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Advanced Healthcare Materials · 2023 ·Vol. 12 ·期 19 ·2300100 · IF 10

In-Depth Occlusion of Dentinal Tubules and Rapid Remineralization of Demineralized Dentin Induced by Polyelectrolyte-Calcium Complexes

Zihuai Zhou,Jiachen Li,Zhe Wang,Hongli Zhang,Yiru Wang,Dongni Shen,Zhifang Wu,Minjuan Shen,Haihua Pan,Qi Wang,Ruikang Tang,Matthias Hannig,Baiping Fu

Dentin hypersensitivity (DH) is triggered by external stimuli irking fluid flow through exposed dentinal tubules (DTs). Three commercially available desensitizing agents as control in this study only achieve limited occlusion depths of ≈10 µm in the DTs as well as scarce remineralization of demineralized dentin matrix. Herein, polyelectrolyte-calcium complexes pre-precursor (PCCP) process is proposed for managing DH that demineralized dentin with exposed DTs is rubbed with ultrahighly concentrated polyelectrolyte-calcium suspension (4 g L −1 -5.44 m ) followed by phosphate solution (3.25 m ), each 10 min, leading to heavy remineralization of demineralized dentin and compact occlusion of the DTs over 200 µm after 1 day of in vitro and in vivo incubation. For the first time, it is demonstrated that the PCCP process relies on the pH-dependent electrostatic attraction between electropositive polyelectrolyte-calcium complexes and electronegative inwalls of DTs comprised of collagen fibrils and hydroxyapatite crystals under alkaline condition. The PCCP process might shed light on a promising dentin desensitizing strategy for DH management via rapid in-depth DT occlusion and remineralization of demineralized dentin.

研究领域: 牙科材料 · 牙科研究 · 生物矿化 · 材料科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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EUROPEAN JOURNAL OF ORAL SCIENCES · 2017 ·Vol. 125 ·期 5 ·396-402 · IF 1.54

Effect of maleic acid on the bond strength of fibre posts to root dentine

Fan Fan,Muhammad Ibrahim,Panpan Dai,Yixin Mao,Bing He,Gang Wu,Jianfeng Ma,Shengbin Huang

The aim of this study was to evaluate the effect of maleic acid (MA) on both the bond strength of fibre post to root dentine and smear layer removal after post space preparation. Sixty, single-canal premolars were endodontically treated and randomly assigned to four groups: group 1 [0.9% saline solution (control]); group 2 [2.5% sodium hypochlorite (NaOCl)]; group 3 [17% ethylenediaminetetraacetic acid (EDTA) followed by 2.5% NaOCl]; and group 4 (7% MA followed by 2.5% NaOCl). Self-adhesive resin cement was used to test the adhesion of a glass-fibre post to the root dentine through a micropush-out test. Scanning electron microscopy was performed to examine and score the treated specimens for smear layer removal, and stereomicroscopy was applied to investigate the failure modes of fibre posts. Maleic acid exhibited the highest mean bond-strength values in the apical regions among all the groups. Most failure modes (31.9%) were adhesive-type failures between the dentine and luting materials. Maleic acid performed statistically significantly better than the other groups regarding smear layer removal, especially in the apical region. Maleic acid is an effective irrigant that can remove the smear layer, open dentinal tubules, and act as a high-efficiency final irrigant in activation protocols.

研究领域: 牙科学 · 材料科学
✓ 已验证 DOI PubMed 高影响因子
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ADVANCED FUNCTIONAL MATERIALS · 2025 · IF 19

Biomimetic Janus Particles Induced In Situ Interfacial Remineralization for Dentin Hypersensitivity

Bing Han,Yilin Song,Shi Wang,Tiantian Yang,Zetao Sun,Aijing Wang,Moran Jin,Zhenzhong Yang,Xiaoyan Wang,Fuxin Liang

Dentin hypersensitivity (DH), caused by the exposure of dentin tubules, is a common complaint of dental patients. Although occlusion of the exposed tubules is the primary treatment approach, the complex oral environment, and multiple simultaneous requirements often hinder its implementation. In this study, strawberry-shaped hemispheric Janus particles (JPs) are synthesized, and their use in the treatment of DH is evaluated in vitro and in an animal model. The hemispheric side of the JPs is modified with polymers of quaternary ammonium salts (QASs) to form a superhydrophobic coating with antibiofilm properties, while the flat side is modified with catechol groups able to form strong bonds with dentin. Even after 1 h of ultrasonication or 1000 rounds of thermal cycling, the dentin tubules are completely occluded by the JPs. Moreover, biofilm formation is not observed, and the area of living bacteria is less than 1% compared to the blank control and sodium fluoride (NaF)-treated groups. In a rat model, the dentin tubules in the fixed specimens are completely occluded at day 3, much earlier than the occlusion obtained with commonly used NaF. These results demonstrate that JPs can provide a novel approach to the treatment of DH.

CAS / MDL: 127-65-1
研究领域: 口腔医学 · 材料科学
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ACS Omega · 2021 · IF 3.512

Study on Occluding Dentinal Tubules with a Nanosilver-Loaded Silica System In Vitro

Yang Zhou,Meng Yang,Qingjie Jia,Guojun Miao,Leilei Wan,Yi Zhang

The effects of most clinical treatments for dentin hypersensitivity are not long-lasting. To overcome the defects, the mesoporous silica nanoparticles and silver nanoparticles entered the field of oral materials. This study aimed to synthesize a novel, low-cytotoxic dentin desensitizer and investigate its occlusion effects on dentinal tubules. The biphasic stratification approach, a chemical reduction method, and the Stöber method were used to synthesize silver nanoparticle-loaded and nonporous silica-encapsulated mesoporous silica (Ag-MSNs@nSiO2), which was a noncrystalline structure with an average size of approximately 128 nm and a silver content of 3.506%. Atomic absorption spectrometry and the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide cell viability assay showed that Ag-MSNs@nSiO2 slowly released silver ions and had nearly no cytotoxicity. An electron microscope was used to observe the blocking effects on the dentinal tubules of sensitive tooth disc models, which were randomly divided into the following four groups: a deionized water group, a 5.9 M silver nitrate solution group, an Ag-MSNs@nSiO2 group, and a Gluma desensitizer group. There were no significant differences in the relative area of open dentinal tubules between the Ag-MSNs@nSiO2 group and the Gluma desensitizer group (P > 0.05). Detection of protein structures showed that multilevel structures of bovine serum albumin in dentin tubules were significantly changed by silver ions from Ag-MSNs@nSiO2. These results suggest that nearly noncytotoxic Ag-MSNs@nSiO2 was successfully synthesized by a series of methods. Ag-MSNs@nSiO2 occluded dentin tubules immediately and effectively. Moreover, the blockage effects may be enhanced and maintained by continuous condensation of proteins in dentinal tubules.

CAS / MDL: 13822-56-5
研究领域: 口腔医学 · 材料科学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Study on bionic mineralization of dentin using gallic acid as a linker for calcium phosphate nanocluster formation and collagen modification

Haide Dong,Danyang Wang,Yuzhu Liu,Lijuan Yin,Xiongying Wang,Yu Lu,Li Liu,Huan Zhang,Quanfu Deng,Weihu Yang,Kaiyong Cai

Dentin hypersensitivity and dental caries are prevalent symptoms and diseases in the oral cavity that markedly affect quality of life. The etiology of these conditions is directly or indirectly associated with the process of dentin demineralization and exposure. It is therefore imperative to identify an effective method for mineralizing demineralized dentin and sealing exposed dentin tubules. This study examines the potential of gallic acid, a polyphenol with a strong affinity for type I collagen, as a building block for calcium phosphate nanoclusters, with varying ratios of gallic acid to calcium. The objective is to utilize gallic acid as a linker to facilitate the docking, deposition, and mineralization of calcium phosphate nanoclusters and type I collagen. The study revealed that when the ratio of calcium to gallic acid was 0.05, calcium phosphate nanoclusters with an approximate particle size of 11.62 nm were formed. The nanoclusters were observed to effectively mineralize the intrafibrillar and interfibrillar spaces of type I collagen fibers, as well as the dentin itself. Following the mineralization treatment, the mechanical properties of the demineralized dentin were restored, and the depth of dentin tubule occlusion of 46.84 ± 12.83 μm, significantly reducing the permeability of dentin. This strategy demonstrates potential for clinical applications in the restoration of demineralized dentin and the treatment of dentin hypersensitivity.

研究领域: 口腔医学 · 生物矿化 · 材料科学
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DEVELOPMENT · 2023 ·Vol. 150 ·期 10 · IF 4.6

CHIP inhibits odontoblast differentiation through promoting DLX3 polyubiquitylation and degradation

Zheng Huiwen,Zhang Xiaobo,Fu Jing,Xue Yifan,Chen Zhi,Yang Guobin,Chen YiPing,Chen Di,Yuan Guohua

Dentin is the major hard tissue of teeth formed by differentiated odontoblasts. How odontoblast differentiation is regulated remains enigmatic. Here, we report that the E3 ubiquitin ligase CHIP is highly expressed in undifferentiated dental mesenchymal cells and downregulated after differentiation of odontoblasts. Ectopic expression of CHIP inhibits odontoblastic differentiation of mouse dental papilla cells, whereas knockdown of endogenous CHIP has opposite effects. Chip ( Stub1 ) knockout mice display increased formation of dentin and enhanced expression of odontoblast differentiation markers. Mechanistically, CHIP interacts with and induces K63 polyubiquitylation of the transcription factor DLX3, leading to its proteasomal degradation. Knockdown of DLX3 reverses the enhanced odontoblastic differentiation caused by knockdown of CHIP. These results suggest that CHIP inhibits odontoblast differentiation by targeting its tooth-specific substrate DLX3. Furthermore, our results indicate that CHIP competes with another E3 ubiquitin ligase, MDM2, that promotes odontoblast differentiation by monoubiquitylating DLX3. Our findings suggest that the two E3 ubiquitin ligases CHIP and MDM2 reciprocally regulate DLX3 activity by catalyzing distinct types of ubiquitylation, and reveal an important mechanism by which differentiation of odontoblasts is delicately regulated by divergent post-translational modifications.

研究领域: 分子生物学 · 发育生物学 · 牙科科学
✓ 已验证 DOI PubMed 高影响因子
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ACS Biomaterials Science & Engineering · 2022 · IF 5.395

Polyphenol-Enriched Extract of Lacquer Sap Used as a Dentine Primer with Benefits of Improving Collagen Cross-Linking and Antibacterial Functions

Ying Zhao,Xi He,Han Wang,Huimin Wang,Zuosen Shi,Song Zhu,Zhanchen Cui

Commercial dentin adhesive systems are applied to restorations due to their resistant bonding properties, but they suffer from the lack of bioactivity and are prone to hydrolysis. Therefore, to overcome these limitations, an eco-friendly natural monomer, urushiol, was adopted to be a primer in dentin bonding due to its interaction with collagen and antibacterial activity, preventing further hydrolysis development. First, urushiol was determined to be capable of improving the biological stability of dentin collagen through cross-linking. Using high-fidelity analytical chemistry techniques, such as Fourier transform infrared spectroscopy, we quantified the effects of urushiol on collagen molecules. It could also effectively decrease weight loss after collagenase ingestion by improving the stability of dentin. Moreover, urushiol inhibited Streptococcus mutans growth as well as its biofilm formation. Finally, we demonstrated that the urushiol primer could improve the bonding strength, particularly after aging. The cross-linking and antibacterial functions of urushiol have provided promising developmental prospects for biomaterials in dentin adhesion.

研究领域: 牙科材料 · 生物材料 · 牙科学 · 材料科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CELLULAR & MOLECULAR BIOLOGY LETTERS · 2024 · IF 9.2

KPNB1-ATF4 induces BNIP3-dependent mitophagy to drive odontoblastic differentiation in dental pulp stem cells

Zeying Zhang,Di Yang,Xiaoyuan Yan,Qiujing Qiu,Jiajie Guo,Lihong Qiu

Background Differentiating dental pulp stem cells (DPSCs) into odontoblasts is a critical process for tooth self-repair and dentine‒pulp engineering strategies in the clinic. However, the mechanism underlying the regulation of DPSC odontoblastic differentiation remains largely unknown. Here, we demonstrated that BCL-2 interacting protein 3 (BNIP3)-dependent mitophagy is associated with importin subunit beta-1 (KPNB1)-activating transcription factor 4 (ATF4), which promotes DPSC odontoblastic differentiation. Methods The key genes involved in DPSC odontogenic differentiation were identified via bioinformatics. Stable silencing or overexpression of BNIP3 was performed to investigate its impact on DPSC differentiation in vitro ( n  ≥ 3). To explore the role of BNIP3 in vivo, tooth root fragments loaded with the hydrogel-transfected DPSC complex were implanted into nude mice ( n  ≥ 6). Dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP) polymerase chain reaction (PCR) were conducted to explore the binding site of ATF4 to the BNIP3 promoter ( n  ≥ 3). Mitochondrial function experiments were performed to investigate the impact of ATF4-BNIP3 on mitochondria ( n  ≥ 3). Immunoprecipitation (IP) mass spectrometry (MS) was used to investigate the interaction between ATF4 and its binding protein, KPNB1. Plasmids containing wild-type (WT)/mutant (MUT)-nuclear localization signal (NLS) forms of ATF4 were constructed to determine the specific amino acid residues recognized by KPNB1 and their effects on DPSC odontoblastic differentiation ( n  ≥ 3). Results Compared with those in the control group, the levels of autophagy and mitophagy, especially BNIP3-dependent mitophagy, were greater in the DPSC odontoblastic differentiation group ( P  < 0.05). Genetic silencing or overexpression of BNIP3 demonstrated that BNIP3 expression was positively correlated with the transition of DPSCs into odontoblasts both in vitro and in vivo ( P  < 0.05). ATF4 regulates the expression of BNIP3 by directly binding to approximately −1292 to −1279 bp and approximately −1185 to −1172 bp within the BNIP3 promoter region, which is associated with mitophagy and mitochondrial reactive oxygen species (mtROS) levels ( P  < 0.05). Moreover, ATF4 increased mitophagy, mitochondrial function, and cell differentiation potential via BNIP3 ( P  < 0.05). Mechanistically, KPNB1 is a novel interacting protein of ATF4 that specifically recognizes amino acids (aa) 280–299 within ATF4 to control its translocation into the nucleus and subsequent transcription and differentiation processes ( P  < 0.05). Conclusions We reported that the critical role of KPNB1/ATF4/BNIP3 axis-dependent mitophagy could provide new cues for the regeneration of the dental pulp‒dentin complex in DPSCs. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1186/s11658-024-00664-9.

研究领域: 牙科学 · 干细胞生物学 · 分子生物学 · 细胞生物学
✓ 已验证 DOI PubMed 高影响因子
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Applied Materials Today · 2024 · IF 7.2

Sodium alginate-polyethylene glycol paste loaded with zinc-doped tricalcium phosphate particles for the treatment of dentin hypersensitivity

Hao Huang,Minjie Fan,Anchun Yang,Dongbiao Chang,Jinsheng Li,Liwen Yang,Xinlun Li,Mengyuan Wang,Pengfei Zheng,Tailin Guo,Jie Weng

β-tricalcium phosphate (β-TCP) has been widely applied in tissue engineering due to its excellent biocompatibility, degradability, and ability to induce mineralization. Zinc ion (Zn 2+ ) displays excellent antibacterial properties and a vital role in regulating cell metabolism. In this context, the incorporation of Zn 2+ into β-TCP to prepare Zn-doped β-tricalcium phosphate (Zn-β-TCP), emerges as a promising strategy for treating dentin hypersensitivity. However, delivering Zn-β-TCP effectively to the dentin surface for inducing mineralization of dentinal tubules remains a considerable challenge. In this study, we developed a sodium alginate-polyethylene glycol paste loaded with Zn-β-TCP particles, aiming to deliver Zn-β-TCP to the dentin surface for inducing mineralization. Zn-β-TCP particles were synthesized by the hydrothermal method and were combined with a sodium alginate-polyethylene glycol solution to create the Zn-β-TCP/sodium alginate/polyethylene glycol (Zn-β-TCP/SA/PEG) paste. In vitro experiments demonstrated that Zn-β-TCP could induce mineralization, exert good biocompatibility and antibacterial activity, promote dentin differentiation of dental pulp stem cells. Furthermore, Zn-β-TCP/SA/PEG exhibited excellent viscosity and effectively prompted the formation of a mineralized layer on dentin surfaces, successfully blocking dentinal tubules. Taken together, the present study demonstrated the potential of the Zn-β-TCP/SA/PEG paste as a promising therapeutic material for the treatment of dentin hypersensitivity.

CAS / MDL: 25322-68-3 9005-38-3
研究领域: 牙科材料 · 组织工程 · 生物材料科学 · 牙科学
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ORAL DISEASES · 2022 · IF 4.068

Erythropoietin induces odontoblastic differentiation of human-derived pulp stem cells via EphB4-Mediated MAPK signaling pathway

Deao Gu,Hanxiao Liu,Xinyi Qiu,Yijun Yu,Xuna Tang,Chao Liu,Leiying Miao

Objectives Human-derived pulp stem cells play key roles during dentinogenesis. Erythropoietin is reportedly involved in osteoblastogenesis and facilitates bone formation. However, the mechanism is still unknown. This research was to study the potential of erythropoietin in enhancing odontoblastic differentiation of human-derived pulp stem cells and to determine the underlying mechanism. Methods The human-derived pulp stem cells were treated with erythropoietin, EphB4 inhibitor, and MAPK inhibitors, and the odontoblastic differentiation was measured by ALP staining, ALP activity assay, alizarin red S staining, and their quantitative analysis, and RT-qPCR of DSPP, DMP1, OCN, and RUNX2. The direct pulp capping model was established to evaluate the formation of tertiary dentin after treatment with erythropoietin. Western blot assay was conducted to assess relevant protein expressions in the phosphorylated EphB4 and MAPK pathway. Results The results showed that erythropoietin promoted odontoblastic differentiation of human-derived pulp stem cells at 20 U/ml. Erythropoietin induced tertiary dentin formation in vivo. The potential mechanism of this was upregulating phosphorylated EphB4 and phosphorylated MAPK; furthermore, this effect could be decreased by EphB4 inhibitors, which inhibited MAPK phosphorylation. Blockage of MAPK pathways attenuated human-derived pulp stem cells’ odontoblastic differentiation, suggesting that MAPK pathways are involved. Conclusion Erythropoietin induced tertiary dentin formation in vivo. And erythropoietin enhanced human-derived pulp stem cells' odontoblastic differentiation via the EphB4-mediated MAPK signaling pathway.

研究领域: 牙科学 · 干细胞研究 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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Materials Today Bio · 2022 · IF 10.761

Carbon dots enhance extracellular matrix secretion for dentin-pulp complex regeneration through PI3K/Akt/mTOR pathway-mediated activation of autophagy

Lili Liu,Xianjing Li,Wenhuan Bu,Nianqiang Jin,Yuan Meng,Yi Wang,Duan Wang,Xiaowei Xu,Ding Zhou,Hongchen Sun

Pulp injury is one of the most common clinical diseases, and severe cases are usually associated with the functional loss of the tooth, while the current clinical treatment modality is only a cavity filling procedure without the regeneration of the dentin-pulp complex, thus leading to a devitalized and brittle tooth. In this study, carbon dots (CDots) with excellent biocompatibility are prepared from ascorbic acid and polyethyleneimine via a hydrothermal method. The as-prepared CDots can enhance extracellular matrix (ECM) secretion of human dental pulp stem cells (DPSCs), giving rise to increased cell adhesion on ECM and a stronger osteogenic/odontogenic differentiation capacity of DPSCs. Further, the mechanism underlying CDots-enhanced ECM secretion is revealed by the transcriptome analysis, Western blot assay and molecular dynamics simulation, identifying that the pharmacological activities of CDots are originated from a reasonable activation of the autophagy, which is mediated by regulating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway. Based on the abundant CDots-induced ECM and thereby the reinforcement of the cell-ECM adhesion, an intact dental pulp stem cell sheet can be achieved, which in return promote in vivo the efficient regeneration of dentin-pulp complex as well as blood vessels.

CAS / MDL: 9002-98-6
研究领域: 材料科学 · 生物材料 · 组织工程 · 干细胞生物学 · 牙科研究
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JOURNAL OF MATERIALS SCIENCE · 2023 ·Vol. 58 ·期 31 ·12685-12705 · IF 4.5

Evaluation of the effects of combined application of dimethylaminohexadecyl methacrylate and MDP on dentin bonding and antimicrobial properties

Shen Jiadi,Ma Ming,Huang Yun,Miao Haochen,Wei Xin

This study aimed to evaluate the effects of the combined application of dimethylaminohexadecyl methacrylate (DMAHDM) and 10-methacryloyloxydecyl dihydrogen phosphate (MDP) on dentin bonding and its antimicrobial properties. DMAHDM was incorporated into the adhesives at 5% by mass, where two commercial adhesives were used: (1) MDP-free adhesive (single bond 2); (2) MDP-containing adhesive (single bond universal, SBU). The microtensile bond strength (μTBS) and nanoleakage were analyzed on the combination. The effects of DMAHDM on the interaction between MDP and hydroxyapatite and the degree of conversion were assessed by Fourier transform infrared spectroscopy (FTIR). Antimicrobial properties were examined by live/dead staining assay, colony-forming units (CFU), and metabolic activity, and cytotoxicity was measured using cell counting kit-8 (CCK-8) assay. 5% DMAHDM or MDP-containing groups showed increased immediate μTBS compared with the control group. Nanoleakage showed that 5% DMAHDM or MDP-containing groups presented little amount of silver penetration, while the control group exhibited extensive silver uptake along the bonding interface after water storage aging. FTIR showed that the interaction between MDP and hydroxyapatite was not affected by DMAHDM, besides DMAHDM did not hamper the polymerization of the bonding agents. The adhesives added with DMAHDM inhibited biofilm formation and reduced the biofilm CFU and metabolic activity of Candida albicans and Streptococcus mutans ( P  < 0.05). No cytotoxic or slight cytotoxic effect was detected for the experimental materials used (MDP and 5% DMAHDM). The addition of DMAHDM along with MDP can obtain improved dentin bonding with increased antimicrobial performance.

研究领域: 牙科材料学 · 生物医学工程
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