Novel antibacterial titanium implant healing abutment with dimethylaminohexadecyl methacrylate to combat implant-related infections.

OBJECTIVE: Implant-related infections from the adhesion and proliferation of dental plaque are a major challenge for dental implants. The objectives of this study were to: (1) develop novel antibacterial titanium (Ti) healing abutment; (2) investigate the inhibition of implant infection-related pathogenic bacteria and saliva-derived biofilm, and evaluate the biocompatibility of the new material for the first time. METHODS: Dimethylaminohexadecyl methacrylate (DMAHDM) and hydroxyapatite (HAP) were polymerized via polydopamine (PDA) on Ti. Staphylococcus aureus (S. aureus), Streptococcus sanguinis (S. sanguinis) and human saliva-derived biofilms were tested. After 4 weeks of DMAHDM release, the antibacterial efficacy of the DMAHDM remaining on Ti surface and the DMADHM in medium was tested. Biocompatibility was determined using human gingival fibroblasts (HGFs) and periodontal ligament stem cells (PDLSCs). RESULTS: The DMAHDM-loaded coating filled into the nano-voids in Ti surfaces. The modified Ti showed potent antibacterial activity, reducing the CFU of S. aureus, S. sanguinis and saliva-derived biofilms by 8, 7 and 4 log, respectively (P < 0.05). After 4 weeks of release, the modified Ti was still able to reduce S. aureus and S. sanguinis biofilm CFU by 1-3 log (P < 0.05). This provided strong antibacterial function for more than 4 weeks, which were the high-risk period for implant infections. The new material showed excellent biocompatibility when compared to control (P > 0.05). CONCLUSION: Novel DMAHDM-loaded Ti healing abutment had strong antibacterial effects, reducing biofilm CFUs by orders of magnitude, and lasting for over four weeks to cover the high-risk period for implant infections. The novel antibacterial Ti is promising to combat implant-related infections in dental, craniofacial and orthopedic applications.

pH-responsive DMAEM Monomer for dental caries inhibition.

Previous research indicated that there is an aggregate of microorganism in oral cavity which takes part in promoting the occurrence of dental caries, but few studies on anticaries materials for these 'core microbiome' were developed. And We've found that DMAEM monomer has an obvious inhibitory effect on the growth of Streptococcus mutans and saliva biofilm, but the effect of that on the "core microbiome" of caries need further research. Thus, the objectives of this study were to explore the effect of DMAEM monomer on the core microbiota of dental caries, and to further study its anticaries effect. The changes of microbial structure and metabolic activity of the core microbiota biofilm were detected through measuring lactic acid yield, viable bacteria counts and demineralization depth, et al., and the anticaries potential in vivo of DMAEM monomer was evaluated by rat caries model. Meanwhile, high-throughput sequencing was used to analyze the microbial diversity change of saliva samples of rats. The results showed that DMAEM monomer could inhibit the growth of the core microbiota biofilm, decrease the metabolic activity and the acid production, as well as reduce the ability of demineralization under acidic conditions. Moreover, the degree of caries in the DMAEM group was significantly reduced, and the diversity and the evenness of oral microecology in the rats were statistically higher. In summary, DMAEM monomer could respond to acidic environment, significantly inhibit the cariogenic ability of the 'core microbiome' of caries, and help to maintain the microecological balance of oral cavity.

Novel dental resin infiltrant containing smart monomer dodecylmethylaminoethyl methacrylate.

Objectives: White 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. Methods: DMAEM 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. Result: DMAEM 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). Significance: A 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.

Effects of a Novel, Intelligent, pH-Responsive Resin Adhesive on Cariogenic Biofilms In Vitro.

Background: Secondary caries often result in a high failure rate of resin composite restoration. Herein, we studied the dodecylmethylaminoethyl methacrylate−modified resin adhesive (DMAEM@RA) to investigate its pH-responsive antimicrobial effect on Streptococcus mutans and Candida albicans dual-species biofilms and on secondary caries. Methods: Firstly, the pH-responsive antimicrobial experiments including colony-forming units, scanning electron microscopy and exopoly-saccharide staining were measured. Secondly, lactic acid measurement and transverse microradiography analysis were performed to determine the preventive effect of DMAEM@RA on secondary caries. Lastly, quantitative real-time PCR was applied to investigate the antimicrobial effect of DMAEM@RA on cariogenic virulence genes. Results: DMAEM@RA significantly inhibited the growth, EPS, and acid production of Streptococcus mutans and Candida albicans dual-species biofilms under acidic environments (p < 0.05). Moreover, at pH 5 and 5.5, DMAEM@RA remarkably decreased the mineral loss and lesion depth of tooth hard tissue (p < 0.05) and down-regulated the expression of cariogenic genes, virulence-associated genes, and pH-regulated genes of dual-species biofilms (p < 0.05). Conclusions: DMAEM@RA played an antibiofilm role on Streptococcus mutans and Candida albicans dual-species biofilms, prevented the demineralization process, and attenuated cariogenic virulence in a pH-dependent manner.

Novel Giomers Incorporated with Antibacterial Quaternary Ammonium Monomers to Inhibit Secondary Caries.

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.

Novel dental implant modifications with two-staged double benefits for preventing infection and promoting osseointegration in vivo and in vitro.

Peri-implantitis are a major problem causing implant failure these days. Accordingly, anti-infection during the early stage and subsequent promotion of osseointegration are two main key factors to solve this issue. Micro-arc oxidation (MAO) treatment is a way to form an oxidation film on the surface of metallic materials. The method shows good osteogenic properties but weak antibacterial effect. Therefore, we developed combined strategies to combat severe peri-implantitis, which included the use of a novel compound, PD, comprising dendrimers poly(amidoamine) (PAMAM) loading dimethylaminododecyl methacrylate (DMADDM) as well as MAO treatment. Here, we explored the chemical properties of the novel compound PD, and proved that this compound was successfully synthesized, with the loading efficiency and encapsulation efficiency of 23.91% and 31.42%, respectively. We further report the two-stage double benefits capability of PD + MAO: (1) in the first stage, PD + MAO could decrease the adherence and development of biofilms by releasing DMADDM in the highly infected first stage after implant surgery both in vitro and in vivo; (2) in the second stage, PD + MAO indicated mighty anti-infection and osteoconductive characteristics in a rat model of peri-implantitis in vivo. This study first reports the two-staged, double benefits of PD + MAO, and demonstrates its potential in clinical applications for inhibiting peri-implantitis, especially in patients with severe infection risk.

Stimuli-responsive drug delivery systems for head and neck cancer therapy.

Head and neck cancer (HNC) is among the most common malignancy that has a profound impact on human health and life quality. The treatment for HNC, especially for the advanced cancer is stage-dependent and in need of combined therapies. Various forms of adjuvant treatments such as chemotherapy, phototherapy, hyperthermia, gene therapy have been included in the HNC therapy. However, there are still restrictions with traditional administration such as limited in situ therapeutic effect, systemic toxicity, drug resistance, etc. In recent years, stimuli-responsive drug delivery systems (DDSs) have attracted the great attention in HNC therapy. These intelligent DDSs could respond to unique tumor microenvironment, external triggers or dual/multi stimulus with more specific drug delivery and release, leading to enhanced treatment efficiency and less reduced side effects. In this article, recent studies on stimuli-responsive DDSs for HNC therapy were summarized, which could respond to endogenous and exogenous triggers including pH, matrix metalloproteinases (MMPs), reactive oxygen species (ROS), redox condition, light, magnetic field and multi stimuli. Their therapeutic remarks, current limits and future prospect for these intelligent DDSs were discussed. Furthermore, multifunctional stimuli-responsive DDSs have also been reviewed. With the modification of drug carriers or co-loading with therapeutic agents. Those intelligent DDSs showed more biofunctions such as combined therapeutic effects or integration of diagnosis and treatment for HNC. It is believed that stimuli-responsive drug delivery systems showed great potential for future clinic translation and application for the treatment of HNC.

Anti-caries effect of resin infiltrant modified by quaternary ammonium monomers.

OBJECTIVES: Resin infiltrant is used in early enamel caries. However, commercial resin infiltrant lacks persistent antibacterial activity. Dimethylaminododecyl methacrylate (DMADDM) was added to resin infiltrant to give it sustainable antibacterial properties and inhibit demineralization. METHODS: After the application of resin infiltrant to bovine enamel, cytotoxicity, surface roughness, and aesthetics were assessed. A multi-species biofilm was incubated on the enamel disk before and one month after microbial-aging. After a 48-h anaerobic incubation, biomass accumulation, metabolic activity, and lactic acid were analyzed using a crystal violet assay, an MTT (3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, and a lactic acid assay. Biofilm structure and composition were determined by live/dead staining, exopolysaccharide (EPS) staining, scanning electron microscopy (SEM), and quantitative polymerase chain reaction (qPCR). The depth and content of demineralization were tested by transverse microradiography (TMR). RESULTS: Incorporating DMADDM did not increase the cytotoxicity or change the physical properties when the mass fraction of the DMADDM was 2.5-10 %. The modification decreased the amount of bacterial biofilm, metabolic activity, lactic acid production, EPS, and the proportion of Streptococcus mutans in the biofilms. It also provided anti-demineralization effects. The surface roughness and antibacterial ability were not changed after one month of microbial-aging. CONCLUSION: The incorporation of DMADDM improved the antibacterial and anti-demineralization effects of the material. It demonstrated a sustained antibacterial effect. CLINICAL SIGNIFICANCE: The antibacterial modification might be a potential choice for future clinical applications to inhibit early enamel caries.

Emerging Applications of Drug Delivery Systems in Oral Infectious Diseases Prevention and Treatment.

The oral cavity is a unique complex ecosystem colonized with huge numbers of microorganism species. Oral cavities are closely associated with oral health and sequentially with systemic health. Many factors might cause the shift of composition of oral microbiota, thus leading to the dysbiosis of oral micro-environment and oral infectious diseases. Local therapies and dental hygiene procedures are the main kinds of treatment. Currently, oral drug delivery systems (DDS) have drawn great attention, and are considered as important adjuvant therapy for oral infectious diseases. DDS are devices that could transport and release the therapeutic drugs or bioactive agents to a certain site and a certain rate in vivo. They could significantly increase the therapeutic effect and reduce the side effect compared with traditional medicine. In the review, emerging recent applications of DDS in the treatment for oral infectious diseases have been summarized, including dental caries, periodontitis, peri-implantitis and oral candidiasis. Furthermore, oral stimuli-responsive DDS, also known as "smart" DDS, have been reported recently, which could react to oral environment and provide more accurate drug delivery or release. In this article, oral smart DDS have also been reviewed. The limits have been discussed, and the research potential demonstrates good prospects.

The anti-caries effects of dental adhesive resin influenced by the position of functional groups in quaternary ammonium monomers.

OBJECTIVES: A new quaternary ammonium monomer (QAM), triethylaminododecyl acrylate (TEADDA) was synthesized, in which the position of the functional groups was different from that of dimethylaminododecyl methacrylate (DMADDM). The objectives were to: (1) investigate the effect of the changed position of the functional groups on the mechanical properties, anti-biofilm activity and biocompatibility of adhesive resin, and (2) study the anti-bacterial mechanism of QAM to improve the performance of the adhesive system modified by QAM. METHODS: TEADDA and DMADDM were added into adhesives. Microtensile bond strength and surface charge density were measured. Multi-species biofilms were incubated on specimens for 16h, 48h and 72h and analyzed via MTT assay, lactic acid measurement and confocal laser scanning microscopy. The ratio of different species of bacteria was measured by real-time polymerase chain reaction. Cytotoxicity and biocompatibility were analyzed by eluents cytotoxicity test and histological images of H&E staining via an animal study in rats. RESULTS: The mass fraction of TEDDA allowed to be added into adhesive was higher than that of DMADDM. However, even 10% TEADDA did not yield a strong anti-biofilm effect on biofilm growth, lactic acid production and bacteria compositions. TEADDA added into adhesives showed better mechanical properties but weaker anti-bacterial effect. There was no significant difference on cytotoxicity and biocompatibility between DMADDM and TEADDA. SIGNIFICANCE: The study could be helpful for the investigation of the anti-caries mechanism of QAMs, the design of new QAMs and the improvement of the anti-caries activity of the modified dental materials.