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.

Objectives The widespread incidence of recurrent caries highlights the need for improved dental restorative materials. The objective of this study was to synthesize low viscosity ionic dimethacrylate monomers (IDMAs) that contain quaternary ammoniums groups (antimicrobial functionalities) and are compatible with existing dental dimethacrylate-based monomers. Such monomers have the potential to copolymerize with other methacrylate monomers and produce antibacterial polymers. Methods Two monomers (IDMA-1 and IDMA-2) were synthesized using the Menschutkin reaction and incorporated at 0% to 30% (by mass) into a 1:1 (by mass) bisphenol A glycerolate dimethacrylate (BisGMA):triethylene glycol dimethacrylate (TEGDMA) resin. Resin viscosity was quantified using rheology, and polymer degree of conversion (DC) and surface charge density were measured using Fourier transform infrared spectroscopy (FTIR) and fluorescein binding, respectively. Effects of IDMA-1 on initial attachment of Streptococcus mutans and on viability and enzymatic activity (formazan reduction) of RAW 264.7 macrophage-like cells were quantified. Results IDMA-1 and IDMA-2 were prepared and characterized. IDMA-1 was miscible with BisGMA:TEGDMA and slightly increased the resin viscosity and DC. As expected, polymeric surface charge density increased with increasing IDMA-1. Incorporation of 10% IDMA-1 into BisGMA:TEGDMA reduced bacterial colonization without affecting viability or enzymatic activity of mammalian cells. Increasing IDMA-1 up to 30% had no additional effect on bacterial coverage, but ≥ 20% IDMA-1 significantly reduced macrophage density, viability, and enzymatic activity. Leachables from polymers containing IDMA-1 were not cytotoxic. Significance The Menschutkin reaction provides a facile, convenient means to synthesize new monomers with quaternary ammonium groups for dental and medical applications.

Cells are known to sense and respond to the physical properties of their environment and those of tissue scaffolds. Optimizing these cell-material interactions is critical in tissue engineering. In this work, a simple and inexpensive combinatorial platform was developed to rapidly screen three-dimensional (3D) tissue scaffolds and was applied to screen the effect of scaffold properties for tissue engineering of bone. Differentiation of osteoblasts was examined in poly(ethylene glycol) hydrogel gradients spanning a 30-fold range in compressive modulus (≈ 10 kPa to ≈ 300 kPa). Results demonstrate that material properties (gel stiffness) of scaffolds can be leveraged to induce cell differentiation in 3D culture as an alternative to biochemical cues such as soluble supplements, immobilized biomolecules and vectors, which are often expensive, labile and potentially carcinogenic. Gel moduli of ≈ 225 kPa and higher enhanced osteogenesis. Furthermore, it is proposed that material-induced cell differentiation can be modulated to engineer seamless tissue interfaces between mineralized bone tissue and softer tissues such as ligaments and tendons. This work presents a combinatorial method to screen biological response to 3D hydrogel scaffolds that more closely mimics the 3D environment experienced by cells in vivo.

Facile synthesis and detailed characterization of photopolymerizable and biocompatible poly(ethylene glycol) dimethacrylates (PEGDM) and poly(ethylene glycol) urethane-dimethacrylates (PEGUDM) are described. Poly(ethylene glycol)s of various molecular masses (M(n) = 1000 to 8000 g/mol) were reacted with methacrylic anhydride or with 2-isocyanatoethyl methacrylate to form PEGDMs and PEGUDMs, respectively. PEGDMs were also prepared by a microwave-assisted route to achieve fast reaction conversions under solvent free conditions. Combined analyses of (1)H NMR and MALDI-TOF MS confirmed the formation of prepolymers of high purity and narrow mass distribution (PD < 1.02). Aqueous solutions of the PEGDMs and PEGUDMs (10% and 20% by mass fraction) were photopolymerized to yield hydrogels. Bovine chondrocytes, seeded in the hydrogels, were used to assess the biocompatibility. Preliminary rheology and uniaxial compression measurements showed varied mechanical response, and biocompatibility studies showed that cells are completely viable in both types of hydrogels after two weeks.