Cutting-edge filler technologies to release bio-active components for restorative and preventive dentistry.

Advancements in materials used for restorative and preventive treatment is being directed toward "bio-active" functionality. Incorporation of filler particles that release active components is a popular method to create bio-active materials, and many approaches are available to develop fillers with the ability to release components that provide "bio-protective" or "bio-promoting" properties; e.g. metal/calcium phosphate nanoparticles, multiple ion-releasing glass fillers, and non-biodegradable polymer particles. In this review paper, recent developments in cutting-edge filler technologies to release bio-active components are addressed and summarized according to their usefulness and functions, including control of bacterial infection, tooth strengthening, and promotion of tissue regeneration.

Novel nanomaterial-based antibacterial photodynamic therapies to combat oral bacterial biofilms and infectious diseases.

Oral diseases such as tooth caries, periodontal diseases, endodontic infections, etc., are prevalent worldwide. The heavy burden of oral infectious diseases and their consequences on the patients' quality of life indicates a strong need for developing effective therapies. Advanced understandings of such oral diseases, e.g., inflammatory periodontal lesions, have raised the demand for antibacterial therapeutic strategies, because these diseases are caused by viruses and bacteria. The application of antimicrobial photodynamic therapy (aPDT) on oral infectious diseases has attracted tremendous interest in the past decade. However, aPDT had a minimal effect on the viability of organized biofilms due to the hydrophobic nature of the majority of the photosensitizers (PSs). Therefore, novel nanotechnologies were rapidly developed to target the delivery of hydrophobic PSs into microorganisms for the antimicrobial performance improvement of aPDT. This review focuses on the state-of-the-art of nanomaterials applications in aPDT against oral infectious diseases. The first part of this article focuses on the cutting-edge research on the synthesis, toxicity, and therapeutic effects of various forms of nanomaterials serving as PS carriers for aPDT applications. The second part discusses nanomaterials applications for aPDT in treatments of oral diseases. These novel bioactive nanomaterials have demonstrated great potential to serve as carriers for PSs to substantially enhance the PDT therapeutic effects. Furthermore, the novel aPDT applications not only have exciting therapeutic potential to inhibit bacterial plaque-initiated oral diseases, but also have a wide applicability to other biomedical and tissue engineering applications.

Calcium phosphate cements for bone engineering and their biological properties.

Calcium phosphate cements (CPCs) 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. Much effort has been made to enhance the biological performance of CPCs, including their biocompatibility, osteoconductivity, osteoinductivity, biodegradability, bioactivity, and interactions with cells. This review article focuses on the major recent developments in CPCs, including 3D printing, injectability, stem cell delivery, growth factor and drug delivery, and pre-vascularization of CPC scaffolds via co-culture and tri-culture techniques to enhance angiogenesis and osteogenesis.

Quaternary ammonium-induced multidrug tolerant Streptococcus mutans persisters elevate cariogenic virulence in vitro.

Dental caries are the most prevalent chronic infections in the oral cavity, and Streptococcus mutans acts as the main cariogenic bacterial species. Antibacterial quaternary ammonium compounds (QAs) have been developed to preveFnt or treat dental caries. However, there is no report on the tolerance of S. mutans to QAs. In this study, we investigated the development of S. mutans persistence induced by a novel dental caries defensive agent, dimethylaminododecyl methacrylate (DMADDM), for the first time. Typical biphasic killing kinetics for persisters were observed in both S. mutans planktonic and biofilm cultures challenged by DMADDM at concentrations of 20 and 200 µg·mL-1, respectively. The persisters tolerated six other antibiotics with different antibacterial mechanisms, while only daptomycin and vancomycin could slightly reduce the persister numbers in planktonic cultures. The distribution of persisters in DMADDM-treated biofilms was similar to that in the untreated control, except that the total biomass and biofilm height were significantly reduced. A higher exopolysaccharides (EPS):bacteria ratio was observed in DMADDM-treated biofilms. Persisters in biofilms significantly upregulated gtf gene expression, indicating an increase in the bacteria's ability to produce EPS and an elevated capability of cariogenic virulence. Carbon source metabolism was significantly reduced, as related metabolic genes were all downregulated in persisters. Concentrations of 0.1 mM, 1 mM and 10 mM of extra glucose significantly reduced the number of persisters both in planktonic and biofilm conditions. The formation of non-inheritable and multidrug tolerant persisters induced by DMADDM suggested that drug tolerance and new persistent eradication strategies should be considered for oral antibacterial agents.

Novel rechargeable calcium phosphate nanoparticle-containing orthodontic cement.

White spot lesions (WSLs), due to enamel demineralization, occur frequently in orthodontic treatment. We recently developed a novel rechargeable dental composite containing nanoparticles of amorphous calcium phosphate (NACP) with long-term calcium (Ca) and phosphate (P) ion release and caries-inhibiting capability. The objectives of this study were to develop the first NACP-rechargeable orthodontic cement and investigate the effects of recharge duration and frequency on the efficacy of ion re-release. The rechargeable cement consisted of pyromellitic glycerol dimethacrylate (PMGDM) and ethoxylated bisphenol A dimethacrylate (EBPADMA). NACP was mixed into the resin at 40% by mass. Specimens were tested for orthodontic bracket shear bond strength (SBS) to enamel, Ca and P ion initial release, recharge and re-release. The new orthodontic cement exhibited an SBS similar to commercial orthodontic cement without CaP release (P>0.1). Specimens after one recharge treatment (e.g., 1 min immersion in recharge solution repeating three times in one day, referred to as "1 min 3 times") exhibited a substantial and continuous re-release of Ca and P ions for 14 days without further recharge. The ion re-release did not decrease with increasing the number of recharge/re-release cycles (P>0.1). The ion re-release concentrations at 14 days versus various recharge treatments were as follows: 1 min 3 times>3 min 2 times>1 min 2 times>6 min 1 time>3 min 1 time>1 min 1 time. In conclusion, although previous studies have shown that NACP nanocomposite remineralized tooth lesions and inhibited caries, the present study developed the first orthodontic cement with Ca and P ion recharge and long-term release capability. This NACP-rechargeable orthodontic cement is a promising therapy to inhibit enamel demineralization and WSLs around orthodontic brackets.

Primer containing dimethylaminododecyl methacrylate kills bacteria impregnated in human dentin blocks.

Antibacterial dimethylaminododecyl methacrylate (DMADDM) was recently synthesized. The objectives of this study were to: (1) investigate antibacterial activity of DMADDM-containing primer on Streptococcus mutans impregnated into dentin blocks for the first time, and (2) compare the antibacterial efficacy of DMADDM with a previous quaternary ammonium dimethacrylate (QADM). Scotchbond Multi-Purpose (SBMP) bonding agent was used. DMADDM and QADM were mixed into SBMP primer. Six primers were tested: SBMP control primer P, P+2.5% DMADDM, P+5% DMADDM, P+7.5% DMADDM, P+10% DMADDM, and P+10% QADM. S. mutans were impregnated into human dentin blocks, and each primer was applied to dentin to test its ability to kill bacteria in dentinal tubules. Bacteria in dentin were collected via a sonication method, and the colony-forming units (CFU) and inhibition zones were measured. The bacterial inhibition zone of P+10% DMADDM was 10 times that of control primer (P<0.05). CFU in dentin with P+10% DMADDM was reduced by three orders of magnitude, compared with control. DMADDM had a much stronger antibacterial effect than QADM, and antibacterial efficacy increased with increasing DMADDM concentration. Dentin shear bond strengths were similar among all groups (P>0.1). In conclusion, antibacterial DMADDM-containing primer was validated to kill bacteria inside dentin blocks, possessing a much stronger antibacterial potency than the previous QADM. DMADDM-containing bonding agent was effective in eradicating bacteria in dentin, and its efficacy was directly proportional to DMADDM mass fraction. Therefore, DMADDM may be promising for use in bonding agents as well as in other restorative and preventive materials to inhibit bacteria.

Effect of anti-biofilm glass-ionomer cement on Streptococcus mutans biofilms.

Dental restorative materials with antimicrobial properties can inhibit bacterial colonization, which may result in a reduction of caries at tooth-filling interaction zones. This study aimed to develop antibacterial glass-ionomer cements (GIC) containing a quaternary ammonium monomer (dimethylaminododecyl methacrylate, DMADDM), and to investigate their effect on material performance and antibacterial properties. Different mass fractions (0, 1.1% and 2.2%) of DMADDM were incorporated into the GIC. The flexure strength, surface charge density, surface roughness and fluoride release were tested. A Streptococcus mutans biofilm model was used. Exopolysaccharides (EPS) staining was used to analyze the inhibitory effect of DMADDM on the biofilm matrix. In addition, biofilm metabolic activity, lactic acid metabolism and the expression of glucosyltransferase genes gtfB, gtfC and gtfD were measured. GIC containing 1.1% and 2.2% DMADDM had flexural strengths matching those of the commercial control (P>0.1). DMADDM was able to increase the surface charge density but reduced surface roughness (P<0.05). The incorporation of 1.1% and 2.2% DMADDM elevated the release of fluoride by the GIC in the first 2 days (P<0.05). The novel DMADDM-modified GIC significantly reduced biofilm metabolic activity (P<0.05) and decreased lactic acid production (P<0.05). The quantitative polymerase chain reaction (qPCR) results showed that the expression of gtfB, gtfC and gtfD decreased when mass fractions of DMADDM increased (P<0.05). EPS staining showed that both the bacteria and EPS in biofilm decreased in the DMADDM groups. The incorporation of DMADDM could modify the properties of GIC to influence the development of S. mutans biofilms. In this study, we investigated the interface properties of antibacterial materials for the first time. GIC containing DMADDM can improve material performance and antibacterial properties and may contribute to the better management of secondary caries.

A novel protein-repellent dental composite containing 2-methacryloyloxyethyl phosphorylcholine.

Secondary caries due to biofilm acids is a primary cause of dental composite restoration failure. To date, there have been no reports of dental composites that can repel protein adsorption and inhibit bacteria attachment. The objectives of this study were to develop a protein-repellent dental composite by incorporating 2-methacryloyloxyethyl phosphorylcholine (MPC) and to investigate for the first time the effects of MPC mass fraction on protein adsorption, bacteria attachment, biofilm growth, and mechanical properties. Composites were synthesized with 0 (control), 0.75%, 1.5%, 2.25%, 3%, 4.5% and 6% of MPC by mass. A commercial composite was also tested as a control. Mechanical properties were measured in three-point flexure. Protein adsorption onto the composite was determined by the microbicinchoninic acid method. A human saliva microcosm biofilm model was used. Early attachment at 4 h, biofilm at 2 days, live/dead staining and colony-forming units (CFUs) of biofilms grown on the composites were investigated. Composites with MPC of up to 3% had mechanical properties similar to those without MPC and those of the commercial control, whereas 4.5% and 6% MPC decreased the mechanical properties (P<0.05). Increasing MPC from 0 to 3% reduced the protein adsorption on composites (P<0.05). The composite with 3% MPC had protein adsorption that was 1/12 that of the control (P<0.05). Oral bacteria early attachment and biofilm growth were also greatly reduced on the composite with 3% MPC, compared to the control (P<0.05). In conclusion, incorporation of MPC into composites at 3% greatly reduced protein adsorption, bacteria attachment and biofilm CFUs, without compromising mechanical properties. Protein-repellent composites could help to repel bacteria attachment and plaque build-up to reduce secondary caries. The protein-repellent method might be applicable to other dental materials.