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The objectives of this in vitro study were to develop a novel low-shrinkage-stress flowable nanocomposite with antibacterial properties through the incorporation of dimethylaminohexadecyl methacrylate (DMAHDM) and nanoparticles of amorphous calcium phosphate (NACP), and investigate the mechanical and oral biofilm properties, to be used in minimally-invasive techniques. The light-cured low-shrinkage-stress flowable resin was formulated by mixing urethane dimethacrylate (UDMA) and triethylene glycol divinylbenzyl ether (TEG-DVBE) at a 1:1 mass ratio. Different mass fractions of glass, and either 5% DMAHDM or 20%NACP or both were incorporated. Paste flowability, ultimate micro tensile strength and surface roughness were evaluated. The antibacterial response of DMAHDM resin was assessed by using biofilms of human saliva-derived microcosm model. Virtuoso flowable composite was used as a control. (45% resin+5% DMAHDM+20% NACP+30% glass) formula yielded the needed outcomes. It had flow rate within the range of ISO requirement. The micro tensile strength was (39.1 ± 4.3) MPa, similar to (40.1 ± 4.0) MPa for commercial control (p > 0.05). The surface roughness values of the novel composite (0.079 ± 0.01) µm similar to commercial composite (0.09 ± 0.02) µm (p > 0.05). Salivary microcosm biofilm colony forming unit values were reduced by 5–6 logs (p < 0.05). Biofilm metabolic activity was also substantially reduced, compared to control composite (p < 0.05). The novel bioactive flowable nanocomposite achieved strong antibacterial activities without compromising the mechanical properties. It is promising to be used as pit and fissure sealants, and as fillings in conservative cavities to inhibit recurrent caries and increase restoration longevity. [ABSTRACT FROM AUTHOR]

Nine antibacterial di-methacrylate monomers based on bis-quaternary ammonium salts (bis-QAMs) were synthesized and structurally characterized. The biological activity of the bis-QAMs was tested in terms of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) on different bacterial strains achieving promising results and, in most cases, a complete bactericidal effect using a bis-QAM concentration lower than 1 mg/mL. Two of the structures showed comparable and superior activity against S. mutans than the commercial monomer 12-methacryloyloxydodecyl pyridinium bromide (MDBP). All the bis-QAMs here described were able to inhibit S. mutans biofilm formation at a concentration equal to the MIC value. From the analysis of the obtained data, some correlation regarding the structure and the antibacterial activity of the bis-QAMs could be drawn: a flexible alkyl C 12 spacer between the two quaternary ammonium moieties increased the monomer antibacterial effect in comparison to the aromatic ones; the equilibrium between hydrophobic and hydrophilic moieties was directly correlated to the bactericidal range of action; the increase of the steric hindrance of the ammonium side groups might be both advantageous or disadvantageous to the antibacterial efficacy depending on the whole monomer chemical structure. Even though the possible correlation between the monomer structures and their bacteriostatic or bactericidal effect is under investigation, the monomers exhibited low cytotoxicity on human dental pulp stem cells, confirming their promising potential in the dental materials' field. The use of dental resins with antibacterial monomers might prevent the formation of secondary caries at the restoration margins. For this purpose, a series of di-methacrylate bis-quaternary ammonium monomers (QAMs) was developed. Unlike antibacterial mono-methacrylate monomers already described in the literature, the synthesized di-methacrylate monomers have the potential of acting as cross-linkers stabilizing the polymeric network and bear two quaternary ammonium groups that increase their antibacterial ability. The QAMs exert bactericidal activity on both Gram(+) and Gram(−) bacterial strains maintaining at the same time good biocompatibility with the oral environment. Some structural elements of the monomers were clearly related to high antibacterial properties, and this can help design new active structures and better understand their mechanism of action. [Display omitted] [ABSTRACT FROM AUTHOR]

Hydrolytic and enzymatic degradation of resin adhesives over time has been mainly attributed to secondary caries formation of methacrylate-based tooth-colored resin-based composite restorations. Ability of resin adhesive monomers to infiltrate into demineralized dentin forming stiff polymer matrix and potentially bonding to tooth structure is also a crucial property. The only commercially available antibacterial monomer, 12-methacryloyloxydodecyl pyridinium bromide (MDPB), is a quaternary ammonium methacrylate. This methacrylate monomer undergoes hydrolytic degradation, and could not bond to tooth structure. In this study, a new hydrolytic resistant monomer HMTAF was synthesized. It is methacrylamide-based monomer that, unlike methacrylate, is highly resistant to hydrolysis. Its molecular structure has particular functional groups; quaternary ammonium fluoride salt with potential antibacterial fluoride-releasing activity, hydroxyl and amide group with hydrogen bonding potential to dentin collagen. Hydroxyl group also increases monomer hydrophilicity for better penetration into water-saturated dentin and sufficient resin-dentin bond. The synthesized HMTAF and its polymer showed no hydrolytic degradation in acidic environment, while MDPB and its polymer were partially decomposed under this challenge. The conversion of monomer HMTAF to polymer was illustrated by FT-IR. The results indicated that HMTAF is highly resistant to hydrolysis, polymerizable and non-cytotoxic to Vero cell lines. It is a potential monomer to be incorporated into resin adhesives for improving hydrolytic and enzymatic resistance.

Purpose: To evaluate the marginal adaptation of mixed Class V cavities restored with Clearfil Protect Bond (Kuraray), Clearfil SE Bond (Kuraray), and two experimental combinations of both marketed adhesives, after fatigue and water storage. Materials and Methods: Four groups (Clearfil Protect Bond, Clearfil SE Bond, Exp. 1 and Exp. 2) of Class V cavities were restored with a microhybrid restorative composite (Clearfil APX, Kuraray). The marginal quality of these restorations was quantified by evaluation of gold-coated epoxy replicas with scanning electron microscopy before loading, after loading, and after a 12-month period of water storage. Data from marginal adaptation along the total margin length, on enamel, and on dentin were analyzed with the Wilcoxon signed rank test for differences within a group and with Kruskal-Wallis in order to assess the differences between groups. The Bonferroni test was used for post-hoc comparisons, and the confidence level was set to 95%. Results: The mean percentages (±SD) of "continuous margin" of the total marginal length ranged from 79.5% (±13.3) to 62.2% (±10.4) and from 70% (±11) to 61% (±15.1) after loading and after storage, respectively. No significant differences could be detected among the different groups. However, the marginal adaptation of Clearfil Protect Bond remained the most stable of all materials tested, as no significant differences were detected between the percentages of continuous margins before loading, after loading, or after storage. Conclusions: The use of an antibacterial adhesive system was as effective as the conventional two-step self-etching adhesive in the marginal adaptation of Class V restorations. [ABSTRACT FROM AUTHOR]

Hydrolytic and enzymatic degradation of resin adhesives over time has been mainly attributed to secondary caries formation of methacrylate-based tooth-colored resin-based composite restorations. Ability of resin adhesive monomers to infiltrate into demineralized dentin forming stiff polymer matrix and potentially bonding to tooth structure is also a crucial property. The only commercially available antibacterial monomer, 12-methacryloyloxydodecyl pyridinium bromide (MDPB), is a quaternary ammonium methacrylate. This methacrylate monomer undergoes hydrolytic degradation, and could not bond to tooth structure. In this study, a new hydrolytic resistant monomer HMTAF was synthesized. It is methacrylamide-based monomer that, unlike methacrylate, is highly resistant to hydrolysis. Its molecular structure has particular functional groups; quaternary ammonium fluoride salt with potential antibacterial fluoride-releasing activity, hydroxyl and amide group with hydrogen bonding potential to dentin collagen. Hydroxyl group also increases monomer hydrophilicity for better penetration into water-saturated dentin and sufficient resin-dentin bond. The synthesized HMTAF and its polymer showed no hydrolytic degradation in acidic environment, while MDPB and its polymer were partially decomposed under this challenge. The conversion of monomer HMTAF to polymer was illustrated by FT-IR. The results indicated that HMTAF is highly resistant to hydrolysis, polymerizable and non-cytotoxic to Vero cell lines. It is a potential monomer to be incorporated into resin adhesives for improving hydrolytic and enzymatic resistance. [ABSTRACT FROM AUTHOR]

Oral biofilm accumulation at the tooth–restoration interface often leads to recurrent dental caries and restoration failure. The objectives of this study were to: (1) develop a novel bioactive crown cement containing dimethylaminohexadecyl methacrylate (DMAHDM) and nano-sized amorphous calcium phosphate (NACP), and (2) investigate the mechanical properties, anti-biofilm activity, and calcium (Ca2+) and phosphate (PO43−) ion release of the crown cement for the first time. The cement matrix consisted of pyromellitic glycerol dimethacrylate and ethoxylated bisphenol-A dimethacrylate monomers and was denoted PEHB resin matrix. The following cements were tested: (1) RelyX luting cement (commercial control); (2) 55% PEHB + 45% glass fillers (experimental control); (3) 55% PEHB + 20% glass + 25% NACP + 0% DMAHDM; (4) 52% PEHB + 20% glass + 25% NACP + 3% DMAHDM; (5) 51% PEHB + 20% glass + 25% NACP + 4% DMAHDM; (6) 50% PEHB + 20% glass + 25% NACP + 5% DMAHDM. Mechanical properties and ion release were measured. Streptococcusmutans (S. mutans) biofilms were grown on cements, and colony-forming units (CFUs) and other biofilm properties were measured. The novel bioactive cement demonstrated strong antibacterial properties and high levels of Ca2+ and PO43− ion release to remineralize tooth lesions. Adding NACP and DMAHDM into the cement did not adversely affect the mechanical properties and dentin bonding strength. In conclusion, the novel NACP + DMAHDM crown cement has excellent potential for restoration cementation to inhibit caries by suppressing oral biofilm growth and increasing remineralization via Ca2+ and PO43− ions. The NACP + DMAHDM composition may have wide applicability to other biomaterials to promote hard-tissue formation and combat bacterial infection.

Context: Despite the advances in orthodontic material and treatment mechanics, the placement of fixed appliances increases the risk of enamel demineralization. The development of fluoride release adhesives has attracted considerable interests because the combined use of antimicrobials and fluoride enhances the cariostatic effect. Aim: To compare the shear bond strength (SBS) of fluoride release adhesives with established orthodontic adhesives and assess failure mode using adhesive remnant index (ARI). Settings and Design: The present study included 80 maxillary premolars which were randomly divided into four groups (n = 20) and were further subdivided into two subgroups A - Pumice prophylaxis (PP) and subgroup B - No PP (n = 10). Materials and Methods: Stainless steel brackets were bonded with Transbond XT, Transbond plus (TP) color change adhesive, Light Bond, and Clearfil protect bond. After debonding, the ARI was used to assess the mode of bracket failure. Statistical Analysis: The data were analyzed using two-way analysis of variance, Post-hoc Tukey Honest significant differences test, and Chi-square test. Results: The mean SBS of Group 4 was comparably higher regardless of PP. Brackets bonded with TP showed a comparable SBS to conventional Transbond XT. The ARI scores were predominately 2. Conclusions: Fluoride releasing adhesives combined with antibacterial monomer can play a vital role in reducing white spot lesions by enhancing the cariostatic effect especially in noncompliant\medically compromised patients.

Background: Considering the possibility of remaining bacteria in the cavity or invading via microgaps, the use of antibacterial agents in adhesive restoration may be beneficial. This study evaluated the effect of chlorhexidine on immediate and long-term shear bond strength of adhesives with and without antibacterial agent to dentin. Materials and Methods: In this in vitro study, the occlusal surfaces of 80 intact human premolars were removed to expose the flat midcoronal dentin. The teeth were assigned to four groups. Two adhesive systems, Clearfil SE Bond (SE) and Clearfil Protect Bond (PB) were used according to manufacturer′s instructions as the control groups. In the experimental groups, 2% chlorhexidine was applied prior to acidic primer of two adhesives. Then, resin composite was applied. Half of the specimens in each group were submitted to shear bond test after 24 h without thermocycling, and the other half were submitted to water storage for 6 months and thermocycling before testing. The data was analyzed using three-way analysis of variance (ANOVA) and t-test (α = 0.05). Results: Chlorhexidine application significantly decreased the initial bond strength (BS) of the two self-etch adhesives to dentin (P < 0.05). There was a significant reduction in BS of SE and PB after aging compared to initial bonding (P < 0.05). However, there was no significant difference between BS of the control and chlorhexidine-treated groups for the tested adhesives after aging. PB showed a lower BS than SE in two time periods (P < 0.05). Conclusion: Chlorhexidine was capable of diminishing the loss of BS of these adhesives over time. However, considering the negative effect of chlorhexidine on the initial BS, the benefits of chlorhexidine associated with these adhesives cannot possibly be used.

Objectives Eugenol has been used in dentistry due to its ability to inhibit the growth of a range of microorganisms, including facultative anaerobes commonly isolated from infected root canals. The aim of this study was to evaluate the antibacterial activity of the experimental composites containing eugenyl methacrylate monomer (EgMA), a polymeric derivative of eugenol, against a range of oral bacteria, commonly associated with failure of coronal and endodontic restorations. In vitro composite behavior and wettability were also studied in conjunction with their antibacterial activity. Methods EgMA monomer (5 and 10% by weight) was added into BisGMA/TEGDMA resin based formulations with filler mixtures of hydroxyapatite (HA) and zirconium oxide ZrO 2 . The antibacterial activity of the experimental composites against Enterococcus faecalis , Streptococcus mutans and Propionibacterium acnes were evaluated by direct contact test and compared with composite formulation without inclusion of EgMA. To clarify the antibacterial mode of action, agar diffusion test (ADT) was also performed. Water sorption, solubility, diffusion coefficient, contact angle and surface free energy as complementary clinically relevant properties were determined. Results Water sorption and wettability studies showed reduction of water uptake and surface free energy values with increasing content of EgMA monomer, resulting in significant increase in the hydrophobicity of the composites. No inhibition zones were detected in any of the composites tested against the three bacteria employed as expected, due to the absence of any leachable antibacterial agent. The covalently anchored EgMA monomer with the composite surface exhibited an effective bacteriostatic activity by reducing the number of CFUs of the three species of bacteria tested with no significant dependence on the concentration of EgMA at 5 and 10% by weight. The surface antibacterial activity R of the experimental composites were different against the three tested species with values in the range 2.7–6.1 following the order E . faecalis < S. mutans < P. acnes . Significance The incorporation of EgMA monomer within polymerizable formulations provides a novel approach to yield intrinsically antibacterial resin composites for different dental applications. [ABSTRACT FROM AUTHOR]

Objectives This study systematically review the literature to assess the effectiveness of antibacterial monomers incorporated into dental adhesive systems against major oral bacteria; as well as the research advances and the future prospects of this technology. Methods The following seven databases were screened: MedLine (PubMed), Lilacs, Ibecs, Web of Science, Scopus, Scielo , and The Cochrane Library . Furthermore, the online system Questel Orbit (Paris, France) was accessed to obtain patent data. The inclusion criteria were articles and patents that investigated the antimicrobial activity of antibacterial monomers in dental adhesive systems. Only documents written in English, Spanish or Portuguese were included. Results After screening, 33 studies and eight patents fulfiled all the criteria and were included. Antibacterial agents, such as QA, MDPB, DMAHM and DMADDM were found in patents, which claimed their incorporation into adhesive compositions, dental cements, composite resins. MDPB was the only antimicrobial monomer incorporated into a commercially available adhesive system, Clearfil Protect Bond™ (Kuraray Co. Ltd., Japan). All studies reported the inclusion of antimicrobial monomers in adhesive systems to be an effective dental treatment strategy. Significance There are potential areas to be explored with antibacterial monomers for dentistry, and their use could have important implications for future more conservative dental treatments. Although there is evidence of antibacterial activity from in vitro studies, clinical studies must be conducted to confirm the effectiveness of these materials in the prevention of dental pathologies. [ABSTRACT FROM AUTHOR]

Context: Despite the advances in orthodontic material and treatment mechanics, the placement of fixed appliances increases the risk of enamel demineralization. The development of fluoride release adhesives has attracted considerable interests because the combined use of antimicrobials and fluoride enhances the cariostatic effect.Aim: To compare the shear bond strength (SBS) of fluoride release adhesives with established orthodontic adhesives and assess failure mode using adhesive remnant index (ARI).Settings and Design: The present study included 80 maxillary premolars which were randomly divided into four groups (n = 20) and were further subdivided into two subgroups A - Pumice prophylaxis (PP) and subgroup B - No PP (n = 10).Materials and Methods: Stainless steel brackets were bonded with Transbond XT, Transbond plus (TP) color change adhesive, Light Bond, and Clearfil protect bond. After debonding, the ARI was used to assess the mode of bracket failure.Statistical Analysis: The data were analyzed using two-way analysis of variance, Post-hoc Tukey Honest significant differences test, and Chi-square test.Results: The mean SBS of Group 4 was comparably higher regardless of PP. Brackets bonded with TP showed a comparable SBS to conventional Transbond XT. The ARI scores were predominately 2.Conclusions: Fluoride releasing adhesives combined with antibacterial monomer can play a vital role in reducing white spot lesions by enhancing the cariostatic effect especially in noncompliant\medically compromised patients. [ABSTRACT FROM AUTHOR]

Background: Considering the possibility of remaining bacteria in the cavity or invading via microgaps, the use of antibacterial agents in adhesive restoration may be beneficial. This study evaluated the effect of chlorhexidine on immediate and long-term shear bond strength of adhesives with and without antibacterial agent to dentin. Materials and Methods: In this in vitro study, the occlusal surfaces of 80 intact human premolars were removed to expose the flat midcoronal dentin. The teeth were assigned to four groups. Two adhesive systems, Clearfil SE Bond (SE) and Clearfil Protect Bond (PB) were used according to manufacturer's instructions as the control groups. In the experimental groups, 2% chlorhexidine was applied prior to acidic primer of two adhesives. Then, resin composite was applied. Half of the specimens in each group were submitted to shear bond test after 24 h without thermocycling, and the other half were submitted to water storage for 6 months and thermocycling before testing. The data was analyzed using three-way analysis of variance (ANOVA) and t-test (a = 0.05). Results: Chlorhexidine application significantly decreased the initial bond strength (BS) of the two self-etch adhesives to dentin (P < 0.05). There was a significant reduction in BS of SE and PB after aging compared to initial bonding (P < 0.05). However, there was no significant difference between BS of the control and chlorhexidine-treated groups for the tested adhesives after aging. PB showed a lower BS than SE in two time periods (P < 0.05). Conclusion: Chlorhexidine was capable of diminishing the loss of BS of these adhesives over time. However, considering the negative effect of chlorhexidine on the initial BS, the benefits of chlorhexidine associated with these adhesives cannot possibly be used. [ABSTRACT FROM AUTHOR]

Pretreatment of dentin using colloidal platinum nanoparticles (CPtN) can enhance the bond strength of dentin adhesives. However, the combination of CPtN, which is negatively charged, with cationic monomer-containing adhesive may reduce the antibacterial activity of the original material. Thus, the purpose of this study was to assess the effect of CPtN on the bactericidal activity of two cationic antibacterial monomers, 12-methacryloyloxydodecylpyridinium bromide (MDPB) and methacryloxylethyl cetyl dimethyl ammonium chloride (DMAE-CB). The rapid killing effects of the two monomers against planktonic or attached Streptococcus mutans in the presence or absence of CPtN were examined by viable cell counts. The measurement of minimum inhibitory and bactericidal concentrations demonstrated that CPtN up to 2.5 mM has no antibacterial activity. In the absence of CPtN, rapid killing of both planktonic and attached Streptococcus mutans were achieved by the two cationic monomers. Combination with 0.1 mM CPtN did not reduce the bactericidal effects of the two monomers, indicating that CPtN may be used as a pretreatment with antibacterial adhesives. [ABSTRACT FROM AUTHOR]

The cytotoxicity of four self-etching primer/adhesive systems (Clearfil® SE Bond, Clearfil® Protect Bond, Mac Bond® II and FL® Bond) was tested against L929 fibroblasts. The primer or adhesive component of each adhesive system was diluted serially with the culture medium at a ratio of 1:1,000 and 1:4,000 (v/v). Cytotoxicity was identified by adding L929 cells in 24-well culture plates at an initial density of 35,000 cells mL-1. The cells were maintained for 5 days; every 24h, the medium was changed with fresh medium containing specific dilutions of the primer or adhesive components of the test materials. Cytotoxicity was assessed quantitatively at 24, 48, 72, 96 and 120h. Physiological and pathological cellular changes as well as reactions and growth of the cell cultures were examined under an inverted microscope. All self- etching systems were found to be cytotoxic to varying degrees; more pronounced toxic effects were observed at lower dilution (1:1,000 [v/v]). The adhesive components of Mac Bond® II and FL® Bond showed the highest cytotoxicity at 1:1,000 (v/v). The primer and adhesive of Clearifi® SE Bond, the primer of Mac Bond® II and the antibacterial monomer (MDPB)-containing Clearfil® Protect Bond (at 1:4,000 [v/v]) were relatively less cytotoxic. [ABSTRACT FROM AUTHOR]

This study examined the antibacterial activity of prepolymerized resin filler, in which the bactericide quaternary ammonium was immobilized. The experimental filler was prepared by grinding prepolymerized resin blocks of methacrylate monomers, silica particles, and the antibacterial monomer methacryloyloxydodecylpyridinium bromide (MDPB). The number of Streptococcus mutans after incubation for 18 h in contact with the experimental filler with or without protein adsorption by saliva treatment was determined, and adherence of bacteria to the filler surface was evaluated by scanning electron microscopy. Elution of unpolymerized MDPB from the filler and its influence on bacterial growth were also investigated. The growth of S. mutans was completely inhibited by contact with the experimental filler without saliva treatment. Although the effects were attenuated, the saliva-treated filler still exhibited growth inhibition at >99.9%. Less bacteria attached to the experimental filler than the control filler without MDPB, indicating that the reduction in bacterial number after contact with the experimental filler was not due to bacterial adherence to the particles. Unpolymerized MDPB at 1 μg/ml was eluted from the filler particles but was confirmed to have little effect on bacterial growth. The results indicate that the bactericide-immobilized filler containing MDPB shows significant bacteriostatic effects without releasing antibacterial components, and is useful for incorporation into various resin-based restoratives. [Copyright &y& Elsevier]

Oral biofilm accumulation at the tooth–restoration interface often leads to recurrent dental caries and restoration failure. The objectives of this study were to: (1) develop a novel bioactive crown cement containing dimethylaminohexadecyl methacrylate (DMAHDM) and nano-sized amorphous calcium phosphate (NACP), and (2) investigate the mechanical properties, anti-biofilm activity, and calcium (Ca2+) and phosphate (PO43−) ion release of the crown cement for the first time. The cement matrix consisted of pyromellitic glycerol dimethacrylate and ethoxylated bisphenol-A dimethacrylate monomers and was denoted PEHB resin matrix. The following cements were tested: (1) RelyX luting cement (commercial control); (2) 55% PEHB + 45% glass fillers (experimental control); (3) 55% PEHB + 20% glass + 25% NACP + 0% DMAHDM; (4) 52% PEHB + 20% glass + 25% NACP + 3% DMAHDM; (5) 51% PEHB + 20% glass + 25% NACP + 4% DMAHDM; (6) 50% PEHB + 20% glass + 25% NACP + 5% DMAHDM. Mechanical properties and ion release were measured. Streptococcusmutans (S. mutans) biofilms were grown on cements, and colony-forming units (CFUs) and other biofilm properties were measured. The novel bioactive cement demonstrated strong antibacterial properties and high levels of Ca2+ and PO43− ion release to remineralize tooth lesions. Adding NACP and DMAHDM into the cement did not adversely affect the mechanical properties and dentin bonding strength. In conclusion, the novel NACP + DMAHDM crown cement has excellent potential for restoration cementation to inhibit caries by suppressing oral biofilm growth and increasing remineralization via Ca2+ and PO43− ions. The NACP + DMAHDM composition may have wide applicability to other biomaterials to promote hard-tissue formation and combat bacterial infection. [ABSTRACT FROM AUTHOR]

Objectives: The dentin bonding often fails over time, leading to secondary caries and restoration failure. The objectives of this study were to develop an adhesive with dimethylaminohexadecyl methacrylate (DMAHDM) and nanoparticles of amorphous calcium phosphate (NACP), and investigate the effects of storage in artificial saliva for six months on the bonding durability, antibacterial activity, ion release and biofilm pH properties for the first time., Methods: DMAHDM was added at 5% (by mass) to Scotchbond Primer and Adhesive (SBMP). NACP was added at 10%, 20%, and 30% to SBMP adhesive. Dentin bonding durability, antibacterial activity against Streptococcus mutans biofilms, and calcium (Ca) and phosphate (P) ion liberation properties were investigated after 1 day and 6months of storage in artificial saliva., Results: Dentin bond strength (n = 50) had 25% loss after 6 months of aging for SBMP control. However, SBMP + DMAHDM+10NACP and SBMP + DMAHDM+20NACP showed no loss in bond strength after storage in artificial saliva for 6 months. The DMAHDM + NACP incorporation method dramatically reduced the biofilm metabolic activity and acid production, and decreased the biofilm CFU by four orders of magnitude, compared to SBMP control, even after 6 months of aging (p < 0.05). DMAHDM + NACP had long-lasting Ca and P ion releases, and raised the biofilm pH to 6.8, while the control group had a cariogenic biofilm pH of 4.5., Conclusions: Incorporating DMAHDM + NACP in bonding agent yielded potent and long-lasting antibacterial activity and ions liberation ability, and much higher long-term dentin bond strength after 6-month of aging. The new bonding agent is promising to inhibit caries at the restoration margins and increase the resin-dentin bonding longevity., Clinical Significance: The novel bioactive adhesive is promising to protect tooth structures from biofilm acids and secondary caries. NACP and DMAHDM have great potential for applications to a wide range of dental materials to reduce plaque and achieve therapeutic effects., (Copyright © 2019 Elsevier Ltd. All rights reserved.)