Antibacterial bonding agents could combat recurrent caries at the tooth-composite margins. The objectives of this study were to develop novel antibacterial dentin primers containing quaternary ammonium dimethacrylate (QADM) and nanoparticles of silver (NAg), and to investigate the effects on dentin bond strength and dental plaque microcosm biofilms for the first time. Scotchbond Multi-Purpose ("SBMP") bonding agent was used. QADM and NAg were incorporated into SBMP primer, yielding 4 primers: SBMP primer (control), control + 10% QADM (mass), control + 0.05% NAg, and control + 10% QADM + 0.05% NAg. Human saliva was collected to grow microcosm biofilms. The NAg particle size (mean ± SD; n = 100) was 2.7 ± 0.6 nm. Dentin shear bond strengths (n = 10) with human third molars were approximately 30 MPa for all groups (p > 0.1). QADMNAg-containing primer increased the bacteria inhibition zone by 9-fold, compared with control primer (p < 0.05). QADM-NAg-containing primer reduced lactic acid production and colony-forming units of total micro-organisms, total streptococci, and mutans streptococci by an order of magnitude. In conclusion, novel QADM-NAg-containing primers were strongly antibacterial without compromising dentin bond strength, and hence are promising to inhibit biofilms and secondary caries. The processing method of incorporating QADM and NAg together into the same primer produced the strongest antibacterial effect, which could have a wide applicability to other bonding systems.KEY WOrDs: antibacterial dentin primer, quaternary ammonium salt, dental biomaterials, bond strength, dental plaque microcosm biofilm, caries inhibition.

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. Ng was synthesized by dissolving Ag 2-ethylhexanoate salt in 2-(tertbutylamino)ethyl methacrylate. Mechanical properties were measured in three-point flexure with bars of 2×2×25 mm (n = 6). Composite disks (diameter = 9 mm, thickness = 2 mm) 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.

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

Objectives Antibacterial bonding agents are promising to hinder the residual and invading bacteria at the tooth-restoration interfaces. The objectives of this study were to develop an antibacterial bonding agent by incorporation of quaternary ammonium dimethacrylate (QADM) and nanoparticles of silver (NAg), and to investigate the effect of QADM-NAg adhesive and primer on dentin bond strength and plaque microcosm biofilm response for the first time. Methods Scotchbond Multi-Purpose adhesive and primer were used as control. Experimental adhesive and primer were made by adding QADM and NAg into control adhesive and primer. Human dentin shear bond strengths were measured (n = 10). 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 assay (n = 6). Results Adding QADM and NAg into adhesive and primer did not compromise the dentin shear bond strength which ranged from 30 to 35 MPa (p > 0.1). Scanning electron microscopy (SEM) examinations revealed numerous resin tags, which were similar for the control and the QADM and NAg groups. Adding QADM or NAg markedly reduced the biofilm viability, compared to adhesive control. QADM and NAg together in the adhesive had a much stronger antibacterial effect than using each agent alone (p < 0.05). Adding QADM and NAg in both adhesive and primer had the strongest antibacterial activity, reducing metabolic activity, CFU, and lactic acid by an order of magnitude, compared to control. Significance Without compromising dentin bond strength and resin tag formation, the QADM and NAg containing adhesive and primer achieved strong antibacterial effects against microcosm biofilms for the first time. QADM-NAg adhesive and primer are promising to combat residual bacteria in tooth cavity and invading bacteria at the margins, thereby to inhibit secondary caries. QADM and NAg incorporation may have a wide applicability to other dental bonding systems.

The objectives of this study were to synthesize new quaternary ammonium methacrylates (QAMs) with systematically varied alkyl chain lengths (CL) and to investigate, for the first time, the CL effects on antibacterial efficacy, cytotoxicity, and dentin bond strength of bonding agents. QAMs were synthesized with CL of 3 to 18 and incorporated into Scotchbond Multi-Purpose (SBMP) bonding agent. The cured resins were inoculated with Streptococcus mutans. Bacterial early attachment was investigated at 4 hrs. Biofilm colonyforming units (CFU) were measured after 2 days. With CL increasing from 3 to 16, the minimum inhibitory concentration and minimum bactericidal concentration were decreased by 5 orders of magnitude. Incorporating QAMs into SBMP reduced bacterial early attachment, with the least colonization at CL = 16. Biofilm CFU for CL = 16 was 4 log lower than SBMP control (p < .05). All groups had similar dentin bond strengths (p > .1). The new antibacterial materials had fibroblast/ odontoblast viability similar to that of commercial controls. In conclusion, increasing the chain length of new QAMs in bonding agents greatly increased the antibacterial efficacy. A reduction in Streptococcus mutans biofilm CFU by 4 log could be achieved, without compromising bond strength and cytotoxicity. New QAM-containing bonding agents are promising for a wide range of restorations to inhibit biofilms.KEY WOrDs: antibacterial activity, Streptococcus mutans, quaternary ammonium compounds, dentin bonding, fibroblasts, odontoblasts. (Mjör and Toffeneti, 2000;Sakaguchi, 2005). Replacing failed restorations accounts for 50% to 70% of all restorations performed (Frost, 2002;Bagramian et al., 2009). Biofilm acids could lead to caries (ten Cate, 2006); hence antibacterial resins were developed to inhibit biofilms (Imazato et al., 1999;Imazato, 2003;Beyth et al., 2006;Namba et al., 2009;Cheng et al., 2012a). Indeed, previous studies investigated the copolymerization of quaternary ammonium methacrylates (QAMs) to develop antibacterial resins (Imazato, 2003;Li et al., 2009;Xie et al., 2011;Antonucci et al., 2012;Xu et al., 2012;Zhang et al., 2012).Composites are the principal materials for tooth-cavity restorations (Ferracane, 2011) which are bonded in cavities via adhesives (Ferracane et al., 2010;Spencer et al., 2010;Pashley et al., 2011). Residual bacteria could exist in the prepared cavity, and microleakage could allow bacteria to invade the tooth-restoration interfaces. Therefore, it is beneficial for primer/ adhesive to be antibacterial (Imazato et al., 1998;Imazato, 2003;Li et al., 2009;Hiraishi et al., 2010;Cheng et al., 2012b). Quaternary ammonium can cause bacteria lysis by binding to membranes (Beyth et al., 2006). A previous study revealed that long polymeric chains with positive charges and hydrophobicity effectively killed bacteria (Lin et al., 2002). When the alkyl chain length (CL) was increased, the hydrophobicity increased, thereby enhancing its propensity to penetrate the hydrophobic bacterial membrane (Tiller...

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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.

Tissue engineering is promising to meet the increasing need for bone regeneration. Nanostructured calcium phosphate (CaP) biomaterials/scaffolds are of special interest as they share chemical/crystallographic similarities to inorganic components of bone. Three applications of nano-CaP are discussed in this review: nanostructured calcium phosphate cement (CPC); nano-CaP composites; and nano-CaP coatings. The interactions between stem cells and nano-CaP are highlighted, including cell attachment, orientation/morphology, differentiation and in vivo bone regeneration. Several trends can be seen: (i) nano-CaP biomaterials support stem cell attachment/proliferation and induce osteogenic differentiation, in some cases even without osteogenic supplements; (ii) the influence of nano-CaP surface patterns on cell alignment is not prominent due to non-uniform distribution of nano-crystals; (iii) nano-CaP can achieve better bone regeneration than conventional CaP biomaterials; (iv) combining stem cells with nano-CaP accelerates bone regeneration, the effect of which can be further enhanced by growth factors; and (v) cell microencapsulation in nano-CaP scaffolds is promising for bone tissue engineering. These understandings would help researchers to further uncover the underlying mechanisms and interactions in nano-CaP stem cell constructs in vitro and in vivo, tailor nano-CaP composite construct design and stem cell type selection to enhance cell function and bone regeneration, and translate laboratory findings to clinical treatments.