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Bone defects caused by tumors, osteoarthritis, and osteoporosis attract great attention. Because of outstanding biocompatibility, osteogenesis promotion, and less secondary infection incidence ratio, stimuli-responsive biomaterials are increasingly used to manage this issue. These biomaterials respond to certain stimuli, changing their mechanical properties, shape, or drug release rate accordingly. Thereafter, the activated materials exert instructive or triggering effects on cells and tissues, match the properties of the original bone tissues, establish tight connection with ambient hard tissue, and provide suitable mechanical strength. In this review, basic definitions of different categories of stimuli-responsive biomaterials are presented. Moreover, possible mechanisms, advanced studies, and pros and cons of each classification are discussed and analyzed. This review aims to provide an outlook on the future developments in stimuli-responsive biomaterials.

Background: A major disadvantage of polymethyl methacrylate (PMMA) acrylic resins is susceptibility to biofilm accumulation. The incorporation of antimicrobial agents is a reliable prevention technique. The purpose of this study is to investigate the effect of incorporating dimethylaminohexadecyl methacrylate (DMAHDM) and/or 2-methacryloyloxyethyl phosphorylcholine (MPC) into heat-polymerized (HP) and 3D-printed (3DP) denture base materials on the flexural strength, modulus of elasticity, and surface hardness. Methods: DMAHDM and/or MPC were mixed with the acrylic resin liquid of a heat-polymerized (ProBase Hot) and a 3D printed (NextDent Denture 3D) material at mass fractions of 1.5% and 3% and a combination of 3% MPC and 1.5% DMAHDM. Results: Significant differences in mechanical properties between the control and experimental groups have been detected (p-value < 0.0001). In HP materials, the addition of DMAHDM and/or MPC generally decreased the flexural strength, from (151.18 MPa) in G1 down to (62.67 MPa) in G5, and surface hardness, from (18.05 N/mm2) down to (10.07 N/mm2) in G5. Conversely, in 3DP materials, flexural strength was slightly enhanced, from (58.22 MPa) in G1 up to (62.76 MPa) in G6, although surface hardness was consistently reduced, from (13.57 N/mm2) down to (5.29 N/mm2) in G5. Conclusion: It is recommended to carefully optimize the concentrations of DMAHDM and/or MPC to maintain mechanical integrity.

The study aimed to develop a biodegradable scaffold incorporating valproic acid (VPA) for improved human bone marrow-derived mesenchymal stem cell (hBMSC) proliferation, differentiation, and bone mineral synthesis. A chitosan–gelatin (CH-G) scaffold was fabricated and loaded with varying concentrations of VPA (1, 3, 5 mM/L). In vitro studies assessed drug release, cell proliferation, morphology, mineralization, and gene expression. VPA was rapidly released from the scaffold, with over 90% cumulative release within seven days. Cells cultured on VPA-loaded scaffolds exhibited significantly enhanced proliferation and mineralization compared to the control. VPA treatment upregulated osteocalcin and runt-related transcription factor 2 (Runx-2) expression, key markers of osteogenic differentiation. The CH-G scaffold, particularly with 1 mM/L VPA, demonstrates excellent biocompatibility and promotes hBMSC-mediated bone regeneration. This novel approach holds promise for future applications in bone tissue engineering.

Streptococcus mutans (S. mutans) antisense vicK RNA (ASvicK) is a non-coding RNA that regulates cariogenic virulence and metabolic activity. Dimethylaminohexadecyl methacrylate (DMAHDM), a quaternary ammonium methacrylate used in dental materials, has strong antibacterial activity. This study examined the effects of S. mutans ASvicK on DMAHDM susceptibility and their combined impact on inhibiting S. mutans biofilm formation and protecting enamel hardness. The parent S. mutans UA159 and ASvicK overexpressing S. mutans (ASvicK) were tested. The minimum inhibitory concentration (MIC) and minimum bactericidal concentrations for planktonic bacteria (MBC-P) and biofilms (MBC-B) were measured. As the ASvicK MBC-B was 175 μg/mL, live/dead staining, metabolic activity (MTT), colony-forming units (CFUs), biofilm biomass, polysaccharide, and lactic acid production were investigated at 175 μg/mL and 87.5 μg/mL. The MIC, MBC-P, and MBC-B values for DMAHDM for the ASvicK strain were half those of the UA159 strain. In addition, combining S. mutans ASvicK with DMAHDM resulted in a significant 4-log CFU reduction (p < 0.05), with notable decreases in polysaccharide levels and lactic acid production. In the in vitro cariogenic model, the combination achieved the highest enamel hardness at 67.1% of sound enamel, while UA159 without DMAHDM had the lowest at 16.4% (p < 0.05). Thus, S. mutans ASvicK enhanced DMAHDM susceptibility, and their combination effectively inhibited biofilm formation and minimized enamel demineralization. The S. mutans ASvicK + DMAHDM combination shows great potential for anti-caries dental applications.

This study aimed to synthesize a novel elastomeric ligature with dimethylaminohexadecyl methacrylate (DMAHDM) grafted, providing a new strategy for improving the issue of enamel demineralization during fixed orthodontics. DMAHDM was incorporated into elastomeric ligatures at different mass fractions using ultraviolet photochemical grafting. The antibacterial properties were evaluated and the optimal DMAHDM amount was determined based on cytotoxicity assays. Moreover, tests were conducted to evaluate the in vivo changes in the mechanical properties of the elastomeric ligatures. To assess the actual in vivo effectiveness in preventing enamel demineralization, a rat demineralization model was established, with analyses focusing on changes in surface microstructure, elemental composition, and nanomechanical properties. Elastomeric ligatures with 2% DMAHDM showed excellent biocompatibility and the best antibacterial properties, reducing lactic acid production by 65.3% and biofilm bacteria by 50.0% within 24 h, without significant mechanical property differences from the control group (p > 0.05). Most importantly, they effectively prevented enamel demineralization in vivo, enhancing elastic modulus by 73.2% and hardness by 204.8%. Elastomeric ligatures incorporating DMAHDM have shown great potential for application in preventing enamel demineralization, providing a new strategy to solve this issue during fixed orthodontics.

Root caries caused by cariogenic bacteria are a burden on a large number of individuals worldwide, especially the elderly. Applying a protective coating to exposed root surfaces has the potential to inhibit the development of caries, thus preserving natural teeth. This study aimed to develop a novel antibacterial coating to combat root caries and evaluate its effectiveness using the antibacterial monomer dimethylaminohexadecyl methacrylate (DMAHDM). DMAHDM was synthesized and incorporated into a resin consisting of 55.8% urethane dimethacrylate (UDMA) and 44.2% TEG-DVBE (UV) at a 10% mass fraction of glass filler. Multiple concentrations of DMAHDM were tested for their impact on the resin’s mechanical and physical properties. S. mutans biofilms grown on resin disks were analyzed for antibacterial efficacy. Cytotoxicity was assessed against human gingival fibroblasts (HGFs). The results showed an 8-log reduction in colony-forming units (CFUs) against S. mutans biofilm (mean ± sd; n = 6) (p < 0.05) when 5% DMAHDM was incorporated into the UV resin. There was a 90% reduction in metabolic activity and lactic acid production. A low level of cytotoxicity against HGF was observed without compromising the physical and mechanical properties of the resin. This coating material demonstrated promising physical properties, potent antibacterial effects, and low toxicity, suggesting its potential to protect exposed roots from caries in various dental procedures and among elderly individuals with gingival recession.

Abstract Antimicrobial photodynamic therapy (aPDT) shows promise in eliminating oral pathogens without inducing microbial resistance. Yet, it faces limited biofilm penetration by the photosensitizer, which hinders its efficacy against mature, thick biofilms. This study assesses the effectiveness of the MagTBO (magnetic nanoparticles and toluidine‐blue ortho) nanoplatform against mature Streptococcus mutans biofilms associated with dental caries. The study employs constant‐depth film fermenter (CDFF) models, known as “artificial mouth,” to replicate caries processes and allow biofilm growth over teeth. This method enables the evaluation of biofilm‐induced mineral loss under cariogenic challenge over 5 and 10 days. The study shows that MagTBO improves aPDT's effectiveness against highly mature and complex biofilms over 5 and 10 days. However, the biofilm reduction unaffected the mineral content in the underlying dentin. This presents a promising approach for clinical aPDT protocols. However, it is crucial to acknowledge that these findings are based on in vitro studies and may necessitate further clinical confirmation. In summary, our data indicate that magnetic‐based photosensitizers enhance the modulation of pathogenic oral biofilms by aPDT, offering potential advancements in clinical aPDT protocols.

Abstract Background The present study aimed to develop a novel protein-repellent and antibacterial polymethyl methacrylate (PMMA) dental resin with 2-methacryloyloxyethyl phosphorylcholine (MPC) and quaternary ammonium dimethylaminohexadecyl methacrylate (DMAHDM), and to investigate the effects of water-aging for 6 months on the mechanical properties, protein adsorption, and antibacterial activity of the dental resin. Methods Four groups were tested: PMMA control; PMMA + 3% MPC; PMMA + 1.5% DMAHDM; and PMMA + 3% MPC + 1.5% DMADDM in acrylic resin powder. Specimens were water-aged for 1 d, 3 months, and 6 months at 37 ℃. Their mechanical properties were then measured using a three-point flexure test. Protein adsorption was measured using a micro bicinchoninic acid (BCA) method. A human saliva microcosm model was used to inoculate bacteria on water-aged specimens and to investigate the live/dead staining, metabolic activity of biofilms, and colony-forming units (CFUs). Results The flexural strength and elastic modulus showed a significant loss after 6 months of water-ageing for the PMMA control (mean ± SD; n = 10); in contrast, the new protein repellent and antibacterial PMMA resin showed no strength loss. The PMMA–MPC–DMAHDM-containing resin imparted a strong antibacterial effect by greatly reducing biofilm viability and metabolic activity. The biofilm CFU count was reduced by about two orders of magnitude (p 0.05). Conclusions The flexural strength and elastic modulus of the PMMA–MPC–DMAHDM-containing resin were superior to those of the PMMA control after 6 months of water-ageing. The novel PMMA resin incorporating MPC and DMAHDM exhibited potent and lasting protein-repellent and antibacterial properties.

Recurrent caries remain a persistent concern, often linked to microleakage and a lack of bioactivity in contemporary dental composites. Our study aims to address this issue by developing a low-shrinkage-stress nanocomposite with antibiofilm and remineralization capabilities, thus countering the progression of recurrent caries. In the present study, we formulated low-shrinkage-stress nanocomposites by combining triethylene glycol divinylbenzyl ether and urethane dimethacrylate, incorporating dimethylaminododecyl methacrylate (DMADDM), along with nanoparticles of calcium fluoride (nCaF2) and nanoparticles of amorphous calcium phosphate (NACP). The biofilm viability, biofilm metabolic activity, lactic acid production, and ion release were evaluated. The novel formulations containing 3% DMADDM exhibited a potent antibiofilm activity, exhibiting a 4-log reduction in the human salivary biofilm CFUs compared to controls (p < 0.001). Additionally, significant reductions were observed in biofilm biomass and lactic acid (p < 0.05). By integrating both 10% NACP and 10% nCaF2 into one formulation, efficient ion release was achieved, yielding concentrations of 3.02 ± 0.21 mmol/L for Ca, 0.5 ± 0.05 mmol/L for P, and 0.37 ± 0.01 mmol/L for F ions. The innovative mixture of DMADDM, NACP, and nCaF2 displayed strong antibiofilm effects on salivary biofilm while concomitantly releasing a significant amount of remineralizing ions. This nanocomposite is a promising dental material with antibiofilm and remineralization capacities, with the potential to reduce polymerization-related microleakage and recurrent caries.

Oral cavity is an essential reservoir for H. pylori. We aimed to investigate the antibacterial effects of dimethylaminododecyl methacrylate (DMADDM) against H. pylori. Modified giomers were prepared by introducing 0%, 1.25% and 2.5% DMADDM monomers. Broth microdilution assay, spot assay, Alamer Blue assay, PMA–qPCR, crystal violet staining, scanning electron microscopy observation and live/dead bacterial staining were performed to evaluate the antibacterial and antibiofilm effects of DMADDM and modified giomers in vitro. Urease assay, qPCR, hematoxylin–eosin staining and ELISA were performed to evaluate the inflammation levels and colonization of H. pylori in vivo. In vitro experiments indicated that the minimum inhibitory concentration and minimum bactericidal concentration of DMADDM were 6.25 μg/mL and 25 μg/mL, respectively. It inhibited H. pylori in a dose- and time-dependent manner, and significantly reduced the expression of cagA, vacA, flaA and ureB. DMADDM-modified giomers inhibited the formation of H. pylori biofilm and reduced live cells within it. In vivo experiments confirmed that the pretreatment with DMADDM-modified dental resin effectively reduced the gastric colonization of oral–derived H. pylori, suppressed systemic and local gastric inflammation. DMADDM monomers and DMADDM-modified giomers possessed excellent antibacterial and antibiofilm effects on H. pylori. Pretreatment with DMADDM-modified giomers significantly inhibited the gastric infection by H. pylori.

Objectives: Stem cell-based tissue engineering approaches are promising for bone repair and regeneration. Periodontal ligament stem cells (PDLSCs) are a promising cell source for tissue engineering, especially for maxillofacial bone and periodontal regeneration. Many studies have shown potent results via PDLSCs in bone regeneration. In this review, we describe recent cutting-edge researches on PDLSC-based bone regeneration and periodontal tissue regeneration.Data and sources: An extensive search of the literature for papers related to PDLSCs-based bioactive constructs for bone tissue engineering was made on the databases of PubMed, Medline and Google Scholar. The papers were selected by three independent calibrated reviewers.Results: Multiple types of materials and scaffolds have been combined with PDLSCs, involving xeno genic bone graft, calcium phosphate materials and polymers. These PDLSC-based constructs exhibit the potential for bone and periodontal tissue regeneration. In addition, various osteo inductive agents and strategies have been applied with PDLSCs, including drugs, biologics, gene therapy, physical stimulation, scaffold modification, cell sheets and co-culture.Conclusoin: This review article demonstrates the great potential of PDLSCs-based bioactive constructs as a promising approach for bone and periodontal tissue regeneration.

Abstract Background Enterococcus faecalis (E. faecalis) is the most recovered species from the root canals after failed root canal treatment. Calcium phosphate bone cement (CPC) scaffold is promising for applications in endodontic treatment as a kind of root canal sealer. Graphene oxide (GO) has been extensively considered as a kind of promising nano-materials for antibacterial applications. In the present study, an injectable CPC-chitosan paste containing GO was developed for promising endodontic therapy. The antibacterial properties of this paste against E. faecalis biofilms as well as the support for human dental pulp stem cells (hDPSCs) were investigated. Methods CPC-chitosan composite with or without GO injectable scaffold was fabricated. The hDPSC growth and viability on scaffolds were investigated by live/dead assay. Antibacterial effects against E. faecalis biofilms were determined in clinical detin block samples. Results The antibacterial CPC-chitosan-GO disks had excellent hDPSC support with the percentages of live cells at around 90%. CPC-chitosan-GO also had greater antibacterial activity on E. faecalis than that of CPC-chitosan control using detin block models (p

ObjectivesWhite spot lesions (WSLs) are prevalent and often lead to aesthetic problems and progressive caries. The objectives of this study were to: (1) develop a novel resin infiltrant containing smart monomer dodecylmethylaminoethyl methacrylate (DMAEM) to inhibit WSLs, and (2) investigate the effects of DMAEM incorporation on cytotoxicity, mechanical properties, biofilm-inhibition and protection of enamel hardness for the first time.MethodsDMAEM was synthesized using 1-bromododecane, 2-methylamino ethanol and methylmethacrylate. DMAEM with mass fractions of 0%, 1.25%, 2.5% and 5% were incorporated into a resin infiltant containing BisGMA and TEGDMA. Cytotoxicity, mechanical properties and antibacterial effects were tested. After resin infiltration, bovine enamel was demineralized with saliva biofilm acids, and enamel hardness was measured.ResultDMAEM infiltration did not increase the cytotoxicity or compromise the physical properties when DMAEM mass fraction was below 5% (p > 0.05). Biofilm metabolic activity was reduced by 90%, and biofilm lactic acid production was reduced by 92%, via DMAEM (p < 0.05). Mutans streptococci biofilm CFU was reduced by 3 logs (p < 0.05). When demineralized in acid and then under biofilms, the infiltrant + 5% DMAEM group produced an enamel hardness (mean ± sd; n = 6) of 2.90 ± 0.06 GPa, much higher than 0.85 ± 0.12 GPa of the infiltrant + 0% DMAEM group (p < 0.05).SignificanceA novel resin infiltrant with excellent mechanical properties, biocompability, strong antibacterial activity and anti-demineralization effect was developed using DMAEM for the first time. The DMAEM resin infiltrant is promising for inhibiting WSLs, arresting early caries, and protecting enamel hardness.

Objectives: 1) Develop a novel construct of human periodontal ligament stem cells (hPDLSCs) encapsulated in degradable alginate microbeads (DAMB) with human platelet lysate (hPL) and injectable calcium phosphate cement (ICPC); 2) Investigate the proliferation and osteogenic differentiation of hPDLSCs in ICPC with hPL as a xeno-free supplement and animal serum replacement for bone tissue engineering applications.Methods: hPDLSCs were encapsulated in alginate-fibrin microbeads (DAMB + fibrin), alginate-hPL degradable microbeads (DAMB + hPL), or alginate-fibrin-hPL microbeads (DAMB + fibrin + hPL). The proliferation and osteogenic differentiation of hPDLSCs were investigated in culturing with the ICPC scaffold.Results: Flexural strength of ICPC was 8.4 ± 0.91 MPa, and elastic modulus was 1.56 ± 0.1 GPa, exceeding those of cancellous bone. hPDLSCs had higher viability in DAMB + fibrin + hPL group than in DAMB + fibrin. ALP was 69.97 ± 16.96 mU/mg for ICPC + DAMB + fibrin + hPL group, higher than 30.68 ± 2.86 mU/mg of ICPC + DAMB + fibrin (p < 0.05) and 4.12 ± 1.65 mU/mg of control (p < 0.01). At 7 days, osteogenic gene expressions (ALP, RUNX2, COL1, and OPN) in ICPC + DAMB + fibrin + hPL and ICPC + DAMB + fibrin were 4–11 folds that of control. At 21 days, the hPDLSC-synthesized bone mineral amounts in ICPC + DAMB + fibrin + hPL and ICPC + DAMB + fibrin were 13.2 folds and 11.1 folds that of control group, respectively.Conclusion: The novel injectable CPC scaffold encapsulating hPDLSCs and hPL is promising to protect and deliver hPDLSCs. The hPL-based medium significantly enhanced the osteogenic differentiation of hPDLSCs in ICPC + DAMB + fibrin + hPL construct, suggesting a promising xeno-free approach for bone tissue regeneration applications.

Extracellular vesicles (EVs) are a class of nanoparticles that are derived from almost any type of cell in the organism tested thus far and are present in all body fluids. With the capacity to transfer “functional cargo and biological information” to regulate local and distant intercellular communication, EVs have developed into an attractive focus of research for various physiological and pathological conditions. The oral cavity is a special organ of the human body. It includes multiple types of tissue, and it is also the beginning of the digestive tract. Moreover, the oral cavity harbors thousands of bacteria. The importance and particularity of oral function indicate that EVs derived from oral cavity are quite complex but promising for further research. This review will discuss the extensive source of EVs in the oral cavity, including both cell sources and cell-independent sources. Besides, accumulating evidence supports extensive biomedical applications of extracellular vesicles in oral tissue regeneration and development, diagnosis and treatment of head and neck tumors, diagnosis and therapy of systemic disease, drug delivery, and horizontal gene transfer (HGT). The immune cell source, odontoblasts and ameloblasts sources, diet source and the application of EVs in tooth development and HGT were reviewed for the first time. In conclusion, we concentrate on the extensive source and potential applications offered by these nanovesicles in oral science.

Objectives: Composites are commonly used for tooth restorations, but recurrent caries often lead to restoration failures due to polymerization shrinkage-stress-induced marginal leakage. The aims of this research were to: (1) develop novel low-shrinkage-stress (L.S.S.) nanocomposites containing dimethylaminododecyl methacrylate (DMADDM) with nanoparticles of calcium fluoride (nCaF2) or amorphous calcium phosphate (NACP) for remineralization; (2) investigate antibacterial and cytocompatibility properties. Methods: Nanocomposites were made by mixing triethylene glycol divinylbenzyl ether with urethane dimethacrylate containing 3% DMADDM, 20% nCaF2, and 20% NACP. Flexural strength, elastic modulus, antibacterial properties against Streptococcus mutans biofilms, and cytotoxicity against human gingival fibroblasts and dental pulp stem cells were tested. Results: Nanocomposites with DMADDM and nCaF2 or NACP had flexural strengths matching commercial composite control without bioactivity. The new nanocomposite provided potent antibacterial properties, reducing biofilm CFU by 6 logs, and reducing lactic acid synthesis and metabolic function of biofilms by 90%, compared to controls (p < 0.05). The new nanocomposites produced excellent cell viability matching commercial control (p > 0.05). Conclusions: Bioactive L.S.S. antibacterial nanocomposites with nCaF2 and NACP had excellent bioactivity without compromising mechanical and cytocompatible properties. The new nanocomposites are promising for a wide range of dental restorations by improving marginal integrity by reducing shrinkage stress, defending tooth structures, and minimizing cariogenic biofilms.

Objectives: Current dental resins exhibit polymerization shrinkage causing microleakage, which has the potential to cause recurrent caries. Our objectives were to create and characterize low-shrinkage-stress (LSS) composites with dimethylaminododecyl methacrylate (DMADDM) as an antibacterial agent to combat recurrent caries. Methods: Triethylene glycol divinylbenzyl ether and urethane dimethacrylate were used to reduce shrinkage stress. DMADDM was incorporated at different mass fractions (0%, 1.5%, 3%, and 5%). Flexural strength, elastic modulus, degree of conversion, polymerization stress, and antimicrobial activity were assessed. Results: The composite with 5% DMADDM demonstrated higher flexural strength than the commercial group (p < 0.05). The addition of DMADDM in BisGMA-TEGDMA resin and LSS resin achieved clinically acceptable degrees of conversion. However, LSS composites exhibited much lower polymerization shrinkage stress than BisGMA-TEGDMA composite groups (p < 0.05). The addition of 3% and 5% DMADDM showed a 6-log reduction in Streptococcus mutans (S. mutans) biofilm CFUs compared to commercial control (p < 0.001). Biofilm biomass and lactic acid were also substantially decreased via DMADDM (p < 0.05). Conclusions: The novel LSS dental composite containing 3% DMADDM demonstrated potent antibacterial action against S. mutans biofilms and much lower polymerization shrinkage-stress, while maintaining excellent mechanical characteristics. The new composite is promising for dental applications to prevent secondary caries and increase restoration longevity.

Bone tissue engineering is a promising approach that uses seed-cell-scaffold drug delivery systems to reconstruct bone defects caused by trauma, tumors, or other diseases (e.g., periodontitis). Metformin, a widely used medication for type II diabetes, has the ability to enhance osteogenesis and angiogenesis by promoting cell migration and differentiation. Metformin promotes osteogenic differentiation, mineralization, and bone defect regeneration via activation of the AMP-activated kinase (AMPK) signaling pathway. Bone tissue engineering depends highly on vascular networks for adequate oxygen and nutrition supply. Metformin also enhances vascular differentiation via the AMPK/mechanistic target of the rapamycin kinase (mTOR)/NLR family pyrin domain containing the 3 (NLRP3) inflammasome signaling axis. This is the first review article on the effects of metformin on stem cells and bone tissue engineering. In this paper, we review the cutting-edge research on the effects of metformin on bone tissue engineering. This includes metformin delivery via tissue engineering scaffolds, metformin-induced enhancement of various types of stem cells, and metformin-induced promotion of osteogenesis, angiogenesis, and its regulatory pathways. In addition, the dental, craniofacial, and orthopedic applications of metformin in bone repair and regeneration are also discussed.

Persistent apical periodontitis is a critical challenge for endodontists. Developing root canal filling materials with continuous antibacterial effects and tightly sealed root canals are essential strategies to avoid the failure of root canal therapy and prevent persistent apical periodontitis. We modified the EndoREZ root canal sealer with the antibacterial material dimethylaminododecyl methacrylate (DMADDM) and magnetic nanoparticles (MNPs). The mechanical properties of the modified root canal sealer were tested. The biocompatibility of this sealer was verified in vitro and in vivo. Multispecies biofilms were constructed to assess the antibacterial effects of the modified root canal sealer. We applied magnetic fields and examined the extent of root canal sealer penetration in vitro and in vivo. The results showed that EndoREZ sealer containing 2.5% DMADDM and 1% MNP had biological safety and apical sealing ability. In addition, the modified sealer could increase the sealer penetration range and exert significant antibacterial effects on multispecies biofilms under an external magnetic field. According to the in vivo study, the apices of the root canals with the sealer containing 2.5% DMADDM and 1% MNP showed no significant resorption and exhibited only a slight increase in the periodontal ligament space, with a good inhibitory effect on persistent apical periodontitis.

This study aimed to modify EndoREZ with 2.5% dimethylaminododecyl methacrylate (DMADDM) and 1% magnetic nanoparticles (MNP) to study its sealing property, penetration and long-term antibacterial and therapeutic effect in the single-cone technique (SCT) compared with EndoREZ and iRoot SP. Thirty single-root human maxillary premolars were assigned into three groups and obturated with three different root canal sealers by SCT. Every specimen was then scanned using micro-CT to analyze void fraction, and void volumes and confocal laser scanning microscope (CLSM) was used to study the dentin penetration. The long-term antimicrobial effects were tested in vitro before and after aging 1 and 4 weeks by the single-strain Enterococcus faecalis biofilm model. In addition, the beagle canine model of apical periodontitis (AP) was utilized to judge and compare the therapeutic effect of three sealers in SCT. The void fraction and void volumes of the modified root canal sealer were not significantly different from iRoot SP (p > 0.05) but were lower than EndoREZ (p < 0.05). The modified root canal sealant displayed a greater penetration, long-term antibacterial property, and treatment effect than the other groups (p < 0.05). This indicated that after being modified with DMADDM and MNP, it showed better performance in SCT.

The objectives of this study were to investigate the effects of a novel method using flavonoids to inhibit Streptococcus mutans (S. mutans), Candida albicans (C. albicans) and dual-species biofilms and to protect enamel hardness in a biofilm-based caries model for the first time. Several flavonoids, including baicalein, naringenin and catechin, were tested. Gold-standard chlorhexidine (CHX) and untreated (UC) groups served as controls. Optimal concentrations were determined by cytotoxicity assay. Biofilm MTT, colony-forming-units (CFUs), biofilm biomass, lactic acid and polysaccharide production were evaluated. Real-time-polymerase-chain reaction (qRT-PCR) was used to determine gene expressions in biofilms. Demineralization of human enamel was induced via S. mutans-C. albicans biofilms, and enamel hardness was measured. Compared to CHX and UC groups, the baicalein group achieved the greatest reduction in S. mutans, C. albicans and S. mutans-C. albicans biofilms, yielding the least metabolic activity, polysaccharide synthesis and lactic acid production (p < 0.05). The biofilm CFU was decreased in baicalein group by 5 logs, 4 logs, 5 logs, for S. mutans, C. albicans and S. mutans-C. albicans biofilms, respectively, compared to UC group. When tested in a S. mutans-C. albicans in vitro caries model, the baicalein group substantially reduced enamel demineralization under biofilms, yielding an enamel hardness that was 2.75 times greater than that of UC group. Hence, the novel baicalein method is promising to inhibit dental caries by reducing biofilm formation and protecting enamel hardness.

The management and treatment of dental and craniofacial injuries have continued to evolve throughout the last several decades. Limitations with autograft, allograft, and synthetics created the need for more advanced approaches in tissue engineering. Calcium phosphate cements (CPC) are frequently used to repair bone defects. Since their discovery in the 1980s, extensive research has been conducted to improve their properties, and emerging evidence supports their increased application in bone tissue engineering. This review focuses on the up-to-date performance of calcium phosphate cement (CPC) scaffolds and upcoming promising dental and craniofacial bone regeneration strategies. First, we summarized the barriers encountered in CPC scaffold development. Second, we compiled the most up to date in vitro and in vivo literature. Then, we conducted a systematic search of scientific articles in MEDLINE and EMBASE to screen the related studies. Lastly, we revealed the current developments to effectively design CPC scaffolds and track the enhanced viability and therapeutic efficacy to overcome the current limitations and upcoming perspectives. Finally, we presented a timely and opportune review article focusing on the significant potential of CPC scaffolds for dental and craniofacial bone regeneration, which will be discussed thoroughly. CPC offers multiple capabilities that may be considered toward the oral defects, expecting a future outlook in nanotechnology design and performance.

Abstract Persisting apical periodontitis is a primary reason for multiple intervention in root canal. Persisting bacteria in root canal is related with the persisting infection. Despite the advancement in treatment strategies the persisting infection is a major challenge for endodontist. Here we tested two newly developed quaternary ammonium methacrylates (QAMs) against endodontic bacteria and their biofilms. Their antibacterial and antibiofilm efficiency were compared with chlorhexidine (CHX) and sodium hypochlorite (NaOCl). We measured the MIC, MBC and MBIC of DMADDM and DMAHDM respectively. We also detected the ratio of live/dead bacteria and bacterial composition in the biofilms treated by DMADDM and DMAHDM. We found that DMADDM and DMAHDM could inhibit the growth of bacteria and biofilms formation. The result showed that novel QAMs were remarkably efficient than CHX against biofilms. In addition, we found that Streptococcus gordonii (S. gordonii) and Enterococcus faecalis (E. faecalis) were frequent isolates after treatment with antimicrobial compounds.

The objective of this study was to develop novel modified giomers by incorporating the antibacterial quaternary ammonium monomers (QAMs), dimethylaminododecyl methacrylate (DMADDM) or dimethylaminohexadecyl methacrylate (DMAHDM) into a commercial giomer. The material performances including mechanical properties, surface characteristics, color data, cytotoxicity and fluoride release of the novel giomers were evaluated. Antibacterial activity against severe early childhood caries (S-ECC) saliva-derived biofilms was assessed by lactic acid production measurement, MTT assay, biofilm staining and 16S rRNA sequencing. A rat model was developed and the anti-caries effect was investigated by micro-CT scanning and modified Keyes’ scoring. The results showed that the material properties of the QAMs groups were comparable to those of the control group. The novel giomers significantly inhibited lactic acid production and biofilm viability of S-ECC saliva-derived biofilms. Furthermore, caries-related genera such as Streptococcus and Lactobacillus reduced in QAMs groups, which showed their potential to change the microbial compositions. In the rat model, lesion depth, mineral loss and scoring of the QAMs groups were significantly reduced, without side effects on oral tissues. In conclusion, the novel giomers incorporated with antibacterial QAMs could inhibit the cariogenic biofilms and help prevent secondary caries, with great potential for future application in restorative treatment.

Dimethacrylate-based resin composites restorations have become widely-used intraoral materials in daily dental practice. The increasing use of composites has greatly enhanced modern preventive and conservative dentistry. They have many superior features, especially esthetic properties, bondability, and elimination of mercury and galvanic currents. However, polymeric materials are highly susceptible to polymerization shrinkage and stresses that lead to microleakage, biofilm formation, secondary caries, and restoration loss. Several techniques have been investigated to minimize the side effects of these shrinkage stresses. The primary approach is through fabrications and modification of the resin matrices. Therefore, this review article focuses on the methods for testing the shrinkage, as well as formulations of resinous matrices available to reduce polymerization shrinkage and its associated stress. Furthermore, this article reviews recent cutting-edge developments on bioactive low-shrinkage-stress nanocomposites to effectively inhibit the growth and activities of cariogenic pathogens and enhance the remineralization process.

Bacterial persistence has become a worldwide health problem due to its ability to cause the recalcitrance and relapse of infections. The existence of bacterial persistence and their possible mechanisms have been widely reported. However, the following regrowth of persister cells is not clear although the awakening of dormant surviving persisters is the key to reinitialize bacterial infection. In this study, we investigated the growth character and cariogenic virulence during the recovery of Streptococcus mutans drug-tolerant persister cells induced by a novel quaternary ammonium: dimethylaminododecyl methacrylate (DMADDM). A remarkable lag phase was observed in S. mutans persisters when regrew at the first 24 h compared to normal cells. During the entire recovery state, persisters are metabolically active to increase the production of both water-soluble and water-insoluble glucan. The shortage of cell number in persisters resulted in the decrease of lactic acid production, but persisters gradually recovered the normal acid production ability after 72 h. The up-regulated expression of gtf and vicR was in line with comDE circuit and consistent with the virulence change during the regrowth stage. Our findings proved that lethal dosages of DMADDM induced drug-tolerant S. mutans persisters in biofilm, which had a prolonged lag phase and elevated cariogenic virulence during regrowth. The recovery and elevated virulence of persisters were regulated by quorum-sensing and VicRK pathway. This alarmed the elevated cariogenicity of persisters and highlighted the critical requirement for the drug-tolerance evaluation when developing new oral antimicrobial agents. To the best of our knowledge, we characterized the regrowth and cariogenic virulence variation of S. mutans persisters induced by quaternary ammonium for the first time. Our findings suggest that S. mutans persisters with the elevated cariogenic virulence during their regrowth stage highlighted the need of new strategy to overcome bacterial persistence. Meanwhile, the prolonged lag phase and the involvement of quorum-sensing system in the regrowth of S. mutans persisters may provide the potential targets.

Denture stomatitis is a multifactorial pathological condition of the oral mucosa that affects up to 72% of denture wearers. It is commonly seen on the palatal mucosa and characterized by erythema on the oral mucosa that are in contact with the denture surface. The aim of this study was to incorporate 2-methacryloyloxyethyl phosphorylcholine (MPC) and dimethylaminohexadecyl methacrylate (DMAHDM) into a high impact polymethylmethacrylate heat-cured denture base acrylic resin as a potential treatment for denture stomatitis. We used a comparative study design to examine the effect of incorporating MPC as a protein repellent agent and DMAHDM as an antifungal agent to prevent the adherence of Candida albicans to the denture base material. The dual incorporation of MPC and DMAHDM reduced C. albicans biofilm colony-forming unit by two orders of magnitude when compared to the control group devoid of the bioactive agents. Although the addition of MPC and DMAHDM alone or in combination significantly reduced the flexural strength of the material, they showed reduced roughness values when compared to control groups. This new denture acrylic resin provides the benefit of enhancing C. albicans biofilm elimination through dual mechanisms of action, which could potentially reduce the prevalence of denture stomatitis.

(1) Background: Vascularization remains a critical challenge in bone tissue engineering. The objective of this study was to prevascularize calcium phosphate cement (CPC) scaffold by co-culturing human periodontal ligament stem cells (hPDLSCs) and human umbilical vein endothelial cells (hUVECs) for the first time; (2) Methods: hPDLSCs and/or hUVECs were seeded on CPC scaffolds. Three groups were tested: (i) hUVEC group (hUVECs on CPC); (ii) hPDLSC group (hPDLSCs on CPC); (iii) co-culture group (hPDLSCs + hUVECs on CPC). Osteogenic differentiation, bone mineral synthesis, and microcapillary-like structures were evaluated; (3) Results: Angiogenic gene expressions of co-culture group were 6–9 fold those of monoculture. vWF expression of co-culture group was 3 times lower than hUVEC-monoculture group. Osteogenic expressions of co-culture group were 2–3 folds those of the hPDLSC-monoculture group. ALP activity and bone mineral synthesis of co-culture were much higher than hPDLSC-monoculture group. Co-culture group formed capillary-like structures at 14–21 days. Vessel length and junction numbers increased with time; (4) Conclusions: The hUVECs + hPDLSCs co-culture on CPC scaffold achieved excellent osteogenic and angiogenic capability in vitro for the first time, generating prevascularized networks. The hPDLSCs + hUVECs co-culture had much better osteogenesis and angiogenesis than monoculture. CPC scaffolds prevacularized via hPDLSCs + hUVECs are promising for dental, craniofacial, and orthopedic applications.

Orthodontic treatment is increasingly popular as people worldwide seek esthetics and better quality of life. In orthodontic treatment, complex appliances and retainers are placed in the patients’ mouths for at least one year, which often lead to biofilm plaque accumulation. This in turn increases the caries-inducing bacteria, decreases the pH of the retained plaque on an enamel surface, and causes white spot lesions (WSLs) in enamel. This article reviews the cutting-edge research on a new class of bioactive and therapeutic dental resins, cements, and adhesives that can inhibit biofilms and protect tooth structures. The novel approaches include the use of protein-repellent and anticaries polymeric dental cements containing 2-methacryloyloxyethyl phosphorylcholine (MPC) and dimethylaminododecyl methacrylate (DMAHDM); multifunctional resins that can inhibit enamel demineralization; protein-repellent and self-etching adhesives to greatly reduce oral biofilm growth; and novel polymethyl methacrylate resins to suppress oral biofilms and acid production. These new materials could reduce biofilm attachment, raise local biofilm pH, and facilitate the remineralization to protect the teeth. This novel class of dental resin with dual benefits of antibacterial and protein-repellent capabilities has the potential for a wide range of dental and biomedical applications to inhibit bacterial infection and protect the tissues.

Candida albicans (C. albicans) biofilm is a common etiological factor in denture stomatitis. The purpose of this study was to investigate the effects of incorporating 2-methacryloyloxyethyl phosphorylcholine (MPC) as a protein repellent into a new high-impact denture acrylic (HIPA) resin on the surface roughness, solution pH, and C. albicans biofilm adhesion to the denture base. The new acrylic denture resin base was formulated by mixing MPC into HIPA resin at mass fractions of 1.5%, 3%, and 4.5%. Surface roughness was measured using a Mitutoyo surface roughness tester. C. albicans biofilm growth and viability were assessed via colony forming unit counts. The pH of the biofilm growth medium was measured using a digital pH meter. Adding MPC to the HIPA resin at percentages of 1.5% and 3% increased the roughness values significantly (p < 0.05), while adding 4.5% MPC resulted in no difference in roughness values to that of the control group (p > 0.05). All experimental groups demonstrated neutral pH values (pH ≅ 7) and were not significantly different from each other (p > 0.05). Incorporating 2-methacryloyloxyethyl phosphorylcholine at 4.5% resulted in a significant (≅1 log) colony-forming unit reduction compared with the control group with 0% MPC (p < 0.05). A fungal-retarding denture acrylic resin was developed through the incorporation of MPC for its protein-repelling properties. This newly developed denture acrylic material has the potential to prevent oral microbial infections, such as denture stomatitis.

Polyetheretherketone (PEEK) is an important high-performance thermoplastic. Its excellent strength, stiffness, toughness, fatigue resistance, biocompatibility, chemical stability and radiolucency have made PEEK attractive in dental and orthopedic applications. However, PEEK has an inherently hydrophobic and chemically inert surface, which has restricted its widespread use in clinical applications, especially in bonding with dental resin composites. Cutting edge research on novel methods to improve PEEK applications in dentistry, including oral implant, prosthodontics and orthodontics, is reviewed in this article. In addition, this article also discusses innovative surface modifications of PEEK, which are a focus area of active investigations. Furthermore, this article also discusses the necessary future studies and clinical trials for the use of PEEK in the human oral environment to investigate its feasibility and long-term performance.

Decays in the roots of teeth is prevalent in seniors as people live longer and retain more of their teeth to an old age, especially in patients with periodontal disease and gingival recession. The objectives of this study were to develop a biocompatible nanocomposite with nano-sized calcium fluoride particles (Nano-CaF2), and to investigate for the first time the effects on osteogenic and cementogenic induction of periodontal ligament stem cells (hPDLSCs) from human donors.Nano-CaF2 particles with a mean particle size of 53 nm were produced via a spray-drying machine.Nano-CaF2 was mingled into the composite at 0%, 10%, 15% and 20% by mass. Flexural strength (160 ± 10) MPa, elastic modulus (11.0 ± 0.5) GPa, and hardness (0.58 ± 0.03) GPa for Nano-CaF2 composite exceeded those of a commercial dental composite (p < 0.05). Calcium (Ca) and fluoride (F) ions were released steadily from the composite. Osteogenic genes were elevated for hPDLSCs growing on 20% Nano-CaF2. Alkaline phosphatase (ALP) peaked at 14 days. Collagen type 1 (COL1), runt-related transcription factor 2 (RUNX2) and osteopontin (OPN) peaked at 21 days. Cementogenic genes were also enhanced on 20% Nano-CaF2 composite, promoting cementum adherence protein (CAP), cementum protein 1 (CEMP1) and bone sialoprotein (BSP) expressions (p < 0.05). At 7, 14 and 21 days, the ALP activity of hPDLSCs on 20% Nano-CaF2 composite was 57-fold, 78-fold, and 55-fold greater than those of control, respectively (p < 0.05). Bone mineral secretion by hPDLSCs on 20% Nano-CaF2 composite was 2-fold that of control (p < 0.05). In conclusion, the novel Nano-CaF2 composite was biocompatible and supported hPDLSCs. Nano-CaF2 composite is promising to fill tooth root cavities and release Ca and F ions to enhance osteogenic and cementogenic induction of hPDLSCs and promote periodontium regeneration.

Caries-related biofilms and associated complications are significant threats in dentistry, especially when biofilms grow over dental restorations. The inhibition of cariogenic biofilm associated with the onset of carious lesions is crucial for preventing disease recurrence after treatment. This in vitro study defined optimized parameters for using a photosensitizer, toluidine blue O (TBO), activated via a red light-emitting diode (LED)-based wireless device to control the growth of cariogenic biofilms. The effect of TBO concentrations (50, 100, 150, and 200 μg/mL) exposed to light or incubated in the dark was investigated in successive cytotoxicity assays. Then, a mature Streptococcus mutans biofilm model under sucrose challenge was treated with different TBO concentrations (50, 100, and 150 μg/mL), different light energy doses (36, 108, and 180 J/cm2), and different incubation times before irradiation (1, 3, and 5 min). The untreated biofilm, irradiation with no TBO, and TBO incubation with no activation represented the controls. After treatments, biofilms were analyzed via S. mutans colony-forming units (CFUs) and live/dead assay. The percentage of cell viability was within the normal range compared to the control when 50 and 100 μg/mL of TBO were used. Increasing the TBO concentration and energy dose was associated with biofilm inhibition (p < 0.001), while increasing incubation time did not contribute to bacterial elimination (p > 0.05). Irradiating the S. mutans biofilm via 100 μg/mL of TBO and ≈180 J/cm2 energy dose resulted in ≈3-log reduction and a higher amount of dead/compromised S. mutans colonies in live/dead assay compared to the control (p < 0.001). The light energy dose and TBO concentration optimized the bacterial elimination of S. mutans biofilms. These results provide a perspective on the determining parameters for highly effective photo-killing of caries-related biofilms and display the limitations imposed by the toxicity of the antibacterial photodynamic therapy’s chemical components. Future studies should support investigations on new approaches to improve or overcome the constraints of opportunities offered by photodynamic inactivation of caries-related biofilms.

The objectives were to investigate a novel combination of gene-knockout with antimicrobial dimethylaminohexadecyl methacrylate (DMAHDM) composite in regulating oral biofilm from a cariogenic state toward a non-cariogenic state. A tri-species biofilm model included cariogenic Streptococcus mutans (S. mutans), and non-cariogenic Streptococcus sanguinis (S. sanguinis) and Streptococcus gordonii (S. gordonii). Biofilm colony-forming-units (CFUs), lactic acid and polysaccharide production were measured. TaqMan real-time-polymerase-chain reaction was used to determine the percentage of each species in biofilm. The rnc gene-knockout for S. mutans with DMAHDM composite reduced biofilm CFU by five logs, compared to control (p < 0.05). Using parent S. mutans, an overwhelming S. mutans percentage of 68.99% and 69.00% existed in biofilms on commercial composite and 0% DMAHDM composite, respectively. In sharp contrast, with a combination of S. mutans rnc knockout and DMAHDM composite, the cariogenic S. mutans percentage in biofilm was reduced to only 6.33%. Meanwhile, the non-cariogenic S. sanguinis + S. gordonii percentage was increased to 93.67%. Therefore, combining rnc-knockout with bioactive and therapeutic dental composite achieved the greatest reduction in S. mutans, and the greatest increase in non-cariogenic species, thereby yielding the least lactic acid-production. This novel method is promising to obtain wide applications to regulate biofilms and inhibit dental caries.

Secondary caries often occurs at the tooth-composite margins. This study developed a novel bioactive composite containing DMAHDM (dimethylaminohexadecyl methacrylate) and NACP (nanoparticles of amorphous calcium phosphate), inhibiting caries at the enamel restoration margins in an in vitro saliva-derived biofilm secondary caries model for the first time. Four composites were tested: (1) Heliomolar nanocomposite, (2) 0% DMAHDM + 0% NACP, (3) 3% DMAHDM + 0% NACP, (D) 3% DMAHDM + 30% NACP. Saliva-derived biofilms were tested for antibacterial effects of the composites. Bovine enamel restorations were cultured with biofilms, Ca and P ion release of nanocomposite and enamel hardness at the enamel restoration margins was measured. Incorporation of DMAHDM and NACP into composite did not affect the mechanical properties (p > 0.05). The biofilms’ CFU (colony-forming units) were reduced by 2 logs via DMAHDM (p < 0.05). Ca and P ion release of the nanocomposite was increased at cariogenic low pH. Enamel hardness at the margins for DMAHDM group was 25% higher than control (p < 0.05). With DMAHDM + NACP, the enamel hardness was the greatest and about 50% higher than control (p < 0.05). Therefore, the novel composite containing DMAHDM and NACP was strongly antibacterial and inhibited enamel demineralization, resulting in enamel hardness at the margins under biofilms that approached the hardness of healthy enamel.

(1) Background: The objective of this study was to develop a novel dental nanocomposite containing dimethylaminohexadecyl methacrylate (DMAHDM), 2-methacryloyloxyethyl phosphorylcholine (MPC), and nanoparticles of calcium fluoride (nCaF2) for preventing recurrent caries via antibacterial, protein repellent and fluoride releasing capabilities. (2) Methods: Composites were made by adding 3% MPC, 3% DMAHDM and 15% nCaF2 into bisphenol A glycidyl dimethacrylate (Bis-GMA) and triethylene glycol dimethacrylate (TEGDMA) (denoted BT). Calcium and fluoride ion releases were evaluated. Biofilms of human saliva were assessed. (3) Results: nCaF2+DMAHDM+MPC composite had the lowest biofilm colony forming units (CFU) and the greatest ion release; however, its mechanical properties were lower than commercial control composite (p < 0.05). nCaF2+DMAHDM composite had similarly potent biofilm reduction, with mechanical properties matching commercial control composite (p > 0.05). Fluoride and calcium ion releases from nCaF2+DMAHDM were much more than commercial composite. Biofilm CFU on composite was reduced by 4 logs (n = 9, p < 0.05). Biofilm metabolic activity and lactic acid were also substantially reduced by nCaF2+DMAHDM, compared to commercial control composite (p < 0.05). (4) Conclusions: The novel nanocomposite nCaF2+DMAHDM achieved strong antibacterial and ion release capabilities, without compromising the mechanical properties. This bioactive nanocomposite is promising to reduce biofilm acid production, inhibit recurrent caries, and increase restoration longevity.

Polymeric materials are the first choice for restoring tooth cavities, bonding tooth-colored fillings, sealing root canal systems, and many other dental restorative applications. However, polymeric materials are highly susceptible to bacterial attachment and colonization, leading to dental diseases. Many approaches have been investigated to minimize the formation of biofilms over polymeric restorative materials and at the tooth/material interfaces. Among them, contact-killing compounds have shown promising results to inhibit dental biofilms. Contact-killing compounds can be immobilized within the polymer structure, delivering a long-lasting effect with no leaching or release, thus providing advantages compared to release-based materials. This review discusses cutting-edge research on the development of contact-killing compounds in dental restorative materials to target oral pathogens. Contact-killing compounds in resin composite restorations, dental adhesives, root canal sealers, denture-based materials, and crown cements have all demonstrated promising antibacterial properties. Contact-killing restorative materials have been found to effectively inhibit the growth and activities of several oral pathogens related to dental caries, periodontal diseases, endodontic, and fungal infections. Further laboratory optimization and clinical trials using translational models are needed to confirm the clinical applicability of this new generation of contact-killing dental restorative materials.

According to the American Dental Association Survey of Dental Services Rendered (published in 2007), 15 million root canal treatment procedures are performed annually. Endodontic therapy relies mainly on biomechanical preparation, chemical irrigation and intracanal medicaments which play an important role in eliminating bacteria in the root canal. Furthermore, adequate obturation is essential to confine any residual bacteria within the root canal and deprive them of nutrients. However, numerous studies have shown that complete elimination of bacteria is not achieved due to the complex anatomy of the root canal system. There are several conventional antibiotic materials available in the market for endodontic use. However, the majority of these antibiotics and antiseptics provide short-term antibacterial effects, and they impose a risk of developing antibacterial resistance. The root canal is a dynamic environment, and antibacterial and antibiofilm materials with long-term effects and nonspecific mechanisms of action are highly desirable in such environments. In addition, the application of acidic solutions to the root canal wall can alter the dentin structure, resulting in a weaker and more brittle dentin. Root canal sealers with bioactive properties come in direct contact with the dentin wall and can play a positive role in bacterial elimination and strengthening of the root structure. The new generation of nanostructured, bioactive, antibacterial and remineralizing additives into polymeric resin-based root canal sealers are discussed in this review. The effects of these novel bioactive additives on the physical and sealing properties, as well as their biocompatibility, are all important factors that are presented in this article.

Metformin is an old and widely accepted first-line drug for treating type 2 diabetes. Our previous studies demonstrate that metformin can stimulate the osteo/odontogenic differentiation of human-induced pluripotent stem cell-derived mesenchymal stem cells and human dental pulp cells (DPCs). Due to the rapid dilution of metformin from the defect area, the aim of this study was to develop a drug delivery system with controlled release of metformin to promote cell viability and odontogenic differentiation of DPCs favoring dentin regeneration. Calcium phosphate cement (CPC) containing chitosan and metformin as a scaffold was synthesized. DPCs were seeded onto the scaffold, and the viability and proliferation were evaluated at several time points. For osteogenic differentiation analysis, alkaline phosphatase (ALP) activity was tested, cells were stained with Alizarin Red, and the expression of odontogenic markers was evaluated by real-time polymerase chain reaction. DPCs remained viable and attached well to the CPC-chitosan composite scaffold. Moreover, the addition of metformin to the CPC-chitosan composite did not adversely affect cell proliferation, compared to that of CPC control. Our data further revealed that the novel CPC-chitosan-metformin composite enhanced the odontogenic differentiation of DPCs, as evidenced by higher ALP activity, elevated expression of odontoblastic markers, and strong mineral deposition. These results suggest that the new CPC-chitosan-metformin composite is a highly promising scaffold with the potential for tissue engineering applications including dentin regeneration.

Resin composites and adhesives are increasingly popular in dental restorations, but secondary caries is one of the main reasons for restoration failure. Quaternary ammonium monomers (QAMs) have an anti-microbial effect and are widely used in many fields. Since the concept of the immobilized antibacterial effect was put forward, dental restorations containing QAMs have been studied to reduce secondary caries. Previous studies have been struggling to develop novel anti-caries materials which might have triple benefits: good mechanical properties, antibacterial effects and remineralization potentials. Different kinds of QAMs have been proven to be effective in inhibiting the growth and metabolism of biofilms. Combination of QAMs and other nanoparticles in resin composites and adhesives could enhance their anti-caries capability. Therefore, QAMs are promising to show significant impact on the future of restorative and preventive dentistry.

Long-term heavy alcohol consumption could result in a range of health, social, and behavioral problems. People who abuse alcohol are at high risks of seriously having osteopenia, periodontal disease, and compromised oral health. However, the role of ethanol (EtOH) in the biological functions of human dental pulp cells (DPCs) is unknown. Whether EtOH affects the odontoblastic differentiation of DPCs through the mechanistic target of rapamycin (mTOR) remains unexplored. The objective of this study was to investigate the effects of EtOH on DPC differentiation and mineralization. DPCs were isolated and purified from human dental pulps. The proliferation and odontoblastic differentiation of DPCs treated with EtOH were subsequently investigated. Different doses of EtOH were shown to be cytocompatible with DPCs. EtOH significantly activated the mTOR pathway in a dose-dependent manner. In addition, EtOH downregulated the alkaline phosphatase activity, attenuated the mineralized nodule formation, and suppressed the expression of odontoblastic markers including ALP, DSPP, DMP-1, Runx2, and OCN. Moreover, the pretreatment with rapamycin, a specific mTOR inhibitor, markedly reversed the EtOH-induced odontoblastic differentiation and cell mineralization. Our findings show for the first time that EtOH can suppress DPC differentiation and mineralization in a mTOR-dependent manner, indicating that EtOH may be involved in negatively regulating the dental pulp repair.

Antibacterial bonding agents and composites containing dimethylaminododecyl methacrylate (DMADDM) have been recently developed. The objectives of this study were to investigate the antibacterial effect of novel adhesives containing different mass fractions of DMADDM on Streptococcus mutans (S. mutans) biofilm at different developmental stages. Different mass fractions of DMADDM were incorporated into adhesives and S. mutans biofilm at different developmetal stages were analyzed by MTT assays, lactic acid measurement, confocal laser scanning microscopy and scanning electron microscopy observations. Exopolysaccharides (EPS) staining was used to analyze the inhibitory effect of DMADDM on the biofilm extracellular matrix. Dentin microtensile strengths were also measured. Cured adhesives containing DMADDM could greatly reduce metabolic activity and lactic acid production during the development of S. mutans biofilms (p < 0.05). In earlier stages of biofilm development, there were no significant differences of inhibitory effects between the 2.5% DMADDM and 5% DMADDM group. However, after 72 h, the anti-biofilm effects of adhesives containing 5% DMADDM were significantly stronger than any other group. Incorporation of DMADDM into adhesive did not adversely affect dentin bond strength. In conclusion, adhesives containing DMADDM inhibited the growth, lactic acid production and EPS metabolism of S. mutans biofilm at different stages, with no adverse effect on its dentin adhesive bond strength. The bonding agents have the potential to control dental biofilms and combat tooth decay, and DMADDM is promising for use in a wide range of dental adhesive systems and restoratives.

Cariogenic oral biofilms are strongly linked to dental caries around dental sealants. Quaternary ammonium monomers copolymerized with dental resin systems have been increasingly explored for modulation of biofilm growth. Here, we investigated the effect of dimethylaminohexadecyl methacrylate (DMAHDM) on the cariogenic pathogenicity of Streptococcus mutans (S. mutans) biofilms. DMAHDM at 5 mass% was incorporated into a parental formulation containing 20 mass% nanoparticles of amorphous calcium phosphate (NACP). S. mutans biofilms were grown on the formulations, and biofilm inhibition and virulence properties were assessed. The tolerances to acid stress and hydrogen peroxide stress were also evaluated. Our findings suggest that incorporating 5% DMAHDM into 20% NACP-containing sealants (1) imparts a detrimental biological effect on S. mutans by reducing colony-forming unit counts, metabolic activity and exopolysaccharide synthesis; and (2) reduces overall acid production and tolerance to oxygen stress, two major virulence factors of this microorganism. These results provide a perspective on the value of integrating bioactive restorative materials with traditional caries management approaches in clinical practice. Contact-killing strategies via dental materials aiming to prevent or at least reduce high numbers of cariogenic bacteria may be a promising approach to decrease caries in patients at high risk.

Periodontitis is a prevalent infectious disease worldwide, causing the damage of periodontal support tissues, which can eventually lead to tooth loss. The goal of periodontal treatment is to control the infections and reconstruct the structure and function of periodontal tissues including cementum, periodontal ligament (PDL) fibers, and bone. The regeneration of these three types of tissues, including the re-formation of the oriented PDL fibers to be attached firmly to the new cementum and alveolar bone, remains a major challenge. This article represents the first systematic review on the cutting-edge researches on the regeneration of all three types of periodontal tissues and the simultaneous regeneration of the entire bone-PDL-cementum complex, via stem cells, bio-printing, gene therapy, and layered bio-mimetic technologies. This article primarily includes bone regeneration; PDL regeneration; cementum regeneration; endogenous cell-homing and host-mobilized stem cells; 3D bio-printing and generation of the oriented PDL fibers; gene therapy-based approaches for periodontal regeneration; regenerating the bone-PDL-cementum complex via layered materials and cells. These novel developments in stem cell technology and bioactive and bio-mimetic scaffolds are highly promising to substantially enhance the periodontal regeneration including both hard and soft tissues, with applicability to other therapies in the oral and maxillofacial region.

Demineralized dentin matrix (DDM), derived from human teeth, is an excellent scaffold material with exciting bioactive properties to enhance bone and dental tissue engineering efficacy. In this article, first the nano-structure and bioactive components of the dentin matrix were reviewed. Then the preparation methods of DDM and the resulting properties were discussed. Next, the efficacy of DDM as a bone substitute with in vitro and in vivo properties were analyzed. In addition, the applications of DDM in tooth regeneration with promising results were described, and the drawbacks and future research needs were also discussed. With the extraction of growth factors from DDM and the nano-structural properties of DDM, previous studies also broadened the use of DDM as a bioactive carrier for growth factor delivery. In addition, due to its excellent physical and biological properties, DDM was also investigated for incorporation into other biomaterials design and fabrication, yielding great enhancements in hard tissue regeneration efficacy.

Periodontitis is a common infectious disease characterized by loss of tooth-supporting structures, which eventually leads to tooth loss. The heavy burden of periodontal disease and its negative consequence on the patient’s quality of life indicate a strong need for developing effective therapies. According to the World Health Organization, 10–15% of the global population suffers from severe periodontitis. Advances in understanding the etiology, epidemiology and microbiology of periodontal pocket flora have called for antibacterial therapeutic strategies for periodontitis treatment. Currently, antimicrobial strategies combining with polymer science have attracted tremendous interest in the last decade. This review focuses on the state of the art of antibacterial polymer application against periodontal pathogens and biofilms. The first part focuses on the different polymeric materials serving as antibacterial agents, drug carriers and periodontal barrier membranes to inhibit periodontal pathogens. The second part reviews cutting-edge research on the synthesis and evaluation of a new generation of bioactive dental polymers for Class-V restorations with therapeutic effects. They possess antibacterial, acid-reduction, protein-repellent, and remineralization capabilities. In addition, the antibacterial photodynamic therapy with polymeric materials against periodontal pathogens and biofilms is also briefly described in the third part. These novel bioactive and therapeutic polymeric materials and treatment methods have great potential to inhibit periodontitis and protect tooth structures.

Cariogenic oral biofilms cause recurrent dental caries around composite restorations, resulting in unprosperous oral health and expensive restorative treatment. Quaternary ammonium monomers that can be copolymerized with dental resin systems have been explored for the modulation of dental plaque biofilm growth over dental composite surfaces. Here, for the first time, we investigated the effect of bis(2-methacryloyloxyethyl) dimethylammonium bromide (QADM) on human overlying mature oral biofilms grown intra-orally in human participants for 7⁻14 days. Seventeen volunteers wore palatal devices containing composite specimens containing 10% by mass of QADM or a control composite without QADM. After 7 and 14 days, the adherent biofilms were collected to determine bacterial counts via colony-forming unit (CFU) counts. Biofilm viability, chronological changes, and percentage coverage were also determined through live/dead staining. QADM composites caused a significant inhibition of Streptococcus mutans biofilm formation for up to seven days. No difference in the CFU values were found for the 14-day period. Our findings suggest that: (1) QADM composites were successful in inhibiting 1⁻3-day biofilms in the oral environment in vivo; (2) QADM significantly reduced the portion of the S. mutans group; and (3) stronger antibiofilm activity is required for the control of mature long-term cariogenic biofilms. Contact-killing strategies using dental materials aimed at preventing or at least reducing high numbers of cariogenic bacteria seem to be a promising approach in patients at high risk of the recurrence of dental caries around composites.

Polymeric tooth-colored restorations are increasingly popular in dentistry. However, restoration failures remain a major challenge, and more than 50% of all operative work was devoted to removing and replacing the failed restorations. This is a heavy burden, with the expense for restoring dental cavities in the U.S. exceeding $46 billion annually. In addition, the need is increasing dramatically as the population ages with increasing tooth retention in seniors. Traditional materials for cavity restorations are usually bioinert and replace the decayed tooth volumes. This article reviews cutting-edge research on the synthesis and evaluation of a new generation of bioactive dental polymers that not only restore the decayed tooth structures, but also have therapeutic functions. These materials include polymeric composites and bonding agents for tooth cavity restorations that inhibit saliva-based microcosm biofilms, bioactive resins for tooth root caries treatments, polymers that can suppress periodontal pathogens, and root canal sealers that can kill endodontic biofilms. These novel compositions substantially inhibit biofilm growth, greatly reduce acid production and polysaccharide synthesis of biofilms, and reduce biofilm colony-forming units by three to four orders of magnitude. This new class of bioactive and therapeutic polymeric materials is promising to inhibit tooth decay, suppress recurrent caries, control oral biofilms and acid production, protect the periodontium, and heal endodontic infections.

Dental sealants with antibacterial and remineralizing properties are promising for caries prevention among children and adolescents. The application of nanotechnology and polymer development have enabled nanoparticles of amorphous calcium phosphate (NACP) and dimethylaminohexadecyl methacrylate (DMAHDM) to emerge as anti-caries strategies via resin-based dental materials. Our objectives in this study were to (1) incorporate different mass fractions of NACP into a parental rechargeable and antibacterial sealant; (2) investigate the effects on mechanical performance, and (3) assess how the variations in NACP concentration would affect the calcium (Ca) and phosphate (PO4) ion release and re-chargeability over time. NACP were synthesized using a spray-drying technique and incorporated at mass fractions of 0, 10, 20 and 30%. Flexural strength, flexural modulus, and flowability were assessed for mechanical and physical performance. Ca and PO4 ion release were measured over 70 days, and three ion recharging cycles were performed for re-chargeability. The impact of the loading percentage of NACP upon the sealant’s performance was evaluated, and the optimized formulation was eventually selected. The experimental sealant at 20% NACP had flexural strength and flexural modulus of 79.5 ± 8.4 MPa and 4.2 ± 0.4 GPa, respectively, while the flexural strength and flexural modulus of a commercial sealant control were 70.7 ± 5.5 MPa (p > 0.05) and 3.3 ± 0.5 GPa (p < 0.05), respectively. A significant reduction in flow was observed in the experimental sealant at 30% NACP (p < 0.05). Increasing the NACP mass fraction increased the ion release. The sealant formulation with NACP at 20% displayed desirable mechanical performance and ideal flow and handling properties, and also showed high levels of long-term Ca and PO4 ion release and excellent recharge capabilities. The findings provide fundamental data for the development of a new generation of antibacterial and rechargeable Ca and PO4 dental sealants to promote remineralization and inhibit caries.

Dental caries is prevalent worldwide. Tooth cavity restorations cost more than $46 billion annually in the United States alone. The current generation of esthetic polymeric restorations have unsatisfactory failure rates. Replacing the failed restorations accounts for 50–70% of all the restorations. This article reviewed developments in producing a new generation of bioactive and therapeutic restorations. This includes: Protein-repellent and anti-caries polymeric dental composites, especially the use of 2-methacryloyloxyethyl phosphorylcholine (MPC) and dimethylaminododecyl methacrylate (DMAHDM); protein-repellent adhesives to greatly reduce biofilm acids; bioactive cements to inhibit tooth lesions; combining protein-repellency with antibacterial nanoparticles of silver; tooth surface coatings containing calcium phosphate nanoparticles for remineralization; therapeutic restorations to suppress periodontal pathogens; and long-term durability of bioactive and therapeutic dental polymers. MPC was chosen due to its strong ability to repel proteins. DMAHDM was selected because it had the most potent antibacterial activity when compared to a series of antibacterial monomers. The new generation of materials possessed potent antibacterial functions against cariogenic and periodontal pathogens, and reduced biofilm colony-forming units by up to 4 logs, provided calcium phosphate ions for remineralization and strengthening of tooth structures, and raised biofilm pH from a cariogenic pH 4.5 to a safe pH 6.5. The new materials achieved a long-term durability that was significantly beyond current commercial control materials. This new generation of bioactive and nanostructured polymers is promising for wide applications to provide therapeutic healing effects and greater longevity for dental restorations.