Hard tissue repair and regeneration cost hundreds of billions of dollars annually worldwide, and the need has substantially increased as the population has aged. Hard tissues include bone and tooth structures that contain calcium phosphate minerals. Smart biomaterial-based tissue engineering and regenerative medicine methods have the exciting potential to meet this urgent need. Smart biomaterials and constructs refer to biomaterials and constructs that possess instructive/inductive or triggering/stimulating effects on cells and tissues by engineering the material’s responsiveness to internal or external stimuli or have intelligently tailored properties and functions that can promote tissue repair and regeneration. The smart material-based approaches include smart scaffolds and stem cell constructs for bone tissue engineering; smart drug delivery systems to enhance bone regeneration; smart dental resins that respond to pH to protect tooth structures; smart pH-sensitive dental materials to selectively inhibit acid-producing bacteria; smart polymers to modulate biofilm species away from a pathogenic composition and shift towards a healthy composition; and smart materials to suppress biofilms and avoid drug resistance. These smart biomaterials can not only deliver and guide stem cells to improve tissue regeneration and deliver drugs and bioactive agents with spatially and temporarily controlled releases but can also modulate/suppress biofilms and combat infections in wound sites. The new generation of smart biomaterials provides exciting potential and is a promising opportunity to substantially enhance hard tissue engineering and regenerative medicine efficacy.

A long-time drawback of dental composites is that they accumulate more biofilms and plaques than amalgam and glass ionomer restorative materials. It would be highly desirable to develop a new composite with reduced biofilm growth, while avoiding the non-esthetics of amalgam and low strength of glass ionomer. The objectives of this study were to: (1) develop a protein-repellent composite with reduced biofilms matching amalgam and glass ionomer for the first time; and (2) investigate their protein adsorption, biofilms, and mechanical properties. Five materials were tested: A new composite containing 3% of protein-repellent 2-methacryloyloxyethyl phosphorylcholine (MPC); the composite with 0% MPC as control; commercial composite control; dental amalgam; resin-modified glass ionomer (RMGI). A dental plaque microcosm biofilm model with human saliva as inoculum was used to investigate metabolic activity, colony-forming units (CFU), and lactic acid production. Composite with 3% MPC had flexural strength similar to those with 0% MPC and commercial composite control (p > 0.1), and much greater than RMGI (p < 0.05). Composite with 3% MPC had protein adsorption that was only 1/10 that of control composites (p < 0.05). Composite with 3% MPC had biofilm CFU and lactic acid much lower than control composites (p < 0.05). Biofilm growth, metabolic activity and lactic acid on the new composite with 3% MPC were reduced to the low level of amalgam and RMGI (p > 0.1). In conclusion, a new protein-repellent dental resin composite reduced oral biofilm growth and acid production to the low levels of non-esthetic amalgam and RMGI for the first time. The long-held conclusion that dental composites accumulate more biofilms than amalgam and glass ionomer is no longer true. The novel composite is promising to finally overcome the major biofilm-accumulation drawback of dental composites in order to reduce biofilm acids and secondary caries.

The aims of this study were to: (1) synthesize an anti-biofilm and protein-repellent dental composite by combining 2-methacryloyloxyethyl phosphorylcholine (MPC) with quaternary ammonium dimethylaminohexadecyl methacrylate (DMAHDM); and (2) evaluate the effects of water-aging for 180 days on protein resistance, bacteria-killing ability, and mechanical properties of MPC-DMAHDM composite. MPC and DMAHDM were added into a resin composite. Specimens were stored in distilled water at 37 °C for 1, 30, 90, and 180 days. Mechanical properties were measured in three-point flexure. Protein attachment onto the composite was evaluated by a micro bicinchoninic acid approach. An oral plaque microcosm biofilm model was employed to evaluate oral biofilm viability vs. water-aging time. Mechanical properties of the MPC-DMAHDM composite after 180-day immersion matched those of the commercial control composite. The composite with 3% MPC + 1.5% DMAHDM had much stronger resistance to protein adhesion than control (p < 0.05). MPC + DMAHDM achieved much stronger biofilm-eradicating effects than MPC or DMAHDM alone (p < 0.05). Biofilm colony-forming units on the 3% MPC + 1.5% DMAHDM composite were three orders of magnitude lower than commercial control. The protein-repellent and antibacterial effects were durable and showed no loss in water-aging from 1 to 180 days. The novel MPC-DMAHDM composite possessed strong and durable resistance to protein adhesion and potent bacteria-eradicating function, while matching the load-bearing ability of a commercial dental composite. The novel MPC-DMAHDM composite represents a promising means of suppressing oral plaque growth, acid production, and secondary caries.

Dental caries is prevalent worldwide. Tooth cavity restorations cost more than $46 billion annually in the United States alone. The current generation of esthetic polymeric restorations have unsatisfactory failure rates. Replacing the failed restorations accounts for 50–70% of all the restorations. This article reviewed developments in producing a new generation of bioactive and therapeutic restorations. This includes: Protein-repellent and anti-caries polymeric dental composites, especially the use of 2-methacryloyloxyethyl phosphorylcholine (MPC) and dimethylaminododecyl methacrylate (DMAHDM); protein-repellent adhesives to greatly reduce biofilm acids; bioactive cements to inhibit tooth lesions; combining protein-repellency with antibacterial nanoparticles of silver; tooth surface coatings containing calcium phosphate nanoparticles for remineralization; therapeutic restorations to suppress periodontal pathogens; and long-term durability of bioactive and therapeutic dental polymers. MPC was chosen due to its strong ability to repel proteins. DMAHDM was selected because it had the most potent antibacterial activity when compared to a series of antibacterial monomers. The new generation of materials possessed potent antibacterial functions against cariogenic and periodontal pathogens, and reduced biofilm colony-forming units by up to 4 logs, provided calcium phosphate ions for remineralization and strengthening of tooth structures, and raised biofilm pH from a cariogenic pH 4.5 to a safe pH 6.5. The new materials achieved a long-term durability that was significantly beyond current commercial control materials. This new generation of bioactive and nanostructured polymers is promising for wide applications to provide therapeutic healing effects and greater longevity for dental restorations.