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The limited durability of dentin bonding harshly shortens the lifespan of resin composites restorations. The controlled, dynamic movement of materials through non-contacting forces provides exciting opportunities in adhesive dentistry. We, herein, describe comprehensive investigations of a new dental adhesive with superparamagnetic iron oxide nanoparticles (SPIONs) sensitive to magnetic fields for bonding optimization. This contribution outlines a roadmap of (1) designing and tuning of an adhesive formulation containing SPIONs to enhance penetrability into etched dentin guided by magnetic-field; (2) employing a clinically relevant model of simulated hydrostatic pulpal pressure on the microtensile bond to dentin; and (3) investigating a potential antibacterial effect of the formulated adhesives, and their biocompatibility. SPION-concentration-dependency chemical and mechanical behavior was shown via the degree of conversion, ultimate tensile strength, and micro shear bond strength to dentin. The effects of SPIONs carried on a dental adhesive on the bonding strength to dentin are studied in depth by combining experiments with in vitro simulated model. The results show that under the guided magnetic field, 0.07 wt.% of SPIONs-doped adhesive increased the bond strength that surpasses the reduction caused by hydrostatic pulpal pressure. Using a magnetic guide workflow during the bonding procedures, SPIONs-doped adhesives improved dentin's adhesion without changing adhesives' physicochemical properties. This outcome addresses the key challenge of poor resin infiltration of dentin's conventional total etching during the bonding procedure. The real-time magnetic motion of dental adhesives may open new paths to enhance resin-based restorations' longevity. In this study, dental adhesives containing superparamagnetic iron oxide nanoparticles (SPIONs) were developed to enhance penetrability into dentin guided by a magnetic field. The adhesives were screened for physical, chemical, antibacterial properties, and cytotoxicity. For the first time, simulated pulpal pressure was used concurrently with the magnetic field to simulate a clinical setting. This approach showed that it is feasible to overcome pulpal pressure jeopardization on bond strength when SPIONs and a magnetic field are applied. The magnetic-responsive adhesives had great potential to improve bond strength, opening new paths to enhance resin-based restorations' longevity without affecting adhesives' biological properties. The use of magnetic-responsive particles and magnetically assisted motion is a promising strategy to improve the sealing ability of dental adhesives. [Display omitted] [ABSTRACT FROM AUTHOR]

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]

Recurrent dental caries is one of the main reasons for resin composite restoration failures. This study aimed to: (1) develop a bioactive, low-shrinkage-stress, antibacterial and remineralizing composite and evaluate the sustainability of its antibacterial effect against Streptococcus mutans (S. mutans) biofilms; and (2) evaluate the remineralization and cariostatic potential of the composite containing nanoparticles of amorphous calcium phosphate (NACP) and dimethylaminohexadecyl methacrylate (DMAHDM), using dentin hardness measurement and a biofilm-induced recurrent caries model. The antibacterial and remineralizing low-shrinkage-stress composite consisted of urethane dimethacrylate (UDMA) and triethylene glycol divinylbenzyl ether (TEG-DVBE), 3% DMAHDM and 20% NACP. S. mutans biofilm was used to evaluate antibiofilm activity, before and after 3 months of composite aging in acidic solution. Human dentin was used to develop a recurrent caries biofilm-model. Adding DMAHDM and NACP into low shrinkage-stress composite did not compromise the flexural strength. The low-shrinkage-stress composite with DMAHDM achieved substantial reductions in biofilm colony-forming units (CFU), lactic acid production, and biofilm biomass (p < 0.05). The low-shrinkage-stress DMAHDM+NACP composite exhibited no significant difference in antibacterial performance before and after 3 months of aging, demonstrating long-term antibacterial activity. Under S. mutans biofilm acidic attack, dentin hardness (GPa) was 0.24 ± 0.04 for commercial control, and 0.23 ± 0.03 for experimental control, but significantly higher at 0.34 ± 0.03 for DMAHDM+NACP group (p < 0.05). At an instrumental compliance of 0.33 μm/N, the polymerization shrinkage stress of the new composite was 36% lower than that of a traditional composite (p < 0.05). The triple strategy of antibacterial, remineralization and lower shrinkage-stress has great potential to inhibit recurrent caries and increase restoration longevity. Statement of Significance Polymerization shrinkage stress, masticatory load over time as well as biochemical degradation can lead to marginal failure and secondary caries. The present study developed a new low-shrinkage-stress, antibacterial and remineralizing dental nanocomposite. Polymerization shrinkage stress was greatly reduced, biofilm acid production was inhibited, and tooth dentin mineral and hardness were preserved. The antibacterial composite possessed a long-lasting antibiofilm effect against cariogenic bacteria S. mutans. The new bioactive nanocomposite has the potential to suppress recurrent caries at the restoration margins, protects tooth structures, and increases restoration longevity. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Infection is a main cause of implant failure. Early implant-related infections often occur in the first 4 weeks post-operation. Inhibiting bacterial adhesion and biofilm formation at the early stage and promoting subsequent implant osseointegration are important for implant success. Our previous studies demonstrated that dimethylaminododecyl methacrylate (DMADDM) provided dental materials with antibacterial effects. In the present study, DMADDM and hydroxyapatite (HA) are loaded on to the titanium (Ti) surface via poly dopamine (PDA) self-polymerization. This local DMADDM-delivery Ti is referred as Ti-PHD. Here we report the two-staged capability of Ti-PHD: (1) in the first stage, releasing DMADDM during the high-infection-risk initial period post-implantation for 4 weeks; (2) then in the second stage, enhancing osteogenesis and promoting osseointegration. Ti-PHD has a porous surface with higher average roughness and greater hydrophilicity than pure Ti. Its biocompatibility is verified in vitro and in vivo. During the first 4 weeks of release, both DMADDM remaining on Ti surface and DMADDM released into the soaking medium greatly reduced the adherence and growth of pathogens. This is further confirmed by the prevention of bone destruction in a rat osteomyelitis model. After releasing DMADDM for 4 weeks, Ti-PHD promotes osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) and new bone formation around the implants in vivo. This article represents the first report on the two-staged, time-dependent antibacterial and osteogenesis effects of Ti-PHD, demonstrating its potential for clinical applications to inhibit implant-associated infections. The present study develops a two-staged time-dependent system for local dimethylaminododecyl methacrylate (DMADDM) delivery via Ti implant (referred to as Ti-PHD). DMADDM and hydroxyapatite (HA) are loaded on to the Ti surface with poly dopamine (PDA). Ti-PHD can release DMADDM during the high-risk period of infection in the first stage, and then promote osseointegration and new bone formation in the second stage. This bioactive and therapeutic Ti is promising to inhibit infections and enhance implant success. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Peri-implantitis is the most common risk factor for dental implant failure. Nanostructured ceria (nano-CeO 2) has anti-inflammatory and antibacterial functions, and different shapes of ceria enclosed by specific crystal planes could be an effective approach to enhance intrinsic catalysis. In the present study, the authors developed a novel implant surface-modification strategy by coating different shapes of nano-CeO 2 onto titanium (Ti) surfaces to enhance their antibacterial and anti-inflammatory properties. The objectives of the study were to: (1) develop novel Ti surfaces modified with different shapes of nano-CeO 2 (nanorod, nanocube and nano-octahedron) for peri-implantitis prevention; (2) investigate and compare the inhibition efficacy of different shapes of CeO 2 -modified surfaces against biofilms of peri-implantitis-related pathogens; and (3) evaluate the different CeO 2 -modified surfaces on cell inflammatory response in vitro and in vivo. The results showed that nanorod CeO 2 -modified Ti had more bacteria attachment of Streptococcus sanguinis in the early stage, compared with other CeO 2 -modified Ti (p < 0.05). They all exhibited similarly substantial CFU reductions against peri-implantitis-related biofilms (p > 0.1). Nanocube and nano-octahedron CeO 2 -modified Ti exerted much better anti-inflammatory effects and ROS-scavenging ability than nanorod CeO 2 in vitro (p < 0.05). In vivo , the mean mRNA expression of TNF-α, IL-6 and IL-1β in the tissues around Ti was decreased by the three shapes of nano-CeO 2 ; nano-octahedron CeO 2 showed the strongest anti-inflammatory effect among all groups (p < 0.05). In conclusion, all three types of CeO 2 -modified Ti exerted equally strong antibacterial properties; nano-octahedron CeO 2 -modified Ti had the best anti-inflammatory effect. Therefore, CeO 2 -modified Ti surfaces are highly promising for enhancing antimicrobial functions for dental implants. Novel nano-octahedron CeO 2 coating on Ti had great therapeutic potential for alleviating and eliminating peri-implantitis. Peri-implantitis is the most common risk factor for dental implant failure. Nanostructured ceria (nano-CeO 2) has anti-inflammatory and antibacterial functions, and different shapes of ceria enclosed by specific crystal planes could be an effective approach to enhance intrinsic catalysis. In the present study, we developed a novel implant surface-modification strategy by coating different shapes of nano-CeO 2 onto titanium surfaces to enhance their antibacterial and anti-inflammatory properties for dental implants. In addition, we found that the nano-octahedron CeO 2 coating on titanium would have great therapeutic potential for alleviating and eliminating peri-implantitis. [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]

Abstract Introduction The purpose of this study was to investigate the physical and antibacterial properties of a resin sealer mixed with a quaternary ammonium compound, dimethylaminododecyl methacrylate (DMAHDM) and nanosilver (NAg). Methods A pilot study was completed to determine the highest concentrations of DMAHDM and NAg that did not significantly alter the physical properties (setting time, flow, solubility, and dimensional change) of AH Plus (Dentsply Sirona, York, PA) when added to the sealer. These concentrations were selected to create a modified resin sealer (mAH Plus). A modified direct contact test evaluated antibacterial properties of AH Plus, DMAHDM + AH Plus, NAg + AH Plus, and mAH Plus at days 1, 7, and 14 against Enterococcus faecalis. Results Concentrations of 2.5% DMAHDM and 0.15% NAg were added to AH Plus. The flow of mAH Plus was significantly decreased but still within American National Standards Institute/American Dental Association specifications. There were no significant differences in setting time, solubility, or dimensional change. On day 1, 0.15% NAg + AH Plus, 2.5% DMAHDM + AH Plus, and mAH Plus were significantly more effective against E. faecali s compared with AH Plus (P <.05). On days 7 through 14, 2.5% DMAHDM + AH Plus and mAH Plus continued to be significantly more antibacterial than AH Plus (P <.05). Conclusions The addition of 0.15% NAg and 2.5% DMAHDM did not adversely affect the physical properties of AH Plus, and mAH Plus was significantly more antibacterial against E. faecalis. Highlights • The addition of a quaternary ammonium compound, dimethylaminododecyl methacrylate (DMAHDM) and nanosilver (NAg), provides antibacterial properties for AH plus sealer after setting • The addition of 2.5% DMAHDM and 0.15% NAg to AH Plus did not change the physical properties (flow, setting time, dimensional change, and solubility) of the sealer beyond the specifications required by the American National Standards Institute/American Dental Association. • The new modified AH Plus was significantly more antibacterial against Enterococcus faecalis 14 days after setting compared with AH Plus. [ABSTRACT FROM AUTHOR]

Introduction Metformin is a first-line drug for treating type 2 diabetes that regulates the differentiation of mesenchymal stem cells. Its effects on human dental pulp cells (DPCs) remain unknown. This study aimed to investigate the effects of metformin on the proliferation and differentiation of DPCs. Methods A live/dead viability assay kit was used to examine the effects of metformin on the cell viability of DPCs. Cell proliferation was analyzed using a cell counting kit (CCK-8; Dojindo, Tokyo, Japan). Levels of phosphorylated and unphosphorylated adenosine 5′-monophosphate-activated protein kinase (AMPK) were quantified by Western blot analysis in response to metformin and the AMPK signaling inhibitor Compound C (EMD Chemicals, San Diego, CA). The effects of Compound C on the metformin-induced odontoblast differentiation of DPCs were determined by alkaline phosphatase activity assay and von Kossa staining, and the expression of odontoblastic markers was evaluated by reverse-transcription polymerase chain reaction analysis. Results DPCs exhibited mesenchymal stem cell characteristics using flow cytometry. Different doses of metformin were shown to be cytocompatible with DPCs, yielding >90% cell viability. None of the concentrations of metformin up to 50 μmol/L affected cell proliferation. The Western blot assay showed that DPCs express functional organic cation transporter 1, a transmembrane protein that mediates the intracellular uptake of metformin. Metformin significantly activated the AMPK pathway in a dose-dependent manner. In addition, it stimulated alkaline phosphatase activity; enhanced mineralized nodule formation; and increased the expression of odontoblastic markers including dentin sialophosphoprotein, dentin matrix protein 1, runt-related transcription factor 2, and osteocalcin. Moreover, pretreatment with Compound C, a specific AMPK inhibitor, markedly reversed metformin-induced odontoblastic differentiation and cell mineralization. Conclusions This study shows that metformin can induce DPC differentiation and mineralization in an AMPK-dependent manner and that this well-tolerated antidiabetic drug has potential in regenerative endodontics as well as in other regenerative applications. [ABSTRACT FROM AUTHOR]

In this study, a novel calcium phosphate cement containing gold nanoparticles (GNP-CPC) was developed. Its osteogenic induction ability on human dental pulp stem cells (hDPSCs) was investigated for the first time. The incorporation of GNPs improved hDPSCs behavior on CPC, including better cell adhesion (about 2-fold increase in cell spreading) and proliferation, and enhanced osteogenic differentiation (about 2–3-fold increase at 14 days). GNPs endow CPC with micro-nano-structure, thus improving surface properties for cell adhesion and subsequent behaviors. In addition, GNPs released from GNP-CPC were internalized by hDPSCs, as verified by transmission electron microscopy (TEM), thus enhancing cell functions. The culture media containing GNPs enhanced the cellular activities of hDPSCs. This result was consistent with and supported the osteogenic induction results of GNP-CPC. In conclusion, GNP-CPC significantly enhanced the osteogenic functions of hDPSCs. GNPs are promising to modify CPC with nanotopography and work as bioactive additives thus enhance bone regeneration. [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]

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]

Human induced pluripotent stem cells (hiPSCs) are an exciting cell source with great potential for tissue engineering. Human bone marrow mesenchymal stem cells (hBMSCs) have been used in clinics but are limited by several disadvantages, hence alternative sources of MSCs such as umbilical cord MSCs (hUCMSCs) are being investigated. However, there has been no report comparing hiPSCs, hUCMSCs and hBMSCs for bone regeneration. The objectives of this pilot study were to investigate hiPSCs, hUCMSCs and hBMSCs for bone tissue engineering, and compare their bone regeneration via seeding on biofunctionalized macroporous calcium phosphate cement (CPC) in rat cranial defects. For all three types of cells, approximately 90% of the cells remained alive on CPC scaffolds. Osteogenic genes were up-regulated, and mineral synthesis by cells increased with time in vitro for all three types of cells. The new bone area fractions at 12 weeks (mean ± sd; n = 6) were (30.4 ± 5.8)%, (27.4 ± 9.7)% and (22.6 ± 4.7)% in hiPSC–MSC–CPC, hUCMSC–CPC and hBMSC–CPC respectively, compared to (11.0 ± 6.3)% for control ( p < 0.05). No significant differences were detected among the three types of stem cells ( p > 0.1). New blood vessel density was higher in cell-seeded groups than control ( p < 0.05). De novo bone formation and participation by implanted cells was confirmed via immunohistochemical staining. In conclusion, (1) hiPSCs, hUCMSCs and hBMSCs greatly enhanced bone regeneration, more than doubling the new bone amount of cell-free CPC control; (2) hiPSC–MSCs and hUCMSCs represented viable alternatives to hBMSCs; (3) biofunctionalized macroporous CPC-stem cell constructs had a robust capacity for bone regeneration. [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]

Human embryonic stem cells (hESCs) are an exciting cell source as they offer an unlimited supply of cells that can differentiate into all cell types for regenerative medicine applications. To date, there has been no report on hESCs with calcium phosphate cement (CPC) scaffolds for bone regeneration in vivo. The objectives of this study were to: (i) investigate hESCs for bone regeneration in vivo in critical-sized cranial defects in rats; and (ii) determine the effects of cell seeding and platelets in macroporous CPC on new bone and blood vessel formation. hESCs were cultured to yield mesenchymal stem cells (MSCs), which underwent osteogenic differentiation. Four groups were tested in rats: (i) CPC control without cells; (ii) CPC with hESC-derived MSCs (CPC + hESC-MSC); (iii) CPC with hESC-MSCs and 30% human platelet concentrate (hPC) (CPC + hESC-MSC + 30% hPC); and (iv) CPC + hESC-MSC + 50% hPC. In vitro, MSCs were derived from embryoid bodies of hESCs. Cells on CPC were differentiated into the osteogenic lineage, with highly elevated alkaline phosphatase and osteocalcin expressions, as well as mineralization. At 12 weeks in vivo, the groups with hESC-MSCs and hPC had three times as much new bone as, and twice the blood vessel density of, the CPC control. The new bone in the defects contained osteocytes and blood vessels, and the new bone front was lined with osteoblasts. The group with 30% hPC and hESC-MSCs had a blood vessel density that was 49% greater than the hESC-MSC group without hPC, likely due to the various growth factors in the platelets enhancing both new bone and blood vessel formation. In conclusion, hESCs are promising for bone tissue engineering, and hPC can enhance new bone and blood vessel formation. Macroporous CPC with hESC-MSCs and hPC may be useful for bone regeneration in craniofacial and orthopedic applications. [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: Antibacterial and remineralizing dental composites and adhesives were recently developed to inhibit biofilm acids and combat secondary caries. It is not clear what effect these materials will have on dental pulps in vivo. The objectives of this study were to investigate the antibacterial and remineralizing restorations in a rat tooth cavity model, and determine pulpal inflammatory response and tertiary dentin formation. Nanoparticles of amorphous calcium phosphate (NACP) and antibacterial dimethylaminododecyl methacrylate (DMADDM) were synthesized and incorporated into a composite and an adhesive. Occlusal cavities were prepared in the first molars of rats and restored with four types of restoration: control composite and adhesive; control plus DMADDM; control plus NACP; and control plus both DMADDM and NACP. At 8 or 30days, rat molars were harvested for histological analysis. For inflammatory cell response, regardless of time periods, the NACP group and the DMADDM+NACP group showed lower scores (better biocompatibility) than the control group (p =0.014 for 8days, p =0.018 for 30days). For tissue disorganization, NACP and DMADDM+NACP had better scores than the control (p =0.027) at 30days. At 8days, restorations containing NACP had a tertiary dentin thickness (TDT) that was five- to six-fold that of the control. At 30days, restorations containing NACP had a TDT that was four- to six-fold that of the control. In conclusion, novel antibacterial and remineralizing restorations were tested in rat teeth in vivo for the first time. Composite and adhesive containing NACP and DMADDM exhibited milder pulpal inflammation and much greater tertiary dentin formation than the control adhesive and composite. Therefore, the novel composite and adhesive containing NACP and DMADDM are promising as a new therapeutic restorative system to not only combat oral pathogens and biofilm acids as shown previously, but also facilitate the healing of the dentin–pulp complex. [Copyright &y& Elsevier]

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: There has been little research on the seeding of human umbilical cord mesenchymal stem cells (hUCMSCs) in three-dimensional scaffolds for muscle tissue engineering. The objectives of this study were: (i) to seed hUCMSCs in a fibrin hydrogel containing fast-degradable microbeads (dMBs) to create macropores to enhance cell viability; and (ii) to investigate the encapsulated cell proliferation and myogenic differentiation for muscle tissue engineering. Mass fractions of 0–80% of dMBs were tested, and 35% of dMBs in fibrin was shown to avoid fibrin shrinkage while creating macropores and promoting cell viability. This construct was referred to as “dMB35”. Fibrin without dMBs was termed “dMB0”. Microbead degradation created macropores in fibrin and improved cell viability. The percentage of live cells in dMB35 reached 91% at 16days, higher than the 81% in dMB0 (p <0.05). Live cell density in dMB35 was 1.6-fold that of dMB0 (p <0.05). The encapsulated hUCMSCs proliferated, increasing the cell density by 2.6 times in dMB35 from 1 to 16days. MTT activity for dMB35 was substantially higher than that for dMB0 at 16days (p <0.05). hUCMSCs in dMB35 had high gene expressions of myotube markers of myosin heavy chain 1 (MYH1) and alpha-actinin 3 (ACTN3). Elongated, multinucleated cells were formed with positive staining of myogenic specific proteins including myogenin, MYH, ACTN and actin alpha 1. Moreover, a significant increase in cell fusion was detected with myogenic induction. In conclusion, hUCMSCs were encapsulated in fibrin with degradable microbeads for the first time, achieving greatly enhanced cell viability and successful myogenic differentiation with formation of multinucleated myotubes. The injectable and macroporous fibrin–dMB–hUCMSC construct may be promising for muscle tissue engineering applications. [Copyright &y& Elsevier]

Abstract: The need for bone repair has increased as the population ages. The objectives of this study were to (1) develop a novel biofunctionalized and macroporous calcium phosphate cement (CPC) containing alginate–fibrin microbeads encapsulating human umbilical cord mesenchymal stem cells (hUCMSC) and, for the first time, (2) investigate hUCMSC proliferation and osteogenic differentiation inside the CPC. A macroporous CPC was developed using calcium phosphate powder, chitosan, and a gas-foaming porogen. Five types of CPC were fabricated: a CPC control, CPC+0.05% fibronectin (Fn), CPC+0.1% Fn, CPC+0.1% arginine–glycine–aspartate (RGD), and CPC+0.1% Fn+0.1% RGD. Alginate–fibrin microbeads containing 106 hUCMSC per ml were encapsulated in the CPC paste. After the CPC had set, the degradable microbeads released hUCMSC within it. The hUCMSC proliferated inside the CPC, with the cell density after 21days being 4-fold that on day1. CPC+0.1% RGD had the highest cell density, which was 4-fold that of the CPC control. The released cells differentiated along the osteogenic lineage and synthesized bone mineral. The hUCMSC inside the CPC+0.1% RGD construct expressed the genes alkaline phosphatase, osteocalcin and collagen I, at twice the level of the CPC control. Mineral synthesis by hUCMSC inside the CPC+0.1% RGD construct was 2-fold that in the CPC control. RGD and Fn incorporation in the CPC did not compromise its strength, which matched the reported strength of cancellous bone. In conclusion, degradable microbeads released hUCMSC which proliferated, differentiated and synthesized minerals inside the macroporous CPC. The CPC with RGD greatly enhanced cell function. The novel biofunctionalized and macroporous CPC–microbead–hUCMSC construct is promising for bone tissue engineering applications. [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: Fibrous scaffolds are promising for tissue engineering because of the high surface area and fibrous features mimicking the extracellular matrix in vivo. Calcium phosphate cements (CPCs) can be injected and self-set in the bone defect. A literature search revealed that there have been no reports on stem cell seeding on CPC containing electrospun submicron fibers. The objective of this study was to investigate for the first time the effects of electrospun fibers in CPC on mechanical properties and human umbilical cord mesenchymal stem cell (hUCMSC) proliferation, osteogenic differentiation and mineralization. Poly(d,l-lactide-co-glycolide) fibers were made via an electrospinning technique to yield an average fiber diameter of 650nm. The fibers were incorporated into CPC consisting of tetracalcium phosphate, dicalcium phosphate anhydrous and chitosan lactate. Fiber volume fractions were 0%, 2.5%, 5% and 10%. CPC with 10% fibers had a flexural strength that was twice that of CPC without fibers, and a work-of-fracture (toughness) that was an order of magnitude larger than that of CPC without fibers. hUCMSCs proliferated rapidly and synthesized bone minerals when attached to the electrospun fiber–CPC scaffolds. Alkaline phosphatase, osteocalcin and collagen I expressions of hUCMSCs were doubled, while mineralization was increased by 40%, when fiber volume fraction in CPC was increased from 0% to 10%. The enhanced cell function was attributed to the high surface area and biomimetic features of the fiber–CPC scaffold. In conclusion, incorporating submicron fibers into CPC greatly improved the strength and toughness of the CPC. Creating submicron fibrous features in CPC was a useful method for enhancing the osteogenic differentiation and mineralization of stem cells. The novel electrospun fiber–CPC–hUCMSC construct is promising for stem cell delivery and bone tissue engineering. [Copyright &y& Elsevier]

Abstract: Due to its injectability and excellent osteoconductivity, calcium phosphate cement (CPC) is highly promising for orthopedic applications. However, a literature search revealed no report on human bone marrow mesenchymal stem cell (hBMSC) encapsulation in CPC for bone tissue engineering. The aim of this study was to encapsulate hBMSCs in alginate hydrogel beads and then incorporate them into CPC, CPC–chitosan and CPC–chitosan–fiber scaffolds. Chitosan and degradable fibers were used to mechanically reinforce the scaffolds. After 21days, that the percentage of live cells and the cell density of hBMSCs inside CPC-based constructs matched those in alginate without CPC, indicating that the CPC setting reaction did not harm the hBMSCs. Alkaline phosphate activity increased by 8-fold after 14days. Mineral staining, scanning electron microscopy and X-ray diffraction confirmed that apatitic mineral was deposited by the cells. The amount of hBMSC-synthesized mineral in CPC–chitosan–fiber matched that in CPC without chitosan and fibers. Hence, adding chitosan and fibers, which reinforced the CPC, did not compromise hBMSC osteodifferentiation and mineral synthesis. In conclusion, hBMSCs were encapsulated in CPC and CPC–chitosan–fiber scaffolds for the first time. The encapsulated cells remained viable, osteodifferentiated and synthesized bone minerals. These self-setting, hBMSC-encapsulating CPC-based constructs may be promising for bone tissue engineering applications. [ABSTRACT FROM AUTHOR]