes of bleeding on probing or plaque index (P > .05). In a narrative synthesis of peri-implantitis, the effect of Lactobacillus on PPD and bleeding on probing remained controversial. CONCLUSIONS: This systematic review and meta-analysis showed that probiotic Lactobacillus provide limited benefits to the nonsurgical treatment of peri-implant mucositis or peri-implantitis.

Influence of epigallocatechin-3-gallate in promoting proliferation and osteogenic differentiation of human periodontal ligament cells.

BACKGROUND: Epigallocatechin-3-gallate (EGCG) was recently proposed to have the potential to regulate bone metabolism, however, its influence on osteogenesis remains controversial. The present study aimed to investigate the effects of EGCG on the proliferation and osteogenesis of human periodontal ligament cells (hPDLCs). METHODS: Cells were cultured in osteogenic medium and treated with EGCG at various concentrations. Cell proliferation was analyzed using a CCK-8 assay and acridine orange (AO)/ethidium bromide (EB) staining. Flow cytometry was used to measure the intracellular reactive oxygen species (ROS) potential of hPDLCs. The expression levels of osteogenic marker genes and proteins in hPDLCs, including type I collagen (COL1), runt-related transcription factor 2 (RUNX2), osteopontin (OPN), and osterix (OSX), were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis. In addition, alkaline phosphatase (ALP) activity was monitored both quantitatively and qualitatively. Extracellular matrix mineralization was further analyzed by alizarin red S staining. RESULTS: The results showed that EGCG concentrations from 6 to 10 µM increased the ROS level and inhibited the cell proliferation of hPDLCs. EGCG concentrations from 2 to 8 µM effectively increased extracellular matrix mineralization, in which 4 and 6 µM EGCG generated the most mineralizing nodules. The ALP activity and the mRNA and protein expression levels of the tested osteogenic markers were most strongly up-regulated by treatment with 4 and 6 µM EGCG. CONCLUSIONS: The present study demonstrated that EGCG might promote the osteogenesis of hPDLCs in a dose-dependent manner, with concentrations of 4 and 6 µM EGCG showing the strongest osteogenic enhancement without cytotoxicity, indicating a promising role for EGCG in periodontal regeneration in patients with deficient alveolar bone in the future.

Association Between Periodontitis and Preeclampsia: A Bidirectional Mendelian Randomisation Analysis.

OBJECTIVES: Studies have increasingly focussed on the relationship between periodontitis (PD) and preeclampsia (PE). However, conclusions have not been consistent, and it is unclear whether any causal relationship exists between them and whether causality is bidirectional. This study employed Mendelian randomisation (MR) analysis to investigate the potential bidirectional causal relationship between PD and PE. METHODS: Genetic variants strongly linked to PD (17,353 cases and 28,210 controls), chronic periodontitis (CP; 1817 cases and 2215 controls), aggressive periodontitis (AgP; 851 cases and 6580 controls), and PE (7212 cases and 194,266 controls) in the genome-wide association study (GWAS) of European ancestry were used as instrumental variables (IVs). Inverse variance weighting (IVW) served as the primary method for causal inference. MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) was utilised to analyse horizontal pleiotropy. Cochrane Q tests and leave-one-out analyses were used to assess heterogeneity and stability amongst IVs. RESULTS: The MR analysis revealed no causal impacts of PD or its 2 subtypes-CP and AgP-on PE. Similarly, no significant causal effect of PE on PD was found in the reverse-MR analysis (IVW odds ratio, 0.97; 95% confidence interval, 0.91-1.05; P = .58). The findings from MR-Egger, weighted median, weighted mode, and the simple modelling approaches, as well as the pleiotropy and sensitivity analyses, aligned with those of the IVW method. CONCLUSIONS: The MR analysis suggests no bidirectional causal relationship between PD and PE; hence, PD and PE might not increase or prevent the risk of one other. CLINICAL RELEVANCE: Genetically, periodontitis or its subtypes chronic periodontitis and aggressive periodontitis may not require specific clinical attention to prevent the development of preeclampsia.

Bacteria-responsive programmed self-activating antibacterial hydrogel to remodel regeneration microenvironment for infected wound healing.

There is still an urgent need to develop hydrogels with intelligent antibacterial ability to achieve on-demand treatment of infected wounds and accelerate wound healing by improving the regeneration microenvironment. We proposed a strategy of hydrogel wound dressing with bacteria-responsive self-activating antibacterial property and multiple nanozyme activities to remodel the regeneration microenvironment in order to significantly promote infected wound healing. Specifically, pH-responsive H2O2 self-supplying composite nanozyme (MSCO) and pH/enzyme-sensitive bacteria-responsive triblock micelles encapsulated with lactate oxidase (PPEL) were prepared and encapsulated in hydrogels composed of L-arginine-modified chitosan (CA) and phenylboronic acid-modified oxidized dextran (ODP) to form a cascade bacteria-responsive self-activating antibacterial composite hydrogel platform. The hydrogels respond to multifactorial changes of the bacterial metabolic microenvironment to achieve on-demand antibacterial and biofilm eradication through transformation of bacterial metabolites, and chemodynamic therapy enhanced by nanozyme activity in conjunction with self-driven nitric oxide (NO) release. The composite hydrogel showed 'self-diagnostic' treatment for changes in the wound microenvironment. Through self-activating antibacterial therapy in the infection stage to self-adaptive oxidative stress relief and angiogenesis in the post-infection stage, it promotes wound closure, accelerates wound collagen deposition and angiogenesis, and completely improves the microenvironment of infected wound regeneration, which provides a new method for the design of intelligent wound dressings.

Membrane-anchoring selenophene viologens for antibacterial photodynamic therapy against periodontitis via restoring subgingival flora and alleviating inflammation.

Antibacterial photodynamic therapy (aPDT) has emerged as a promising strategy for treating periodontitis. However, the weak binding of most photosensitizers to bacteria and the hypoxic environment of periodontal pockets severely hamper the therapeutic efficacy. Herein, two novel oxygen-independent photosensitizers are developed by introducing selenophene into viologens and modifying with hexane chains (HASeV) or quaternary ammonium chains (QASeV), which improve the adsorption to bacteria through anchoring to the negatively charged cell membrane. Notably, QASeV binds only to the bacterial surface of Porphyromonas gingivalis and Fusobacterium nucleatum due to electrostatic binding, but HASeV can insert into their membrane by strong hydrophobic interactions. Therefore, HASeV exhibits superior antimicrobial activity and more pronounced plaque biofilm disruption than QASeV when combined with light irradiation (MVL-210 photoreactor, 350-600 nm, 50 mW/cm2), and a better effect on reducing the diversity and restoring the structure of subgingival flora in periodontitis rat model was found through 16S rRNA gene sequencing analysis. The histological and Micro-CT analyses reveal that HASeV-based aPDT has a better therapeutic effect in reducing periodontal tissue inflammation and alveolar bone resorption. This work provides a new strategy for the development of viologen-based photosensitizers, which may be a favorable candidate for the aPDT against periodontitis.

A telluroviologen-anchored tetraphenylporphyrin as sonosensitizer for periodontitis sonodynamic therapy.

Periodontitis is a chronic disease caused by bacteria (e.g. Porphyromonas gingivalis, P.gingivalis) that currently lacks effective non-invasive treatment options. Sonodynamic therapy (SDT) is an emerging non-invasive antimicrobial therapeutic strategy. Since ultrasonic tooth cleaning is widely used in dental treatments, SDT has significant potential for the facile implementation of treat periodontitis. However, hypoxia in periodontitis severely limits the effectiveness of traditional sonosensitizers. To address this issue, we have developed a new sonosensitizer termed as TPP-TeV, which combines the traditional sonosensitizer tetraphenylporphyrin (TPP) with a new photosensitizer telluroviologen (TeV). Under ultrasound radiation, TPP-TeV can produce numerous cationic free radicals (TPP-TeV•), which subsequently generate ROS free radicals (O2•-, •OH) efficiently via electron transfer mechanism, resulting in the effective killing of anaerobic P.gingivalis both in vivo and in vitro. As a result, the dental environment is improved, and the inhibition rate of alveolar bone loss reaches 80 %. The introduction of tellurium into the viologen molecule induces changes in its reduction potential, resulting in increased rigidity of the molecule. This modification systematically reduces the biotoxicity of our novel sonosensitizer by 75 % at 50 µM based on bacterial experiments. These promising findings could potentially establish new options for sonodynamic therapy (SDT) in periodontitis clinical treatments.

Nanoscaled Titanium Oxide Layer Provokes Quick Osseointegration on 3D-Printed Dental Implants: A Domino Effect Induced by Hydrophilic Surface.

Three-dimensional printing is a revolutionary strategy to fabricate dental implants. Especially, 3D-printed dental implants modified with nanoscaled titanium oxide layer (H-SLM) have impressively shown quick osseointegration, but the accurate mechanism remains elusive. Herein, we unmask a domino effect that the hydrophilic surface of the H-SLM facilitates blood wetting, enhances the blood shear rate, promotes blood clotting, and changes clot features for quick osseointegration. Combining computational fluid dynamic simulation and biological verification, we find a blood shear rate during blood wetting of the hydrophilic H-SLM 1.2-fold higher than that of the raw 3D-printed implant, which activates blood clot formation. Blood clots formed on the hydrophilic H-SLM demonstrate anti-inflammatory and pro-osteogenesis effects, leading to a 1.5-fold higher bone-to-implant contact and a 1.8-fold higher mechanical anchorage at the early stage of osseointegration. This mechanism deepens current knowledge between osseointegration speed and implant surface characteristics, which is instructive in surface nanoscaled modification of multiple 3D-printed intrabony implants.

Effect of pretreatment with calcium-containing desensitizer on the dentine bonding of mild self-etch adhesives.

Desensitizing agents are frequently applied to sensitive teeth and may affect subsequent resin bonding. The current study aimed to evaluate the bonding performance of two self-etch adhesives containing functional monomers to dentine pretreated with three new calcium-containing desensitizers. No desensitizer was applied in the control group. Groups 1, 2, and 3 were treated with an arginine-calcium carbonate-containing polishing paste, a casein phosphopeptide-amorphous calcium phosphate (CPP-ACP)-containing paste, and an experimental hydroxyapatite paste, respectively. G-Bond and Clearfil S(3) Bond were used for bonding after desensitizer treatments. The microtensile bond strength (µTBS) was tested (n = 20 beams per group) and failure mode distribution was analyzed. Scanning electron microscopy was used to observe the occlusion of dentinal tubules. The mean (±SD) µTBS values, expressed in MPa, of groups 1, 2, and 3 and the control group were, respectively, 30.81 (7.79), 44.41 (8.02), 31.49 (6.13), and 41.40 (8.67) for G-Bond and 39.63 (9.59), 32.55 (7.86), 37.50 (8.60), 27.90 (6.52) for S3 Bond. Most failures were recorded as adhesive failure (69.375%), instead of cohesive failure or mixed failure. The dentinal tubules were seldom plugged in group 2, but were mostly occluded in groups 1 and 3. Two-way anova indicated that desensitizer application in association with a compatible adhesive system should be used when endeavoring to control hypersensitivity without adverse interference in bonding.

Effect of a functional desensitizing paste containing 8% arginine and calcium carbonate on the microtensile bond strength of etch-and-rinse adhesives to human dentin.

PURPOSES: To evaluate (1) the effect of a desensitizing paste containing 8% arginine and calcium carbonate on the microtensile bond strength between dentin and etch-and-rinse adhesive systems; and (2) to examine the dentin tubules occlusion quantitatively. METHODS: 48 freshly extracted intact human mandibular third molars were divided randomly into three groups. The mid-coronal dentin of each tooth was exposed and treated. Group A: no treatment; Group B: specimens were polished with a desensitizing paste containing 8% arginine and calcium carbonate using a rotary cup operating at a low speed for 3 seconds, followed by an additional duration of 3 seconds (total operation time of 6 seconds), according to the manufacturer's instructions; Group C: specimens were handled in the same way with the exception of an increased operation time of 9 seconds, twice (total operation time of 18 seconds). Each group was randomly divided into two subgroups in order to evaluate the effectiveness of two different adhesive agents. A two-step etch-and-rinse adhesive agent (Adper SingleBond 2) and a three-step etch-and-rinse adhesive agent (Adper ScotchBond Multi-purpose) were applied to dentin surfaces. Then, microtensile bond strengths of the six subgroups were tested. Dentin surfaces were analyzed using field-emission scanning electron microscopy (FESEM) and laser scanning confocal microscopy (LSCM). RESULTS: There was no significant difference in microtensile bond strength between the control group and the experimental groups treated with the 8% arginine and calcium carbonate desensitizing paste during the application of etch-and-rinse adhesives. Both FESEM and LSCM showed that the desensitizing paste occluded dentin tubules effectively.