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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]

The objectives of this study were to incorporate iron oxide nanoparticles (IONPs) into calcium phosphate cement (CPC) to enhance bone engineering, and to investigate the effects of IONPs as a liquid or powder on stem cells using IONP-CPC scaffold for the first time. IONP-CPCs were prepared by adding 1% IONPs as liquid or powder. Human dental pulp stem cells (hDPSCs) were seeded. Subcutaneous implantation in mice was investigated. IONP-CPCs had better cell spreading, and greater ALP activity and bone mineral synthesis, than CPC control. Subcutaneous implantation for 6 weeks showed good biocompatibility for all groups. In conclusion, incorporating IONPs in liquid or powder form both substantially enhanced hDPSCs on IONP-CPC scaffold and exhibited excellent biocompatibility. IONP incorporation as a liquid was better than IONP powder in promoting osteogenic differentiation of hDPSCs. Incorporating IONPs and chitosan lactate together in CPC enhanced osteogenesis of hDPSCs more than using either alone. Iron oxide nanoparticles (IONPs) which can be incorporated as liquid or powder can enhance the bioactivity of calcium phosphate cements (CPCs). However, incorporation methods can affect the bioactivity of the final IONP-CPC. Although both methods can result in substantially enhancement of CPCs, incorporation as liquid seemed better than powder in promoting bioactivity. And incorporating IONPs and chitosan lactate together enhanced CPCs better than using either alone. The effects were attributed to the chemical composition, the distribution of IONPs, the scaffold surface properties, and the magnetism effects. Therefore, incorporation methods can affect the bioactivity of IONP-CPC. Suitable incorporation method is promising to achieve better osteogenesis effects. Unlabelled Image [ABSTRACT FROM AUTHOR]

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]