Search

Fluoride (F)-releasing restoratives typically are either weak mechanically or release only low levels of F ions. The objectives of this study were to: (1) develop a novel photo-cured nanocomposite with strong mechanical properties and high levels of sustained F ion release via a two-step "co-precipitation + spray-drying" technique to synthesize CaF 2 nanoparticles (nCaF 2); and (2) investigate the effect of spray-drying treatment after co-precipitation of nCaF 2 on mechanical properties and F ion release of composite. Two types of CaF 2 particles were synthesized: A co-precipitation method yielded CaF 2 cp; "co-precipitation + spray-drying" yielded nCaF 2 cpsd. Composites were fabricated with fillers of: (1) 0% CaF 2 + 70% glass; (2) 10% CaF 2 cp + 60% glass; (3) 15% CaF 2 cp + 55% glass; (4) 20% CaF 2 cp + 50% glass; (5) 10% nCaF 2 cpsd + 60% glass; (6) 15% nCaF 2 cpsd + 55% glass; and (7) 20% nCaF 2 cpsd + 50% glass. A commercial F-releasing nanocomposite served as control. The nCaF 2 cpsd had much smaller particle size (median = 32 nm) and narrower distribution (22–57 nm) than CaF 2 cp (median = 5.25 μm, 162 nm–67 μm). The composite containing nCaF 2 cpsd had greater flowability, flexural strength, elastic modulus and hardness than CaF 2 cp composite and commercial control composite. At 84-day immersion in water, the nanocomposites containing 20% nCaF 2 cpsd had 65 times higher cumulative F release, and 77 times greater long-term F-release rate, than commercial control. A novel two-step "co-precipitation + spray-drying" technique of synthesizing nCaF 2 was developed. The photo-cured nanocomposite containing 20% nCaF 2 cpsd possessed strong mechanical properties and excellent long-term F-release ability, and hence is promising for dental restoration applications to inhibit secondary caries. [ABSTRACT FROM AUTHOR]

Abstract Objective There has been no report on the effect of incorporating protein repellent 2-methacryloyloxyethyl phosphorylcholine (MPC) into a composite containing nanoparticles of amorphous calcium phosphate (NACP) on calcium (Ca) and phosphate (P) ion rechargeability. The objectives of this study were to develop a Ca and P ion-rechargeable and protein-repellent composite for the first time, and investigate the effects of MPC and NACP on mechanical properties, protein-repellency, anti-biofilm effects, and Ca and P ion recharge and re-release. Methods NACP were synthesized using a spray-drying technique. The resin contained ethoxylated bisphenol A dimethacrylate (EBPADMA) and pyromellitic glycerol dimethacrylate (PMGDM). Three NACP composites were made with 0 (control), 1.5%, and 3% of MPC. NACP (20%) and glass particles (50%) were also added into the resin. Protein adsorption was measured using a micro-bicinchoninic acid (BCA) method. A human saliva microcosm biofilm model was used to determine biofilm metabolic activity, lactic acid, and colony-forming units (CFU). Ca and P ion recharge and re-release were measured using a spectrophotometric method. Results Flexural strengths and moduli of CaP-rechargeable composites matched those of a commercial composite without CaP rechargeability (p > 0.1). Adding 1.5% and 3% MPC reduced protein adsorption to 1/3 and 1/5, respectively, that of commercial composite (p < 0.05). Adding 3% MPC suppressed biofilm metabolic activity and lactic acid production, and reduced biofilm CFU by nearly 2 logs. All three NACP composites had excellent ion rechargeability and higher levels of ion re-releases. One recharge yielded continuous ion release for 21 days. The release was maintained at the same level with increasing number of recharge cycles, indicating long-term ion release. Incorporation of MPC did not compromise the CaP ion rechargeability. Significance Incorporating 3% MPC into NACP nanocomposite greatly reduced protein adsorption, biofilm growth and lactic acid, decreasing biofilm CFU by nearly 2 logs, without compromising Ca and P recharge. This protein-repellent NACP-MPC rechargeable composite with long-term remineralization is promising for tooth restorations to inhibit secondary caries. [ABSTRACT FROM AUTHOR]

Objective Secondary caries is a primary reason for dental restoration failures. The objective of this study was to investigate the remineralization of human dentin lesions in vitro via restorations using nanocomposites containing nanoparticles of amorphous calcium phosphate (NACP) or NACP and tetracalcium phosphate (TTCP) for the first time. Methods NACP was synthesized by a spray-drying technique and incorporated into a resin consisting of ethoxylated bisphenol A dimethacrylate (EBPADMA) and pyromellitic glycerol dimethacrylate (PMGDM). After restoring the dentin lesions with nanocomposites as well as a non-releasing commercial composite control, the specimens were treated with cyclic demineralization (pH 4, 1 h per day) and remineralization (pH 7, 23 h per day) for 4 or 8 weeks. Calcium (Ca) and phosphate (P) ion releases from composites were measured. Dentin lesion remineralization was measured at 4 and 8 weeks by transverse microradiography (TMR). Results Lowering the pH increased ion release of NACP and NACP-TTCP composites. At 56 days, the released Ca concentration in mmol/L (mean ± SD; n = 3) was (13.39 ± 0.72) at pH 4, much higher than (1.19 ± 0.06) at pH 7 (p < 0.05). At 56 days, P ion concentration was (5.59 ± 0.28) at pH 4, much higher than (0.26 ± 0.01) at pH 7 (p < 0.05). Quantitative microradiography showed typical subsurface dentin lesions prior to the cyclic demineralization/remineralization treatment, and dentin remineralization via NACP and NACP-TTCP composites after 4 and 8 weeks of treatment. At 8 weeks, NACP nanocomposite achieved dentin lesion remineralization (mean ± SD; n = 15) of (48.2 ± 11.0)%, much higher than (5.0 ± 7.2)% for dentin in commercial composite group after the same cyclic demineralization/remineralization regimen (p < 0.05). Significance Novel NACP-based nanocomposites were demonstrated to achieve dentin lesion remineralization for the first time. These results, coupled with acid-neutralization and good mechanical properties shown previously, indicate that the NACP-based nanocomposites are promising for restorations to inhibit caries and protect tooth structures. [ABSTRACT FROM AUTHOR]

The objectives of this study were to develop a novel method to remineralize dentin lesions, and investigate the remineralization effects of poly (amido amine) (PAMAM) dendrimer plus a bonding agent with nanoparticles of amorphous calcium phosphate (NACP) in a cyclic artificial saliva/lactic acid environment for the first time. Dentin lesions were produced via phosphoric acid. Four groups were tested: (1) dentin control, (2) dentin with PAMAM, (3) dentin with NACP bonding agent, and (4) dentin with PAMAM plus NACP bonding agent. Specimens were treated with cyclic artificial saliva/lactic acid. The remineralized dentin was examined using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), hardness and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). NACP bonding agent yielded a dentin shear bond strength similar to commercial controls (Prime & Bond NT, Dentsply; Scotchbond Multi-purpose, 3M) ( p > 0.1). Increasing NACP in bonding agent from 0 to 40% did not affect bond strength. NACP bonding agent neutralized the acid and released Ca ions with concentrations of 4 to 20 mmol/L, and P ions of 2 to 9 mmol/L. PAMAM or NACP bonding agent alone achieved slight remineralization. The PAMAM + NACP group achieved the greatest dentin remineralization p < 0.05). At 20 days, PAMAM + NACP increased the hardness of pre-demineralized dentin to reach the normal dentin hardness ( p > 0.1). In conclusion, superior remineralization of PAMAM + NACP bonding agent was demonstrated for the first time. PAMAM + NACP bonding agent induced dentin remineralization under acid challenge, when conventional remineralization methods such as PAMAM alone did not work well. The novel PAMAM + NACP bonding agent method is promising to improve the longevity of resin-dentin bonds, inhibit caries, and protect teeth. [ABSTRACT FROM AUTHOR]

Objectives The objective of this study was to investigate the effects of poly (amido amine) (PAMAM), composite with nanoparticles of amorphous calcium phosphate (NACP), and the combined PAMAM + NACP nanocomposite treatment, on remineralization of demineralized dentin in a cyclic artificial saliva/lactic acid environment for the first time. Methods Dentin specimens were prepared and demineralized with 37% phosphoric acid for 15 s. Four groups were prepared: (1) dentin control, (2) dentin coated with PAMAM, (3) dentin with NACP composite, (4) dentin with PAMAM + NACP. Specimens were treated with a cyclic artificial saliva/lactic acid regimen for 21 days. Acid neutralization and calcium (Ca) and phosphate (P) ion concentrations were measured. The remineralized dentin specimens were examined by scanning electron microscopy (SEM) and hardness testing. Results NACP nanocomposite had mechanical properties similar to commercial control composites (p > 0.1). NACP composite had acid-neutralization and Ca and P ion release capability. PAMAM or NACP composite each alone achieved remineralization and increased the hardness of demineralized dentin (p < 0.05). PAMAM + NACP nanocomposite achieved the greatest mineral regeneration in demineralized dentin and the greatest hardness increase in demineralized dentin, which approached the hardness of healthy dentin (p > 0.1). Significance The superior remineralization efficacy of PAMAM + NACP was demonstrated for the first time. PAMAM + NACP induced remineralization in demineralized dentin in an acid challenge environment, when conventional remineralization methods such as PAMAM did not work well. The novel PAMAM + NACP composite approach is promising for a wide range of dental applications to inhibit caries and protect tooth structures. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this study were to develop a self-healing dental composite containing poly(urea-formaldehyde) (PUF) shells with triethylene glycol dimethacrylate (TEGDMA) and N,N-dihydroxyethyl-p-toluidine (DHEPT) as healing liquid, and to investigate the mechanical properties of the composite and its self-healing efficacy after water-aging for 6 months.Methods: PUF microspheres were synthesized encapsulating a TEGDMA-DHEPT healing liquid. Composite containing 30% of a resin matrix and 70% of glass fillers by mass was incorporated with 0%, 2.5%, 5%, 7.5% and 10% of microcapsules. A flexural test was used to measure flexural strength and elastic modulus. A single edge V-notched beam method was used to measure fracture toughness (KIC) and self-healing efficacy. Specimens were water-aged at 37 °C for 1 day to 6 months and then tested for self-healing. Fractured specimens were healed while being immersed in water to examine self-healing efficacy, in comparison with that in air.Results: Incorporation of up to 7.5% of microcapsules into the resin composite achieved effective self-healing, without adverse effects on the virgin mechanical properties of the composite (p>0.1). An excellent self-healing efficacy of 64-77% recovery was obtained (mean±sd; n=6). Six months of water-aging did not decrease the self-healing efficacy compared to 1 day (p>0.1). Exposure to water did not decrease the healing efficacy, compared to that healed in air (p>0.1).Conclusions: A composite was developed with excellent self-healing efficacy even while being immersed in water. The self-healing efficacy did not decrease with increasing water-aging time for 6 months.Clinical Significance: The novel self-healing composite may be promising for dental applications to heal cracks, resist fracture, and increase the durability and longevity. [ABSTRACT FROM AUTHOR]

Objectives Calcium phosphate (CaP) composites with Ca and P ion release can remineralize tooth lesions and inhibit caries. But the ion release lasts only a few months. The objectives of this study were to develop rechargeable CaP dental composite for the first time, and investigate the Ca and P recharge and re-release of composites with nanoparticles of amorphous calcium phosphate (NACP) to achieve long-term inhibition of caries. Methods Three NACP nanocomposites were fabricated with resin matrix of: (1) bisphenol A glycidyl dimethacrylate (BisGMA) and triethylene glycol dimethacrylate (TEGDMA) at 1:1 mass ratio (referred to as BT group); (2) pyromellitic glycerol dimethacrylate (PMGDM) and ethoxylated bisphenol A dimethacrylate (EBPADMA) at 1:1 ratio (PE group); (3) BisGMA, TEGDMA, and Bis[2-(methacryloyloxy)ethyl] phosphate (BisMEP) at 2:1:1 ratio (BTM group). Each resin was filled with 20% NACP and 50% glass particles, and the composite was photo-cured. Specimens were tested for flexural strength and elastic modulus, Ca and P ion release, and Ca and P ion recharge and re-release. Results NACP nanocomposites had strengths 3-fold of, and elastic moduli similar to, commercial resin-modified glass ionomer controls. CaP ion recharge capability was the greatest for PE group, followed by BTM group, with BT group being the lowest ( p < 0.05). For each recharge cycle, CaP re-release reached similarly high levels, showing that CaP re-release did not decrease with more recharge cycles. After six recharge/re-release cycles, NACP nanocomposites without further recharge had continuous CaP ion release for 42 d. Significance Novel rechargeable CaP composites achieved long-term and sustained Ca and P ion release. Rechargeable NACP nanocomposite is promising for caries-inhibiting restorations, and the Ca and P ion recharge and re-release method has wide applicability to dental composites, adhesives, cements and sealants to achieve long-term caries-inhibition. [ABSTRACT FROM AUTHOR]

Objective Bulk fracture is one of the primary reasons for resin-based dental restoration failures. To date, there has been no report on the use of polymerizable dental monomers with acceptable biocompatibility to develop a resin with substantial self-healing capability. The objectives of this study were to: (1) develop a self-healing resin containing microcapsules with triethylene glycol dimethacrylate (TEGDMA)- N , N -dihydroxyethyl- p -toluidine (DHEPT) healing liquid in poly(urea-formaldehyde) (PUF) shells for the first time, and (2) determine the physical and mechanical properties, self-healing efficiency, and fibroblast cytotoxicity. Methods Microcapsules of polymerizable TEGDMA-DHEPT in PUF were prepared via an in situ polymerization method. Microcapsules were added into a BisGMA-TEGDMA resin at microcapsule mass fractions of 0%, 5%, 10%, 15% and 20%. A flexural test was used to measure composite strength and elastic modulus. A single edge V-notched beam method was used to measure fracture toughness K IC and self-healing efficiency. Results Flexural strength and elastic modulus (mean ± sd; n = 6) of resin containing 5–15% microcapsules were similar to control without microcapsules ( p > 0.1). Adding microcapsules into the resin increased the virgin K IC , which was about 40% higher at 15% microcapsules than that with 0% microcapsules ( p < 0.05). Specimens were fractured and healed, then fractured again to measure the healed K IC . A self-healing efficiency of about 65% in K IC recovery was obtained with 10–20% microcapsules. All specimens with 0–20% microcapsules had fibroblast viability similar to control without resin eluents ( p > 0.1). Significance Self-healing dental resin containing microcapsules with polymerizable TEGDMA-DHEPT healing liquid in PUF shells were prepared for the first time with excellent self-healing capability. These microcapsules and self-healing resins containing them may be promising for dental restorations to heal cracks/damage and increase durability. [ABSTRACT FROM AUTHOR]

Objectives: The tooth-resin bond is the weak link of restoration, with secondary caries as a main reason for failure. Calcium phosphate-containing resins are promising for remineralization; however, calcium (Ca) and phosphate (P) ion releases last only a couple of months. The objectives of this study were to develop the first rechargeable CaP bonding agent and investigate the key factors that determine CaP ion recharge and re-release.Methods: Nanoparticles of amorphous calcium phosphate (NACP) were synthesized. Pyromellitic glycerol dimethacrylate (PMGDM), ethoxylated bisphenol-A dimethacrylate (EBPADMA), 2-hydroxyethyl methacrylate (HEMA), and bisphenol-A glycidyl dimethacrylate (BisGMA) were used to synthesize three adhesives (denoted PE, PEH and PEHB). NACP were mixed into adhesive at 0-30% by mass. Dentin shear bond strengths were measured. Adhesive specimens were tested for Ca and P initial ion release. Then the ion-exhausted specimens were immersed in Ca and P solution to recharge the specimens, and the recharged specimens were then used to measure ion re-release for 7 days as one cycle. Then these specimens were again recharged and the re-release was measured for 7 days as the second cycle. Three recharge/re-release cycles were tested.Results: PEHB had the highest dentin bond strength (p<0.05). Increasing NACP content from 0 to 30% did not affect dentin bond strength (p>0.1), but increased CaP release and re-release (p<0.05). PEHB-NACP had the greatest recharge/re-release, and PE-NACP had the least (p<0.05). Ion release remained high and did not decrease with increasing the number of recharge/re-release cycles (p>0.1). After the third cycle, specimens without further recharge had continuous CaP ion release for 2-3 weeks.Significance: Rechargeable CaP bonding agents were developed for the first time to provide long-term Ca and P ions to promote remineralization and reduce caries. Incorporation of NACP into adhesive had no negative effect on dentin bond strength. Increasing NACP filler level increased the ion recharge and re-release capability. The new CaP recharge method and PMGDM-EBPADMA-NACP composition may have wide application in adhesives, composites and cements, to combat caries and remineralize lesions. [ABSTRACT FROM AUTHOR]

Objectives Secondary caries at the tooth-restoration margins remains a main reason for restoration failure. The objectives of this study were to: (1) combine protein-repellent 2-methacryloyloxyethyl phosphorylcholine (MPC) with quaternary ammonium dimethylaminohexadecyl methacrylate (DMAHDM) to develop a new dental adhesive with double benefits of protein-repellent and antibacterial capabilities for the first time; and (2) investigate the effects on protein adsorption, anti-biofilm activity, and dentin bond strength. Methods MPC and DMAHDM were incorporated into Scotchbond Multi-Purpose (SBMP) primer and adhesive. Dentin shear bond strengths were measured using extracted human molars. Protein adsorption onto the adhesive resin surfaces was determined by the micro bicinchoninic acid (BCA) method. A dental plaque microcosm biofilm model with human saliva as inoculum was used to investigate biofilm metabolic activity, colony-forming unit (CFU) counts, lactic acid production and live/dead staining of biofilms on resins. Results Incorporation of 7.5% MPC and 5% DMAHDM into primer and adhesive did not adversely affect the dentin shear bond strength ( p > 0.1). The resin with 7.5% MPC + 5% DMAHDM had protein adsorption that was nearly 20-fold less than SBMP control ( p < 0.05). The resin with 7.5% MPC + 5% DMAHDM had much stronger antibacterial effects than using MPC or DMAHDM alone ( p < 0.05). Biofilm CFU counts on the resin with 7.5% MPC + 5% DMAHDM were reduced by more than 4 orders of magnitude, compared to SBMP control. Significance The use of double agents (protein-repellent MPC + antibacterial DMAHDM) in dental adhesive achieved much stronger inhibition of biofilms than using each agent alone. The novel protein-repellent and antibacterial bonding agent is promising to reduce biofilm/plaque buildup and reduce recurrent caries at the tooth-restoration margins. [ABSTRACT FROM AUTHOR]

Objectives: Fracture and secondary caries are the primary reasons for dental restoration failure. The objective of this study was to develop a self-healing composite to heal cracks, while containing dimethylaminohexadecyl methacrylate (DMAHDM) for antibacterial function and nanoparticles of amorphous calcium phosphate (NACP) for remineralization. Methods: Microcapsules were synthesized with poly(urea-formaldehyde) (PUF) shells containing triethylene glycol dimethacrylate (TEGDMA) and N,N-dihydroxyethyl-p-toluidine (DHEPT) as healing liquid. Composite contained 20 mass% of NACP and 35% glass fillers. In addition, composite contained 0%, 2.5%, 5%, 7.5%, or 10% of microcapsules. A single edge Vnotched beam method measured fracture toughness (KIC) and self-healing efficiency. A dental plaque microcosm biofilm model was used to test the antibacterial properties. Results: Incorporation of microcapsules up to 7.5% into the composite did not adversely affect the mechanical properties (p > 0.1). Successful self-healing was achieved, with KIC recovery of 65-81% (mean ± sd; n = 6) to regain the load-bearing capability after composite fracture. The self-healing DMAHDM-NACP composite displayed a strong antibacterial potency, inhibiting biofilm viability and lactic acid production, and reducing colony-forming units by 3-4 orders of magnitude, compared to control composite without DMAHDM. Conclusions: A dental composite was developed with triple benefits of self-healing after fracture, antibacterial activity, and remineralization capability for the first time. Clinical significance: The self-healing, antibacterial and remineralizing composite may be promising for tooth cavity restorations to combat bulk fracture and secondary caries. The method of using triple agents (self-healing microcapsules, DMAHDM, and NACP) may have wide applicability to other dental composites, adhesives, sealants and cements. [ABSTRACT FROM AUTHOR]

Objective Recurrent caries at the margins is a primary reason for restoration failure. The objectives of this study were to develop bonding agent with the double benefits of antibacterial and remineralizing capabilities, to investigate the effects of NACP filler level and solution pH on Ca and P ion release from adhesive, and to examine the antibacterial and dentin bond properties. Methods Nanoparticles of amorphous calcium phosphate (NACP) and a quaternary ammonium monomer (dimethylaminododecyl methacrylate, DMADDM) were synthesized. Scotchbond Multi-Purpose (SBMP) primer and adhesive served as control. DMADDM was incorporated into primer and adhesive at 5% by mass. NACP was incorporated into adhesive at filler mass fractions of 10%, 20%, 30% and 40%. A dental plaque microcosm biofilm model was used to test the antibacterial bonding agents. Calcium (Ca) and phosphate (P) ion releases from the cured adhesive samples were measured vs. filler level and solution pH of 7, 5.5 and 4. Results Adding 5% DMADDM and 10-40% NACP into bonding agent, and water-aging for 28 days, did not affect dentin bond strength, compared to SBMP control at 1 day (p>0.1). Adding DMADDM into bonding agent substantially decreased the biofilm metabolic activity and lactic acid production. Total microorganisms, total streptococci, and mutans streptococci were greatly reduced for bonding agents containing DMADDM. Increasing NACP filler level from 10% to 40% in adhesive increased the Ca and P ion release by an order of magnitude. Decreasing solution pH from 7 to 4 increased the ion release from adhesive by 6-10 folds. Significance Bonding agents containing antibacterial DMADDM and remineralizer NACP were formulated to have Ca and P ion release, which increased with NACP filler level from 10% to 40% in adhesive. NACP adhesive was "smart" and dramatically increased the ion release at cariogenic pH 4, when these ions would be most-needed to inhibit caries. Therefore, bonding agent containing DMADDM and NACP may be promising to inhibit biofilms and remineralize tooth lesions thereby increasing the restoration longevity. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Quaternary amine charge density is important because when the negatively charged bacteria contact the positive quaternary amine charge, the electric balance is disturbed and the bacterium could be disrupted. There has been no report on the effects of charge density on the antibacterial efficacy of dental bonding agents. The objective of this study was to synthesize a new quaternary ammonium methacrylate, and investigate the effects of charge density of bonding agent on bacteria early-attachment, biofilm colony-forming units (CFU) and dentin bond strength. Methods: Dimethylaminododecyl methacrylate (DMAHDM) with an alkyl chain length of 16 was synthesized and mixed into Scotchbond Multi-Purpose adhesive and primer (SBMP) at mass fractions of 0%, 2.5%, 5%, 7.5%, and 10%. A microtensile dentin bond test was performed. The density of quaternary ammonium groups was measured using a fluorescein dye method. Streptococcus mutans (S. mutans) early-attachment was examined at 4h, and biofilm colony-forming units (CFU) were measured at 2 days. Results: All groups had similar microtensile bonding strengths (mean±sd; n =40) of about 60MPa (p >0.1). Quaternary amine charge density of bonding agents monotonically increased with increasing DMAHDM mass fraction. Bacteria early-attachment coverage greatly decreased with increasing DMAHDM content in the resin. Biofilm CFU at 10% DMAHDM was reduced by more than 4log, compared to SBMP control. Charge density of bonding agent was inversely proportional to bacteria early-attachment coverage and biofilm CFU. Significance: Increasing the quaternary amine charge density of dentin bonding agent resin was shown to greatly reduce S. mutans attachment and decrease biofilm CFU by four orders of magnitude, without compromising the dentin bond strength. The new DMAHDM is promising for use in bonding agents and other antibacterial restorative materials to inhibit caries. [Copyright &y& Elsevier]

Abstract: Objectives: Antibacterial primer and adhesive are promising to inhibit biofilms and caries. Since restorations in vivo are exposed to saliva, one concern is the attenuation of antibacterial activity due to salivary pellicles. The objective of this study was to investigate the effects of salivary pellicles on bonding agents containing a new monomer dimethylaminododecyl methacrylate (DMADDM) or nanoparticles of silver (NAg) against biofilms for the first time. Methods: DMADDM and NAg were synthesized and incorporated into Scotchbond Multi-Purpose adhesive and primer. Specimens were either coated or not coated with salivary pellicles. A microcosm biofilm model was used with mixed saliva from ten donors. Two types of culture medium were used: an artificial saliva medium (McBain), and Brain Heart Infusion (BHI) medium without salivary proteins. Metabolic activity, colony-forming units (CFU), and lactic acid production of plaque microcosm biofilms were measured (n =6). Results: Bonding agents containing DMADDM and NAg greatly inhibited biofilm activities, even with salivary pellicles. When using BHI, the pre-coating of salivary pellicles on resin surfaces significantly decreased the antibacterial effect (p <0.05). When using artificial saliva medium, pre-coating of salivary pellicles on resin did not decrease the antibacterial effect. These results suggest that artificial saliva yielded medium-derived pellicles on resin surfaces, which provided attenuating effects on biofilms similar to salivary pellicles. Compared with the commercial control, the DMADDM-containing bonding agent reduced biofilm CFU by about two orders of magnitude. Significance: Novel DMADDM- and NAg-containing bonding agents substantially reduced biofilm growth even with salivary pellicle coating on surfaces, indicating a promising usage in saliva-rich environment. DMADDM and NAg may be useful in a wide range of primers, adhesives and other restoratives to achieve antibacterial and anti-caries capabilities. [Copyright &y& Elsevier]

Objectives: The objectives of this study were to investigate: (1) the antibacterial activity of two antibacterial monomers, dimethylaminododecyl methacrylate (DMADDM) and dimethylammoniumethyl dimethacrylate (DMAEDM), against eight different species of oral pathogens for the first time; (2) the cytotoxicity of DMAEDM and DMADDM. Methods: DMAEDM and DMADDM were synthesized by reacting a tertiary amine group with an organo-halide. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against eight species of bacteria were tested. Time-kill determinations were performed to examine the bactericidal kinetics. Cytotoxicity of monomers on human gingival fibroblasts (HGF) was assessed using a methyl thiazolyltetrazolium assay and live/ dead viability assay. Results: DMADDM showed strong bactericidal activity against all bacteria, with MIC of 1.2- 9.8 μ0g/mL. DMAEDM had MIC of 20-80 μg/mL. Time-kill determinations indicated that DMADDM and DMAEDM had rapid killing effects against eight species of bacteria, and eliminated all bacteria in 30 min at the concentration of 4-fold MBC. Median lethal concentration for DMADDM and DMAEDM was between 20 and 40 μg/mL, which was 20-fold higher than 1-2 μg/mL for BisGMA control. Conclusions: DMAEDM and DMADDM were tested in time-kill assay against eight species of oral bacteria for the first time. Both were effective in bacteria-inhibition, but DMADDM had a higher potency than DMAEDM. Different killing efficacy was found against different bacteria species. DMAEDM and DMADDM had much lower cytotoxicity than BisGMA. Therefore, DMADDM and DMAEDM are promising for use in bonding agents and other restorative/ preventive materials to combat a variety of oral pathogens [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Composites are the principal material for tooth cavity restorations due to their esthetics and direct-filling capabilities. However, composites accumulate biofilms in vivo, and secondary caries due to biofilm acids is the main cause of restoration failure. The objectives of this study were to: (1) synthesize new antibacterial monomers and (2) develop nanocomposite containing nanoparticles of amorphous calcium phosphate (NACP) and antibacterial monomer. Methods: Two new antibacterial monomers were synthesized: dimethylaminohexane methacrylate (DMAHM) with a carbon chain length of 6, and dimethylaminododecyl methacrylate (DMADDM) with a chain length of 12. A spray-drying technique was used to make NACP. DMADDM was incorporated into NACP nanocomposite at mass fractions of 0%, 0.75%, 1.5%, 2.25% and 3%. A flexural test was used to measure composite strength and elastic modulus. A dental plaque microcosm biofilm model with human saliva as inoculum was used to measure viability, metabolic activity, and lactic acid production of biofilms on composites. Results: The new DMAHM was more potent than a previous quaternary ammonium dimethacrylate (QADM). DMADDM was much more strongly antibacterial than DMAHM. The new DMADDM–NACP nanocomposite had strength similar to that of composite control (p >0.1). At 3% DMADDM in the composite, the metabolic activity of adherent biofilms was reduced to 5% of that on composite control. Lactic acid production by biofilms on composite containing 3% DMADDM was reduced to only 1% of that on composite control. Biofilm colony-forming unit (CFU) counts on composite with 3% DMADDM were reduced by 2–3 orders of magnitude. Significance: New antibacterial monomers were synthesized, and the carbon chain length had a strong effect on antibacterial efficacy. The new DMADDM–NACP nanocomposite possessed potent anti-biofilm activity without compromising load-bearing properties, and is promising for antibacterial and remineralizing dental restorations to inhibit secondary caries. [Copyright &y& Elsevier]

Abstract: Objective: Antibacterial primer and adhesive are promising to help combat biofilms and recurrent caries. The objectives of this study were to compare novel bonding agent containing quaternary ammonium dimethacrylate (QADM) with bonding agent containing nanoparticles of silver (NAg) in antibacterial activity, contact-inhibition vs. long-distance inhibition, glucosyltransferases (gtf) gene expressions, and cytotoxicity for the first time. Methods: QADM and NAg were incorporated into Scotchbond Multi-Purpose adhesive and primer. Microtensile dentin bond strength was measured. Streptococcus mutans (S. mutans) biofilm on resin surface (contact-inhibition) as well as S. mutans in culture medium away from the resin surface (long-distance inhibition) were tested for metabolic activity, colony-forming units (CFUs), lactic acid production, and gtf gene expressions. Eluents from cured primer/adhesive samples were used to examine cytotoxicity against human gingival fibroblasts. Results: Bonding agent with QADM greatly reduced CFU and lactic acid of biofilms on the resin surface (p <0.05), while having no effect on S. mutans in culture medium away from the resin surface. In contrast, bonding agent with NAg inhibited not only S. mutans on the resin surface, but also S. mutans in culture medium away from the resin surface. Bonding agent with QADM suppressed gtfB, gtfC and gtfD gene expressions of S. mutans on its surface, but not away from its surface. Bonding agent with NAg suppressed S. mutans gene expressions both on its surface and away from its surface. Bonding agents with QADM and NAg did not adversely affect microtensile bond strength or fibroblast cytotoxicity, compared to control (p >0.1). Significance: QADM-containing adhesive had contact-inhibition and inhibited bacteria on its surface, but not away from its surface. NAg-containing adhesive had long-distance killing capability and inhibited bacteria on its surface and away from its surface. The novel antibacterial adhesives are promising for caries-inhibition restorations, and QADM and NAg could be complimentary agents in inhibiting bacteria on resin surface as well as away from resin surface. [Copyright &y& Elsevier]

Objectives: The main reason for restoration failure is secondary caries caused by biofilm acids. Replacing the failed restorations accounts for 50-70% of all operative work. The objectives of this study were to incorporate a new quaternary ammonium monomer (dimethylaminododecyl methacrylate, DMADDM) and nanoparticles of silver (NAg) into a primer and an adhesive, and to investigate their effects on antibacterial and dentin bonding properties. Methods: Scotchbond Multi-Purpose (SBMP) served as control. DMADDM was synthesized and incorporated with NAg into primer/adhesive. A dental plaque microcosm biofilm model with human saliva was used to investigate metabolic activity, colony-forming units (CFU), and lactic acid. Dentin shear bond strengths were measured. Results: Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the new DMADDM were orders of magnitude lower than those of a previous quaternary ammonium dimethacrylate (QADM). Uncured primer with DMADDM had much larger inhibition zones than QADM (p < 0.05). Cured primer/adhesive with DMADDM-NAg greatly reduced biofilm metabolic activity (p < 0.05). Combining DMADDM with NAg in primer/adhesive resulted in less CFU than DMADDM alone (p < 0.05). Lactic acid production by biofilms was reduced by 20- fold via DMADDM-NAg, compared to control. Incorporation of DMADDM and NAg into primer/adhesive did not adversely affect dentin bond strength. Conclusions: A new antibacterial monomer DMADDM was synthesized and incorporated into primer/adhesive for the first time. The bonding agents are promising to combat residual bacteria in tooth cavity and invading bacteria at tooth-restoration margins to inhibit caries. DMADDM and NAg are promising for use into a wide range of dental adhesive systems and restoratives. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Secondary caries at the restoration margins remains the main reason for failure. Although calcium phosphate (CaP) composites are promising for caries inhibition, there has been no report of CaP composite to inhibit caries in situ. The objectives of this study were to investigate the caries-inhibition effect of nanocomposite containing nanoparticles of amorphous calcium phosphate (NACP) in a human in situ model for the first time, and to determine colony-forming units (CFU) and Ca and P ion concentrations of biofilms on the composite restorations. Methods: NACP with a mean particle size of 116nm were synthesized via a spray-drying technique. Two composites were fabricated: NACP nanocomposite, and control composite filled with glass particles. Twenty-five volunteers wore palatal devices containing bovine enamel slabs with cavities restored with NACP or control composite. After 14 days, the adherent biofilms were collected for analyses. Transverse microradiography determined the enamel mineral profiles at the margins, and the enamel mineral loss ΔZ was measured. Results: NACP nanocomposite released Ca and P ions and the release significantly increased at cariogenic low pH (p <0.05). Biofilms on NACP nanocomposite contained higher Ca (p =0.007) and P ions (p =0.005) than those of control (n =25). There was no significant difference in biofilm CFU between the two composites (p >0.1). Microradiographs showed typical subsurface lesions in enamel next to control composite, but much less lesion around NACP nanocomposite. Enamel mineral loss ΔZ (mean±sd; n =25) around NACP nanocomposite was 13.8±9.3μm, much less than 33.5±19.0μm of the control (p =0.001). Significance: Novel NACP nanocomposite substantially reduced caries formation in a human in situ model for the first time. Enamel mineral loss at the margins around NACP nanocomposite was less than half of the mineral loss around control composite. Therefore, the Ca and P ion-releasing NACP nanocomposite is promising for caries-inhibiting restorations. [Copyright &y& Elsevier]

Abstract: Objectives: Fluoride (F) releasing dental restoratives are promising to promote remineralization and combat caries. The objectives of this study were to develop nanocomposite containing calcium fluoride nanoparticles (nCaF2), and to investigate the long-term mechanical durability including wear, thermal-cycling and long-term water-aging behavior. Methods: Two types of fillers were used: nCaF2 with a diameter of 53nm, and glass particles of 1.4μm. Four composites were fabricated with fillers of: (1) 0% nCaF2 +65% glass; (2) 10% nCaF2 +55% glass; (3) 20% nCaF2 +45% glass; (4) 30% nCaF2 +35% glass. Three commercial materials were also tested. Specimens were subjected to thermal-cycling between 5°C and 60°C for 105 cycles, three-body wear for 4×105 cycles, and water-aging for 2 years. Results: After thermal-cycling, the nCaF2 nanocomposites had flexural strengths in the range of 100–150MPa, five times higher than the 20–30MPa for resin-modified glass ionomer (RMGI). The wear scar depth showed an increasing trend with increasing nCaF2 filler level. Wear of nCaF2 nanocomposites was within the range of wear for commercial controls. Water-aging decreased the strength of all materials. At 2 years, flexural strength was 94MPa for nanocomposite with 10% nCaF2, 60MPa with 20% nCaF2, and 48MPa with 30% nCaF2. They are 3–6 fold higher than the 15MPa for RMGI (p <0.05). SEM revealed air bubbles and cracks in a RMGI, while composite control and nCaF2 nanocomposites appeared dense and solid. Significance: Combining nCaF2 with glass particles yielded nanocomposites with long-term mechanical properties that were comparable to those of a commercial composite with little F release, and much better than those of RMGI controls. These strong long-term properties, together with their F release being comparable to RMGI as previously reported, indicate that the nCaF2 nanocomposites are promising for load-bearing and caries-inhibiting restorations. [Copyright &y& Elsevier]

Abstract: Objectives: Previous studies have developed calcium phosphate and fluoride releasing composites. Other studies have incorporated chlorhexidine (CHX) particles into dental composites. However, CHX has not been incorporated in calcium phosphate and fluoride composites. The objectives of this study were to develop nanocomposites containing amorphous calcium phosphate (ACP) or calcium fluoride (CaF2) nanoparticles and CHX particles, and investigate Streptococcus mutans biofilm formation and lactic acid production for the first time. Methods: Chlorhexidine was frozen via liquid nitrogen and ground to obtain a particle size of 0.62μm. Four nanocomposites were fabricated with fillers of: nano ACP; nano ACP+10% CHX; nano CaF2; nano CaF2 +10% CHX. Three commercial materials were tested as controls: a resin-modified glass ionomer, and two composites. S. mutans live/dead assay, colony-forming unit (CFU) counts, biofilm metabolic activity, and lactic acid were measured. Results: Adding CHX fillers to ACP and CaF2 nanocomposites greatly increased their antimicrobial capability. ACP and CaF2 nanocomposites with CHX that were inoculated with S. mutans had a growth medium pH>6.5 after 3 d, while the control commercial composites had a cariogenic pH of 4.2. Nanocomposites with CHX reduced the biofilm metabolic activity by 10–20 folds and reduced the acid production, compared to the controls. CFU on nanocomposites with CHX were three orders of magnitude less than that on commercial composite. Mechanical properties of nanocomposites with CHX matched a commercial composite without fluoride. Significance: The novel calcium phosphate and fluoride nanocomposites could be rendered antibacterial with CHX to greatly reduce biofilm formation, acid production, CFU and metabolic activity. The antimicrobial and remineralizing nanocomposites with good mechanical properties may be promising for a wide range of tooth restorations with anti-caries capabilities. [Copyright &y& Elsevier]

Abstract: Objectives: Calcium and phosphate ion-releasing resin composites are promising for remineralization. However, there has been no report on incorporating antibacterial agents to these composites. The objective of this study was to develop antibacterial and mechanically strong nanocomposites incorporating a quaternary ammonium dimethacrylate (QADM), nanoparticles of silver (NAg), and nanoparticles of amorphous calcium phosphate (NACP). Methods: The QADM, bis(2-methacryloyloxyethyl) dimethylammonium bromide (ionic dimethacrylate-1), was synthesized from 2-(N,N-dimethylamino)ethyl methacrylate and 2-bromoethyl methacrylate. NAg was synthesized by dissolving Ag 2-ethylhexanoate salt in 2-(tert-butylamino)ethyl methacrylate. Mechanical properties were measured in three-point flexure with bars of 2mm×2mm×25mm (n =6). Composite disks (diameter=9mm, thickness=2mm) were inoculated with Streptococcus mutans. The metabolic activity and lactic acid production of biofilms were measured (n =6). Two commercial composites were used as controls. Results: Flexural strength and elastic modulus of NACP+QADM, NACP+NAg, and NACP+QADM+NAg matched those of commercial composites with no antibacterial property (p >0.1). The NACP+QADM+NAg composite decreased the titer counts of adherent S. mutans biofilms by an order of magnitude, compared to the commercial composites (p <0.05). The metabolic activity and lactic acid production of biofilms on NACP+QADM+NAg composite were much less than those on commercial composites (p <0.05). Combining QADM and NAg rendered the nanocomposite more strongly antibacterial than either agent alone (p <0.05). Significance: QADM and NAg were incorporated into calcium phosphate composite for the first time. NACP+QADM+NAg was strongly antibacterial and greatly reduced the titer counts, metabolic activity, and acid production of S. mutans biofilms, while possessing mechanical properties similar to commercial composites. These nanocomposites are promising to have the double benefits of remineralization and antibacterial capabilities to inhibit dental caries. [Copyright &y& Elsevier]

Abstract: The need for bone repair has increased as the population ages. Stem cell-scaffold approaches hold immense promise for bone tissue engineering. However, currently, preformed scaffolds for cell delivery have drawbacks including the difficulty to seed cells deep into the scaffold, and inability for injection in minimally-invasive surgeries. Current injectable polymeric carriers and hydrogels are too weak for load-bearing orthopedic applications. The objective of this study was to develop an injectable and mechanically-strong stem cell construct for bone tissue engineering. Calcium phosphate cement (CPC) paste was combined with hydrogel microbeads encapsulating human umbilical cord mesenchymal stem cells (hUCMSCs). The hUCMSC-encapsulating composite paste was fully injectable under small injection forces. Cell viability after injection matched that in hydrogel without CPC and without injection. Mechanical properties of the construct matched the reported values of cancellous bone, and were much higher than previous injectable polymeric and hydrogel carriers. hUCMSCs in the injectable constructs osteodifferentiated, yielding high alkaline phosphatase, osteocalcin, collagen type I, and osterix gene expressions at 7 d, which were 50–70 fold higher than those at 1 d. Mineralization by the hUCMSCs at 14 d was 100-fold that at 1 d. In conclusion, a fully injectable, mechanically-strong, stem cell–CPC scaffold construct was developed. The encapsulated hUCMSCs remained viable, osteodifferentiated, and synthesized bone minerals. The new injectable stem cell construct with load-bearing capability may enhance bone regeneration in minimally-invasive and other orthopedic surgeries. [Copyright &y& Elsevier]

Abstract: Human bone marrow mesenchymal stem cells (hBMSCs) require an invasive procedure to harvest, and have lower self-renewal potential with aging. Umbilical cord mesenchymal stem cells (hUCMSCs) are a relatively new stem cell source; this study reveals a self-setting and load-bearing calcium phosphate construct that encapsulates these stem cells. The flexural strength (mean±sd; n =5) of the hUCMSC-encapsulating calcium phosphate cement (CPC) increased from (3.5±1.1) MPa without polyglactin fibers, to (11.7±2.1) MPa with 20% of polyglactin fibers (p <0.05). hUCMSCs attached to the bone mineral-mimicking scaffold in the osteogenic media and differentiated down the osteogenic lineage, yielding elevated alkaline phosphatase (ALP) and osteocalcin (OC) gene expressions. ALP and OC on the CPC-fiber scaffold was 2-fold those on CPC control without fibers. hUCMSCs encapsulated inside the scaffolds retained excellent viability and cell density. The encapsulated hUCMSCs inside four different constructs successfully differentiated down the osteogenic lineage and synthesized bone minerals, as confirmed by mineral staining, SEM, and XRD. The percentage of mineral area synthesized by the encapsulated hUCMSCs increased from about 3% at day-7, to 12% at day-21 (p <0.05). In conclusion, this study demonstrated that hUCMSCs encapsulated in the bioengineered scaffolds osteo-differentiated and synthesized bone minerals. The self-setting CPC–chitosan–fiber scaffold supported the viability and osteogenic differentiation of the encapsulated hUCMSCs, and had mechanical strength matching that of cancellous bone. [Copyright &y& Elsevier]

Abstract: Objectives: Secondary caries and restoration fracture are the two main challenges facing tooth cavity restorations. The objective of this study was to develop a composite using tetracalcium phosphate (TTCP) fillers and whiskers to be stress-bearing, and to be “smart” to increase the calcium (Ca) and phosphate (PO4) ion release at cariogenic pH. Methods: TTCP was ball-milled to obtain four different particle sizes: 16.2, 2.4, 1.3, and 0.97μm. Whiskers fused with nano-sized silica were combined with TTCP as fillers in a resin. Filler level mass fractions varied from 0 to 75%. Ca and PO4 ion releases were measured vs. time at pH of 7.4, 6, and 4. Composite mechanical properties were measured via three-point flexure before and after immersion in solutions at the three pH. Results: TTCP composite without whiskers had flexural strength similar to a resin-modified glass ionomer (Vitremer) and previous Ca–PO4 composites. With whiskers, the TTCP composite had a flexural strength (mean±S.D.; n =5) of (116±9)MPa, similar to (112±14)MPa of a stress-bearing, non-releasing hybrid composite (TPH) (p >0.1). The Ca release was (1.22±0.16)mmol/L at pH of 4, higher than (0.54±0.09) at pH of 6, and (0.22±0.06) at pH of 7.4 (p <0.05). PO4 release was also dramatically increased at acidic pH. After immersion, the TTCP–whisker composite matched the strength of TPH at all three pH (p >0.1); both TTCP–whisker composite and TPH had strengths about threefold that of a releasing control. Significance: The new TTCP–whisker composite was “smart” and increased the Ca and PO4 release dramatically when the pH was reduced from neutral to a cariogenic pH of 4, when these ions are most needed to inhibit caries. Its strength was two- to threefold higher than previously known Ca–PO4 composites and resin-modified glass ionomer. This composite may have the potential to provide the necessary combination of load-bearing and caries-inhibiting capabilities. [Copyright &y& Elsevier]

Abstract: Objectives: Seven million people suffer bone fractures each year in the U.S., and musculoskeletal conditions cost $215billion/year. The objectives of this study were to develop moldable/injectable, mechanically strong and in situ-hardening calcium phosphate cement (CPC) composite scaffolds for bone regeneration and delivery of osteogenic cells and growth factors. Methods: Tetracalcium phosphate [TTCP: Ca4(PO4)2O] and dicalcium phosphate (DCPA: CaHPO4) were used to fabricate self-setting calcium phosphate cement. Strong and macroporous scaffolds were developed via absorbable fibers, biopolymer chitosan, and mannitol porogen. Following established protocols, MC3T3-E1 osteoblast-like cells (Riken, Hirosaka, Japan) were cultured on the specimens and inside the CPC composite paste carrier. Results: The scaffold strength was more than doubled via reinforcement (p <0.05). Relationships and predictive models were established between matrix properties, fibers, porosity, and overall composite properties. The cement injectability was increased from about 60% to nearly 100%. Cell attachment and proliferation on the new composite matched those of biocompatible controls. Cells were able to infiltrate into the macropores and anchor to the bone mineral-like nano-apatite crystals. For cell delivery, alginate hydrogel beads protected cells during cement mixing and setting, yielding cell viability measured via the Wst-1 assay that matched the control without CPC (p >0.1). For growth factor delivery, CPC powder:liquid ratio and chitosan content provided the means to tailor the rate of protein release from CPC carrier. Significance: New CPC scaffolds were developed that were strong, tough, macroporous and osteoconductive. They showed promise for injection in minimally invasive surgeries, and in delivering osteogenic cells and osteoinductive growth factors to promote bone regeneration. Potential applications include various dental, craniofacial, and orthopedic reconstructions. [Copyright &y& Elsevier]

Abstract: Objectives: Nanoparticles of dicalcium phosphate anhydrous (DCPA) were synthesized in our laboratory for the first time and incorporated into a dental resin. Our goal was to develop a mechanically strong dental composite that has Ca and PO4 ion release to combat tooth caries, and to investigate the effects of whisker reinforcement, DCPA particle size and silanization. Methods: DCPA nanoparticles and two larger DCPA particles were used with nano-silica-fused whiskers as fillers in a resin matrix. Composite mechanical properties were measured via three-point flexure, and the release of Ca and PO4 ions were measured versus time. Results: Using DCPA nanoparticles with a diameter of 112nm, the composite at a DCPA:whisker mass ratio of 1:1 had a flexural strength (mean±S.D.; n =5) of (112±17)MPa, not significantly different from (112±14)MPa of a commercial non-releasing composite; both were higher than (29±7)MPa for the composite at DCPA:whisker of 1:0 (p <0.05). The composite with DCPA particle size of 112nm released Ca to a concentration of 0.85mmol/L and PO4 of 3.48mmol/L, higher than Ca of 0.67mmol/L and PO4 of 1.11mmol/L using DCPA with 12μm particle size (p <0.05). Silanization of DCPA increased the composite strength at DCPA:whisker of 1:0 compared to that without silanization, but decreased the Ca and PO4 release (p <0.05). Increasing the DCPA particle surface area increased the Ca and PO4 release. Significance: Decreasing the DCPA particle size increased the Ca and PO4 release; whisker reinforcement increased the composite strength by two- to three-fold. The nano DCPA–whisker composites, with high strength and Ca and PO4 release, may provide the needed, unique combination of stress-bearing and caries-inhibiting capabilities. [Copyright &y& Elsevier]

Abstract: Calcium phosphate cement (CPC) can be molded and self-hardens in vivo to form resorbable hydroxyapatite with excellent osteoconductivity. The objective of this study was to develop an injectable, macroporous and strong CPC, and to investigate the effects of porogen and absorbable fibers. Water-soluble mannitol was used as porogen and mixed with CPC at mass fractions from 0% to 50%. CPC with 0–40% mannitol was fully extruded under a syringe force of 10 n. The paste with 50% mannitol required a 100-N force which extruded only 66% of the paste. At fiber volume fraction of 0–5%, the paste was completely extruded. However, at 6% and 7.5% fibers, some fibers were left in the syringe after the paste was extruded. The injectable CPC scaffold had a flexural strength (mean±sd; ) of (3.2±1.0) MPa, which approached the reported strengths for sintered porous hydroxyapatite implants and cancellous bone. In summary, the injectability of a ceramic scaffold, a macroporous CPC, was studies for the first time. Processing parameters were tailored to achieve high injectability, macroporosity, and strength. The injectable and strong CPC scaffold may be useful in surgical sites that are not freely accessible by open surgery or when using minimally invasive techniques. [Copyright &y& Elsevier]

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. 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). 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). 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. • The DMAHDM-loaded Ti effectively inhibit biofilms on the surface in the high-risk period of peri-implant inflammation. • The released DMAHDM inhibited the surrounding planktonic S. aureus and S. sanguinis. • After 4 weeks, the modified Ti was still able to show antibacterial effects on S. aureus and S. sanguinis biofilm. • The DMAHDM-loaded Ti is biocompatible, with no cytotoxicity to soft tissue seal and osseointegration related cells. [ABSTRACT FROM AUTHOR]

Dental caries is caused by acids from biofilms. pH-sensitive nanoparticle carriers could achieve improved targeted effectiveness. The objectives of this study were to develop novel mesoporous silica nanoparticles carrying nanosilver and chlorhexidine (nMS-nAg-Chx), and investigate the inhibition of biofilms as well as the modulation of biofilm to suppress acidogenic and promote benign species for the first time. nMS-nAg was synthesized via a modified sol-gel method. Carboxylate group functionalized nMS-nAg (COOH-nMS-nAg) was prepared and Chx was added via electrostatic interaction. Minimal inhibitory concentration (MIC), inhibition zone, and growth curves were evaluated. Streptococcus mutans (S. mutans), Streptococcus gordonii (S. gordonii), and Streptococcus sanguinis (S. sanguinis) formed multispecies biofilms. Metabolic activity, biofilm lactic acid, exopolysaccharides (EPS), and TaqMan real-time polymerase chain reaction (RT-PCR) were tested. Biofilm structures and biomass were observed by scanning electron microscopy (SEM) and live/dead bacteria staining. nMS-nAg-Chx possessed pH-responsive properties, where Chx release increased at lower pH. nMS-nAg-Chx showed good biocompatibility. nMS-nAg-Chx exhibited a strong antibacterial function, reducing biofilm metabolic activity and lactic acid as compared to control (p < 0.05, n = 6). Moreso, biofilm biomass was dramatically suppressed in nMS-nAg-Chx groups. In control group, there was an increasing trend of S. mutans proportion in the multispecies biofilm, with S. mutans reaching 89.1% at 72 h. In sharp contrast, in nMS-nAg-Chx group of 25 μg/mL, the ratio of S. mutans dropped to 43.7% and the proportion of S. gordonii and S. sanguinis increased from 19.8% and 10.9 to 69.8% and 56.3%, correspondingly. pH-sensitive nMS-nAg-Chx had potent antibacterial effects and modulated biofilm toward a non-cariogenic tendency, decreasing the cariogenic species nearly halved and increasing the benign species approximately twofold. nMS-nAg-Chx is promising for applications in mouth rinse and endodontic irrigants, and as fillers in resins to prevent caries. [Display omitted] [ABSTRACT FROM AUTHOR]

Pit and fissure sealants with antibacterial and remineralization properties have broad application prospects in caries prevention. The objectives of this study were to: (1) develop a novel pit and fissure sealant containing CaF 2 nanoparticles (nCaF 2) and dimethylaminohexadecyl methacrylate (DMAHDM); and (2) investigate the effects of nCaF 2 and DMAHDM on biofilm response and fluoride (F) ion release for the first time. Helioseal F was used as a control. Bioactive sealants were formulated with DMAHDM and nCaF 2. Flow properties, enamel shear bond strength, hardness and F ion releases were measured. Streptococcus mutans (S. mutans) biofilms were grown on sealants. Biofilm metabolic activity, lactic acid production, colony-forming units (CFU), and pH of biofilm culture medium were measured. Adding 5% DMAHDM and 20% nCaF 2 did not reduce the paste flow and enamel bond strength, compared to control (p < 0.05). Hardness of sealants with 20% nCaF 2 and DMAHDM was higher than control (p < 0.05). The F ion release from 20% nCaF 2 was much higher than that of commercial control (p < 0.05). The sealant with DMAHDM reduced the S. mutans biofilm CFU by 4 logs. The pH in biofilm medium of the new bioactive sealant was much higher (pH 6.8) than that of commercial sealant (pH 4.66) (p < 0.05). The new bioactive pit and fissure sealant with nCaF 2 and DMAHDM achieved high fluoride release and strong antibacterial performance. This novel fluoride-releasing and antibacterial sealant is promising to inhibit caries and promote the remineralizaton of enamel and dentin. [ABSTRACT FROM AUTHOR]

Dental plaque build-up on the cervical area adjacent to gingival margins is a trigger factor for secondary caries around restored root caries lesions. Dimethylaminohexadecyl methacrylate (DMAHDM) and amorphous calcium phosphate nanoparticles (NACP) impart anti-caries effect by reducing the bacterial growth and releasing high concentrations of calcium and phosphate ions, respectively. The present study explored the optimization and formulation of dental composite with increased concentration of DMAHDM combined with NACP and its effect on mechanical behavior and antibacterial response. DMAHDM was incorporated into dental composite formulation at 3% and 5% with 20% NACP fillers. Mechanical properties were assessed by flexural strength and elastic modulus. The cationic charge density of the samples was determined using fluorescein staining assay. A human saliva-derived microcosm biofilm model was used to assess antibacterial response via colony-forming units, metabolic activities, lactic acid production, and live/dead assay. Surface roughness was measured after 48 h-biofilm formation. The viability of human saliva microcosm biofilms was DMAHDM concentration-dependent, where all the microbiological assays were substantially reduced in the presence of 5%DMAHDM. The increased DMAHDM concentration mirrors an increased surface charge density of composites by 8–12 folds and reduced the growth of cariogenic species by 2–5 log (p ≤ 0.05). Metabolic activity and lactic acid were reduced by 70–90% and 48–99%, respectively. Increasing DMAHDM concentration up to 5% and its association with NACP fillers did not adversely affect the mechanical properties. A highly potent antibiofilm bioactive composite for root caries restorations having DMAHDM-NACP could be flexibly tailored during formulation without detrimental outcome for mechanical function. The enhanced antibacterial performance of the novel bioactive composite has great potential to suppress the dental plaque build-up that triggers secondary caries around the restored root caries lesions. [ABSTRACT FROM AUTHOR]

• S. mutans rnc gene-deletion reduced the biofilm growth and acid production in antibacterial monomer. • DMAHDM was shown to have a stronger antibacterial function than CHX. • The dual strategy of combining rnc -deletion with DMAHDM achieved the greatest reduction in biofilms. • The novel dual strategy is promising for a wide range of dental applications. Antibacterial quaternary ammonium monomers (QAMs) are used in resins. The rnc gene in Streptococcus mutans (S. mutans) plays a key role in resisting antibiotics. The objectives of this study were to investigate for the first time: (1) the effects of rnc deletion on S. mutans biofilms and acid production; (2) the combined effects of rnc deletion with dimethylaminohexadecyl methacrylate (DMAHDM) on biofilm-inhibition efficacy. Parent S. mutans strain UA159 (ATCC 700610) and the rnc -deleted S. mutans were used. Bacterial growth, minimum inhibitory concentration (MIC), and minimal bactericidal concentration (MBC) were measured to analyze the bacterial susceptibility of the parent and rnc -deleted S. mutans against DMAHDM, with the gold-standard chlorhexidine (CHX) as control. Biofilm biomass, polysaccharide and lactic acid production were measured. The drug-susceptibility of the rnc -deleted S. mutans to DMAHDM or CHX was 2-fold higher than parent S. mutans. The drug-susceptibility did not increase after 10 passages (p < 0.05). Deleting the rnc gene increased the biofilm susceptibility to DMAHDM or CHX by 2-fold. The rnc -deletion in S. mutans reduced biofilm biomass, polysaccharide and lactic acid production, even at no drugs. DMAHDM was nearly 40 % more potent than the gold-standard CHX. The combination of rnc deletion + DMAHDM treatment achieved the greatest reduction in biofilm biomass, polysaccharide synthesis, and lactic acid production. Gene modification by deleting the rnc in S. mutans reduced the biofilm growth and acid production, and the rnc deletion + DMAHDM method showed the greatest biofilm-inhibition efficacy, for the first time. The dual strategy of antibacterial monomer + bacterial gene modification shows great potential to control biofilms and inhibit caries. [ABSTRACT FROM AUTHOR]

Injectable and self-setting calcium phosphate cement scaffold (CPC) capable of encapsulating and delivering stem cells and bioactive agents would be highly beneficial for dental and craniofacial repairs. The objectives of this study were to: (1) develop a novel injectable CPC scaffold encapsulating human periodontal ligament stem cells (hPDLSCs) and metformin (Met) for bone engineering; (2) test bone regeneration efficacy in vitro and in vivo. hPDLSCs were encapsulated in degradable alginate fibers, which were then mixed into CPC paste. Five groups were tested: (1) CPC control; (2) CPC + hPDLSC-fibers + 0% Met (CPC + hPDLSCs + 0%Met); (3) CPC + hPDLSC-fibers + 0.1% Met (CPC + hPDLSCs + 0.1%Met); (4) CPC + hPDLSC-fibers + 0.2% Met (CPC + hPDLSCs + 0.2%Met); (5) CPC + hPDLSC-fibers + 0.4% Met (CPC + hPDLSCs + 0.4%Met). The injectability, mechanical properties, metformin release, and hPDLSC osteogenic differentiation and bone mineral were determined in vitro. A rat cranial defect model was used to evaluate new bone formation. The novel construct had good injectability and physical properties. Alginate fibers degraded in 7 days and released hPDLSCs, with 5-fold increase of proliferation (p＜0.05). The ALP activity and mineral synthesis of hPDLSCs were increased by Met delivery (p＜0.05). Among all groups, CPC+hPDLSCs+ 0.1%Met showed the greatest cell mineralization and osteogenesis, which were 1.5–10 folds those without Met (p＜0.05). Compared to CPC control, CPC+hPDLSCs+ 0.1%Met enhanced bone regeneration in rats by 9 folds, and increased vascularization by 3 folds (p＜0.05). The novel injectable construct with hPDLSC and Met encapsulation demonstrated excellent efficacy for bone regeneration and vascularization in vivo in an animal model. CPC+hPDLSCs+ 0.1%Met is highly promising for dental and craniofacial applications. • We developed a novel injectable and mechanically strong CPC-alginate hydrogel-hPDLSC scaffold with different dosages of metformin for bone tissue engineering. • The novel construct had much greater bone regeneration and vascularization potency than control in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Objectives: Calcium phosphate cement (CPC) is promising for dental and craniofacial applications due to its ability to be injected or filled into complex-shaped bone defects and molded for esthetics, and its resorbability and replacement by new bone. The objective of this study was to investigate bone regeneration via novel macroporous CPC containing absorbable fibers, hydrogel microbeads and growth factors in critical-sized cranial defects in rats. Methods: Mannitol porogen and alginate hydrogel microbeads were incorporated into CPC. Absorbable fibers were used to provide mechanical reinforcement to CPC scaffolds. Six CPC groups were tested in rats: (1) control CPC without macropores and microbeads; (2) macroporous CPC+large fiber; (3) macroporous CPC+large fiber+nanofiber; (4) same as (3), but with rhBMP2 in CPC matrix; (5) same as (3), but with rhBMP2 in CPC matrix+rhTGF-β1 in microbeads; (6) same as (3), but with rhBMP2 in CPC matrix+VEGF in microbeads. Rats were sacrificed at 4 and 24 weeks for histological and micro-CT analyses. Results: The macroporous CPC scaffolds containing porogen, absorbable fibers and hydrogel microbeads had mechanical properties similar to cancellous bone. At 4 weeks, the new bone area fraction (mean±sd; n =5) in CPC control group was the lowest at (14.8±3.3)%, and that of group 6 (rhBMP2+VEGF) was (31.0±13.8)% (p <0.05). At 24 weeks, group 4 (rhBMP2) had the most new bone of (38.8±15.6)%, higher than (12.7±5.3)% of CPC control (p <0.05). Micro-CT revealed nearly complete bridging of the critical-sized defects with new bone for several macroporous CPC groups, compared to much less new bone formation for CPC control. Significance: Macroporous CPC scaffolds containing porogen, fibers and microbeads with growth factors were investigated in rat cranial defects for the first time. Macroporous CPCs had new bone up to 2-fold that of traditional CPC control at 4 weeks, and 3-fold that of traditional CPC at 24 weeks, and hence may be useful for dental, craniofacial and orthopedic applications. [ABSTRACT FROM AUTHOR]

Objective Patients with dry mouth often have an acidic oral environment lacking saliva that provides calcium (Ca) and phosphate (P) ions. However, there has been no study on dentin remineralization by placing samples in an acidic solution without Ca and P ions. Previous studies used saliva-like solutions with neutral pH and Ca and P ions. Therefore, the objective of this study was to investigate a novel method of combining poly(amido amine) (PAMAM) with a composite of nanoparticles of amorphous calcium phosphate (NACP) on dentin remineralization in an acidic solution without Ca and P ions for the first time. Methods Demineralized dentin specimens were tested into four groups: (1) dentin control, (2) dentin coated with PAMAM, (3) dentin with NACP nanocomposite, (4) dentin with PAMAM plus NACP composite. Specimens were treated with lactic acid at pH 4 without initial Ca and P ions for 21 days. Acid neutralization and Ca and P ion concentrations were measured. Dentin specimens were examined by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and hardness testing vs. remineralization efficacy. Results NACP composite had mechanical properties similar to commercial control composites (p > 0.1). NACP composite neutralized acid and released Ca and P ions. PAMAM alone failed to induce dentin remineralization. NACP alone achieved mild remineralization and slightly increased dentin hardness at 21 days (p > 0.1). In contrast, the PAMAM + NACP nanocomposite method in acid solution without initial Ca and P ions greatly remineralized the pre-demineralized dentin, restoring its hardness to approach that of healthy dentin (p > 0.1). Significance Dentin remineralization via PAMAM + NACP in pH 4 acid without initial Ca and P ions was demonstrated for the first time, when conventional methods such as PAMAM did not work. The novel PAMAM + NACP nanocomposite method is promising to protect tooth structures, especially for patients with reduced saliva to inhibit caries. [ABSTRACT FROM AUTHOR]

A low-shrinkage-stress resin-based cement with antibacterial properties could be beneficial to create a cement with lower stress at the tooth-restoration interface, which could help to enhance the longevity of the fixed dental restoration by reducing microleakage and recurrent caries. To date, there has been no report on the development of a low-shrinkage-stress and bio-interactive cement. Therefore, the objectives of this study were to develop a novel low-shrinkage-stress resin-based cement containing dimethylaminohexadecyl methacrylate (DMAHDM) and investigate the mechanical and antibacterial properties for the first time. The monomers urethane dimethacrylate (UDMA) and triethylene glycol divinylbenzyl ether (TEG-DVBE) were combined and denoted as UV resin. Three cements were fabricated: (1) UV+ 0%DMAHDM (experimental control); (2) UV+ 3%DMAHDM, (3) UV+ %5DMAHDM. RelyX Ultimate cement was used as commercial control. Mechanical properties and Streptococcus mutans (S. mutans) biofilms growth on cement were evaluated. The novel bio-interactive cement demonstrated excellent antibacterial and mechanical properties. Compared to commercial and experimental controls, adding DMAHDM into the UV cement significantly reduced colony forming unit (CFU) counts by approximately 7 orders of magnitude, metabolic activities from 0.29 ± 0.03 A 540 /cm2 to 0.01 ± 0.01 A 540 /cm2, and lactic acid production from 22.3 ± 0.74 mmol/L to 1.2 ± 0.27 mmol/L (n = 6) (p < 0.05). The low-shrinkage-stress cement demonstrated a high degree of conversion of around 70 %, while reducing the shrinkage stress by approximately 60%, compared to a commercial control (p < 0.05). The new antibacterial low-shrinkage-stress resin-based cement provides strong antibacterial action and maintains excellent mechanical properties with reduced polymerization shrinkage stress. A low-shrinkage-stress resin-based cement containing DMAHDM was developed with potent antibacterial effects and promising mechanical properties. This cement may potentially enhance the longevity of fixed dental restoration such as a dental crown, inlay, onlay, and veneers through its excellent mechanical properties, low shrinkage stress, and strong antibacterial properties. [ABSTRACT FROM AUTHOR]

The cariogenic biofilm on enamel, restoration, and bonding interface is closely related to dental caries and composite restoration failure. Enamel remineralization at adhesive interface is conducive to protecting bonding interface and inhibiting secondary caries. This study intended to assess the remineralization efficiency of adhesive with dimethylaminohexadecyl methacrylate (DMAHDM) and nanoparticles of amorphous calcium phosphate (NACP) on initial caries lesion of biofilm-coated enamel. Artificial initial carious lesion was created via 72-hour immersion in demineralization solution and cariogenic biofilm was formed after 24-hour culture of Streptococcus mutans (S. mutans). Specimens were then divided into 4 groups: enamel control, enamel treated with NACP, DMAHDM and NACP+DMAHDM respectively. Samples next underwent 7-day cycling, 4 h in BHIS (brain heart infusion broth containing 1 % sucrose) and 20 h in AS (artificial saliva) per day. The pH of BHIS was tested daily. So did the concentration of calcium and phosphate in BHIS and AS. Live/dead staining, colony-forming unit (CFU) count, and lactic acid production of biofilms were measured 7 days later. The enamel remineralization efficiency was evaluated by microhardness testing and transverse microradiography (TMR) quantitatively. Enamel of NACP+DMAHDM group demonstrated excellent remineralization effectiveness. And the NACP+DMAHDM adhesive released a great number of Ca2+ and PO 4 3- ions, increased pH to 5.81 via acid neutralization, decreased production of lactic acid, and reduced CFU count of S. mutans (P < 0.05). The NACP+DMAHDM adhesive would be applicable to preventing secondary caries, strengthening enamel-adhesive interface, and extending the lifespan of composite restoration. [ABSTRACT FROM AUTHOR]

Objectives Calcium phosphate cements (CPCs) are promising for dental and craniofacial repairs. The objectives of this study were to: (1) develop an injectable cell delivery system based on encapsulation of induced pluripotent stem cell-derived mesenchymal stem cells (iPSMSCs) in microbeads; (2) develop a novel tissue engineered construct by dispersing iPSMSC-microbeads in CPC to investigate bone regeneration in an animal model for the first time. Methods iPSMSCs were pre-osteoinduced for 2 weeks (OS-iPSMSCs), or transduced with bone morphogenetic protein-2 (BMP2-iPSMSCs). Cells were encapsulated in fast-degradable alginate microbeads. Microbeads were mixed with CPC paste and filled into cranial defects in nude rats. Four groups were tested: (1) CPC-microbeads without cells (CPC control); (2) CPC-microbeads-iPSMSCs (CPC-iPSMSCs); (3) CPC-microbeads-OS-iPSMSCs (CPC-OS-iPSMSCs); (4) CPC-microbeads-BMP2-iPSMSCs (CPC-BMP2-iPSMSCs). Results Cells maintained good viability inside microbeads after injection. The microbeads were able to release the cells which had more than 10-fold increase in live cell density from 1 to 14 days. The cells exhibited up-regulation of osteogenic markers and deposition of minerals. In vivo , new bone area fraction (mean ± SD; n = 5) for CPC-iPSMSCs group was (22.5 ± 7.6)%. New bone area fractions were (38.9 ± 18.4)% and (44.7 ± 22.8)% for CPC-OS-iPSMSCs group and CPC-BMP2-iPSMSCs group, respectively, 2–3 times the (15.6 ± 11.2)% in CPC control at 12 weeks ( p < 0.05). Cell-CPC constructs accelerated scaffold resorption, with CPC-BMP2-iPSMSCs having remaining scaffold material that was 7-fold less than CPC control. Significance Novel injectable CPC-microbead-cell constructs promoted bone regeneration, with OS-iPSMSCs and BMP2-iPSMSCs having 2–3 fold the new bone of CPC control. Cell delivery accelerated scaffold resorption, with CPC-BMP2-iPSMSC having remaining scaffold material that was 7-fold less than CPC control. Therefore, CPC-microbead-iPSMSC is a promising injectable material for orthopedic, dental and craniofacial bone regenerations. [ABSTRACT FROM AUTHOR]

Objectives: White spot lesions are the most undesired side-effect of fixed orthodontic treatments. The objectives of this study were to combine nanoparticles of silver (NAg) with 2-methacryloyloxyethyl phosphorylcholine (MPC) to develop a modified resin-modified glass ionomer cement (RMGI) as orthodontic cement with double benefits of antibacterial and protein-repellent capabilities for the first time.Methods: NAg and MPC were incorporated into a commercial RMGI. Another commercial orthodontic adhesive also served as control. Enamel shear bond strengths (SBS) were determined. Protein adsorption was measured via a micro bicinchoninic acid method. A dental plaque microcosm biofilm model with human saliva as inoculum was tested. Biofilms adherent on the cement samples and planktonic bacteria in the culture medium away from the cement surfaces were both evaluated for bacterial metabolic activity, colony-forming units (CFU), and lactic acid production.Results: Adding 0.1% NAg and 3% MPC to RMGI, and water-aging for 30 days, did not adversely affect the SBS, compared to the unmodified RMGI control (p>0.1). The modified RMGI containing 0.1% NAg and 3% MPC achieved the greatest reduction in protein adsorption, bacterial adhesion, CFU, metabolic activity and lactic acid production. The RMGI containing 0.1% NAg and 3% MPC inhibited not only the bacteria on its surface, but also the bacteria away from the surface in the culture medium.Conclusions: The incorporation of double agents (antibacterial NAg+protein-repellent MPC) into RMGI achieved much stronger inhibition of biofilms than using each agent alone. The novel antibacterial and protein-repellent RMGI with substantially-reduced biofilm acids is promising as an orthodontic cement to combat white spot lesions in enamel. [ABSTRACT FROM AUTHOR]

Objectives: Biofilm acids contribute to secondary caries which is a reason for restoration failure. Previous studies synthesized nanoparticles of amorphous calcium phosphate (NACP) and dimethylaminohexadecyl methacrylate (DMAHDM). The objectives of this study were to develop DMAHMD-NACP nanocomposite for double benefits of antibacterial and remineralization capabilities, and investigate the DMAHMD mass fraction effects on fracture toughness and biofilm response of NACP nanocomposite for the first time.Methods: DMAHDM was incorporated into NACP nanocomposite at mass fractions of 0% (control), 0.75%, 1.5%, 2.25% and 3%. A single edge V-notched beam method was used to measure fracture toughness K(IC). A dental plaque microcosm biofilm model using human saliva as inoculum was used to measure the antibacterial properties of composites.Results: K(IC) was about 1 MPa×m(1/2) for all composite (mean±sd; n=6). Adding DMAHDM from 0% to 3% did not affect K(IC) (p>0.1). Lactic acid production by biofilms on composite containing 3% DMAHDM was reduced to less than 1% of that on composite control. Metabolic activity of adherent biofilms on composite containing 3% DMAHDM was reduced to 4% of that on composite control. Biofilm colony-forming unit (CFU) counts were reduced by three orders of magnitude on NACP nanocomposite containing 3% DMAHDM.Conclusions: DMAHDM-NACP nanocomposite had good fracture resistance, strong antibacterial potency, and NACP for remineralization (shown in previous studies). The DMAHDM-NACP nanocomposite may be promising for caries-inhibiting dental restorations, and the method of using double agents (DMAHDM and NACP) may have a wide applicability to other dental materials including bonding agents and cements. [ABSTRACT FROM AUTHOR]

The objectives of this study were to: (1) develop a multifunctional adhesive via dimethylaminohexadecyl methacrylate (DMAHDM) and nanoparticles of amorphous calcium phosphate (NACP); and (2) investigate its ability to provide metalloproteinases (MMPs) deactivation and remineralization for long-term dentin bonding durability. DMAHDM and NACP were incorporated into Adper™ Single Bond 2 Adhesive (SB2) at mass fractions of 5% and 20%, respectively. Degree of conversion and contact angle were measured. Endogenous MMP activity of the demineralized dentin beams, Masson's trichrome staining, nano-indentation, microtensile bond strength and interfacial nanoleakage analyses were investigated after 24 h and 3 months of storage aging in artificial saliva. Adding DMAHDM and NACP did not compromise the degree of conversion and contact angle of SB2 (p > 0.05). DMAHDM and NACP incorporation reduced the endogenous MMP activity by 53 %, facilitated remineralization, and increased the Young's modulus of hybrid layer by 49 % after 3 months of aging in artificial saliva, compared to control. For SB2 Control, the dentin bond strength decreased by 38 %, with greater nanoleakage expression, after 3 months of aging (p < 0.05). However, DMAHDM+NACP group showed no loss in bond strength, with much less nanoleakage, after 3 months of aging (p > 0.05). DMAHDM+NACP adhesive greatly reduced MMP-degradation activity in demineralized dentin, induced remineralization at adhesive-dentin interface, and maintained the dentin bond strength after aging, without adversely affecting polymerization and dentin wettability. This new adhesive has great potential to help eliminate secondary caries, prevent hybrid layer degradation, and increase the resin-dentin bond longevity. [ABSTRACT FROM AUTHOR]

Objective Dentin–composite bond failure is caused by factors including hybrid layer degradation, which in turn can be caused by hydrolysis and enzymatic degradation of the exposed collagen in the dentin. The objectives of this study were to investigate a new antibacterial monomer (dimethylaminododecyl methacrylate, DMADDM) as an inhibitor for matrix metalloproteinases (MMPs), and to determine the effects of DMADDM on both soluble recombinant human MMPs (rhMMPs) and dentin matrix-bound endogenous MMPs. Methods Inhibitory effects of DMADDM at six mass% (0.1% to 10%) on soluble rhMMP-8 and rhMMP-9 were measured using a colorimetic assay. Matrix-bound endogenous MMP activity was evaluated in demineralized human dentin. Dentin beams were divided into four groups ( n = 10) and incubated in calcium- and zinc-containing media (control medium); or control medium + 0.2% chlorhexidine (CHX); 5% 12-methacryloyloxydodecylpyridinium bromide (MDPB); or 5% DMADDM. Dissolution of dentin collagen peptides was evaluated by mechanical testing in three-point flexure, loss of dentin mass, and a hydroxyproline assay. Results Use of 0.1% to 10% DMADDM exhibited a strong concentration-dependent anti-MMP effect, reaching 90% of inhibition on rhMMP-8 and rhMMP-9 at 5% DMADDM concentration. Dentin beams in medium with 5% DMADDM showed 34% decrease in elastic modulus (vs. 73% decrease for control), 3% loss of dry dentin mass (vs. 28% loss for control), and significantly less solubilized hydroxyproline when compared with control ( p < 0.05). Significance The new antibacterial monomer DMADDM was effective in inhibiting both soluble rhMMPs and matrix-bound human dentin MMPs. These results, together with previous studies showing that adhesives containing DMADDM inhibited biofilms without compromising dentin bond strength, suggest that DMADDM is promising for use in adhesives to prevent collagen degradation in hybrid layer and protect the resin–dentin bond. [ABSTRACT FROM AUTHOR]

Objectives: Demineralized lesions in tooth enamel around orthodontic brackets are caused by acids from cariogenic biofilm. This study aimed to develop a novel antibacterial orthodontic cement by incorporating a quaternary ammonium monomer dimethylaminododecyl methacrylate (DMADDM) into a commercial orthodontic cement, and to investigate the effects on microcosm biofilm response and enamel bond strength. Methods: DMADDM, a recently-synthetized antibacterial monomer, was incorporated into orthodontic cement at 0%, 1.5%, 3% and 5% mass fractions. Bond strength of brackets to enamel was measured. A microcosm biofilm model was used to measure metabolic activity, lactic acid production, and colony-forming units (CFU) on orthodontic cements. Results: Shear bond strength was not reduced at 3% DAMDDM (p > 0.1), but was slightly reduced at 5% DMADDM, compared to 0% DMADDM. Biofilm viability was substantially inhibited when in contact with orthodontic cement containing 3% DMADDM. Biofilm metabolic activity, lactic acid production, and CFU were much lower on orthodontic cement containing DMADDM than control cement (p < 0.05). Conclusions: Therefore, the novel antibacterial orthodontic cement containing 3% DMADDM inhibited oral biofilms without compromising the enamel bond strength, and is promising to reduce or eliminate demineralization in enamel around orthodontic brackets. [ABSTRACT FROM AUTHOR]

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]

• Resin formulations had a significant effect on ion recharging/re-releasing efficacy. • BT-nCaF 2 had the best combination of mechanical properties and ion recharge/re-release. • Rechargeable nCaF 2 composites had significant recharging potential of F and Ca ions. • After 6 recharge cycles, composites continued F and Ca ions re-release for 42 days. Composite restorations with calcium fluoride nanoparticles (nCaF 2) can remineralize tooth structure through F and Ca ion release. However, the persistence of ion release is limited. The objectives for this study were to achieve long-term remineralization by developing a rechargeable nCaF 2 nanocomposite and investigating the F and Ca recharge and re-release capabilities. Three nCaF 2 nanocomposites were formulated: (1) BT-nCaF 2 :Bisphenol A glycidyl dimethacrylate (BisGMA) and triethylene glycol dimethacrylate (TEGDMA); (2) PE-nCaF 2 :Pyromellitic glycerol dimethacrylate (PMGDM) and ethoxylated bisphenol A dimethacrylate (EBPADMA); (3) BTM-nCaF 2 :BisGMA, TEGDMA, and Bis[2-(methacryloyloxy)ethyl] phosphate (Bis-MEP). All formulations contained 15% nCaF 2 and 55% glass particles. Initial flexural strength and elastic modulus, F and Ca ion release, recharge and re-release were tested and compared to three commercial fluoride-containing materials. BT and BTM nCaF 2 composites were 3–4 times stronger and had elastic modulus 2 times that of resin-modified glass ionomer controls. PE-nCaF 2 had comparable strength to RMGIs. All nCaF 2 composites had significant F and Ca ion release and ion rechargeability. In F and Ca recharging cycles, PE-nCaF 2 had the highest ion recharging capability among nCaF 2 groups, followed by BT-nCaF 2 and BTM-nCaF 2 (p < 0.05). For all recharge cycles, ion release maintained similar levels, demonstrating long-term ion release was possible. Furthermore, after the final recharge cycle, nCaF 2 nanocomposites provided continuous ion release for 42 days without further recharge. Novel nCaF 2 rechargeable nanocomposites exhibited significant F and Ca ion release over multiple recharge cycles, demonstrating continuous long-term ion release. These nanocomposites are promising restorations with lasting remineralization potential. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Calcium phosphate cement (CPC) is promising for dental and craniofacial repairs. Vascularization in bone tissue engineering constructs is currently a major challenge. The objectives of this study were to investigate the prevascularization of macroporous CPC via coculturing human umbilical vein endothelial cells (HUVEC) and human osteoblasts (HOB), and determine the effect of RGD in CPC on microcapillary formation for the first time. Methods: Macroporous CPC scaffold was prepared using CPC powder, chitosan liquid and gas-foaming porogen. Chitosan was grafted with Arg-Gly-Asp (RGD) to biofunctionalize the CPC. HUVEC and HOB were cocultured on macroporous CPC-RGD and CPC control without RGD for up to 42d. The osteogenic and angiogenic differentiation, bone matrix mineral synthesis, and formation of microcapillary-like structures were measured. Results: RGD-grafting in CPC increased the gene expressions of osteogenic and angiogenic differentiation markers than those of CPC control without RGD. Cell-synthesized bone mineral content also increased on CPC-RGD, compared to CPC control (p <0.05). Immunostaining with endothelial marker showed that the amount of microcapillary-like structures on CPC scaffolds increased with time. At 42d, the cumulative vessel length for CPC-RGD scaffold was 1.69-fold that of CPC control. SEM examination confirmed the morphology of self-assembled microcapillary-like structures on CPC scaffolds. Significance: HUVEC+HOB coculture on macroporous CPC scaffold successfully achieved prevascularization. RGD incorporation in CPC enhanced osteogenic differentiation, bone mineral synthesis, and microcapillary-like structure formation. The novel prevascularized CPC-RGD constructs are promising for dental, craniofacial and orthopedic applications. [Copyright &y& Elsevier]

Objectives: Antibacterial bonding agents are promising to combat bacteria and caries at tooth-restoration margins. The objectives of this study were to incorporate new quaternary ammonium methacrylates (QAMs) to bonding agent and determine the effects of alkyl chain length (CL) and quaternary amine charge density on dental plaque microcosm bacteria response for the first time. Methods: Six QAMs were synthesized with CL = 3, 6, 9, 12, 16, 18. Each QAM was incorporated into Scotchbond multi-purpose (SBMP). To determine the charge density effect, dimethylaminododecyl methacrylate (DMAHDM, CL = 16) was mixed into SBMP at mass fraction = 0%, 2.5%, 5%, 7.5%, 10%. Charge density was measured using a fluorescein dye method. Dental plaque microcosm using saliva from ten donors was tested. Bacteria were inoculated on resins. Early-attachment was tested at 4 h. Biofilm colony-forming units (CFU) were measured at 2 days. Results: Incorporating QAMs into SBMP reduced bacteria early-attachment. Microcosm biofilm CFU for CL = 16 was 4 log lower than SBMP control. Charge density of bonding agent increased with DMAHDM content. Bacteria early-attachment decreased with increasing charge density. Biofilm CFU at 10% DMAHDM was reduced by 4 log. The killing effect was similarly-strong against total microorganisms, total streptococci, and mutans streptococci. Conclusions: Increasing alkyl chain length and charge density of bonding agent was shown for the first time to decrease microcosm bacteria attachment and reduce biofilm CFU by 4 orders of magnitude. Novel antibacterial resins with tailored chain length and charge density are promising for wide applications in bonding, cements, sealants and composites to inhibit biofilms and caries. [ABSTRACT FROM AUTHOR]

Implant-related infections are a primary reason for implant failures that affect millions of patients. It is of paramount importance to develop novel implants that possess the dual functions of osteogenesis-promotion and antibacterial activity. The objectives of this study were to: (1) develop novel dual-functional titanium (Ti) implants by combining oxygen non-thermal plasma and covalent bonding of antibacterial organosilicon quaternary ammonium monomers; (2) investigate the physicochemical properties, bioactivity and antibacterial effects of the modified implants for the first time. Surface characteristics of the modified Ti surfaces were tested. Adherence and viability of rat bone marrow-derived stem cells (rBMSCs) on the surface were evaluated. Metabolic activity of biofilm on the surfaces were measured. The stability of the dual-function after 5000 thermal cycles was also evaluated. The presence of chemical bonding between Ti and organosilicon monomers demonstrated covalent immobilization of the antibacterial agents. The water contact angle of the treated Ti surfaces decreased from 70.98 ± 3.68° to 59.86 ± 4.91°. The adhesion and proliferation of rBMSCs on the modified Ti were increased by 40%, compared to control group (P < 0.05). The metabolic level of biofilms on modified Ti were reduced by more than half, compared to control (P < 0.05). The modified Ti implants exhibited cell-promotion and antibacterial stability after thermal cycles. The new dual-functional Ti implant is promising to promote osteogenesis while simultaneously preventing infections. Furthermore, the novel surface modification and processing methods have applicability to enhancing a wide range of other implants to improve bioactivity and combat infections. [Display omitted] • A new long-lasting dual-functional titanium implants was developed. • The novel dual-functional implants have improved hydrophilicity. • The modified Ti implant increased the adhesion and proliferation of cells , and reducing the metabolic level of biofilms. • The dual-functional implants are promising to promote osteogenesis and prevent implant-related infections. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Recent studies developed antibacterial bonding agents and composites containing a quaternary ammonium dimethacrylate (QADM) and nanoparticles of silver (NAg). The objectives of this study were to investigate: (1) the effect of antibacterial primers containing QADM and NAg on the inhibition of Streptococcus mutans impregnated into dentin blocks for the first time, and (2) the effect of QADM or NAg alone or in combination, and the effect of NAg mass fraction, on S. mutans viability in dentin. Methods: Scotchbond Multi-Purpose (SBMP) bonding agent was used. QADM and NAg were incorporated into SBMP primer. Six primers were tested: SBMP primer control, control+10% QADM (mass%), control+0.05% NAg, control+10% QADM+0.05% NAg, control+0.1% NAg, and control+10% QADM+0.1% NAg. S. mutans were impregnated into dentin blocks, then a primer was applied. The viable colony-forming units (CFU) were then measured by harvesting the bacteria in dentin using a sonication method. Results: Control+10% QADM+0.1% NAg had bacteria inhibition zone 8-fold that of control (p <0.05). The sonication method successfully harvested bacteria from dentin blocks. Control+10% QADM+0.1% NAg inhibited S. mutans in dentin blocks, reducing the viable CFU in dentin by three orders of magnitude, compared to control dentin without primer. Using QADM+NAg was more effective than QADM alone. Higher NAg content increased the potency. Dentin shear bond strength was similar for all groups (p >0.1). Significance: Antibacterial primer with QADM and NAg were shown to inhibit the S. mutans impregnated into dentin blocks for the first time. Bonding agent containing QADM and NAg is promising to eradicate bacteria in tooth cavity and inhibit caries. The QADM and NAg may have applicability to other adhesives, cements, sealants and composites. [Copyright &y& Elsevier]