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.

Oral diseases such as tooth caries, periodontal diseases, endodontic infections, etc., are prevalent worldwide. The heavy burden of oral infectious diseases and their consequences on the patients’ quality of life indicates a strong need for developing effective therapies. Advanced understandings of such oral diseases, e.g., inflammatory periodontal lesions, have raised the demand for antibacterial therapeutic strategies, because these diseases are caused by viruses and bacteria. The application of antimicrobial photodynamic therapy (aPDT) on oral infectious diseases has attracted tremendous interest in the past decade. However, aPDT had a minimal effect on the viability of organized biofilms due to the hydrophobic nature of the majority of the photosensitizers (PSs). Therefore, novel nanotechnologies were rapidly developed to target the delivery of hydrophobic PSs into microorganisms for the antimicrobial performance improvement of aPDT. This review focuses on the state-of-the-art of nanomaterials applications in aPDT against oral infectious diseases. The first part of this article focuses on the cutting-edge research on the synthesis, toxicity, and therapeutic effects of various forms of nanomaterials serving as PS carriers for aPDT applications. The second part discusses nanomaterials applications for aPDT in treatments of oral diseases. These novel bioactive nanomaterials have demonstrated great potential to serve as carriers for PSs to substantially enhance the PDT therapeutic effects. Furthermore, the novel aPDT applications not only have exciting therapeutic potential to inhibit bacterial plaque-initiated oral diseases, but also have a wide applicability to other biomedical and tissue engineering applications.

The objectives of this study were to develop a bioactive dental composite and investigate the effects of 2-methacryloyloxyethyl phosphorylcholine (MPC) and dimethylaminohexadecyl methacrylate (DMAHDM) in Class V composite on mechanical properties, water sorption, protein adsorption, and inhibition of four species of periodontitis-related biofilms for the first time. The resin consisted of ethoxylated bisphenol A dimethacrylate (EBPADMA) and pyromellitic glycerol dimethacrylate (PMGDM). DMAHDM, MPC and nanoparticles of amorphous calcium phosphate (NACP) were incorporated into the resin. Four species (Porphyromonas gingivalis, Prevotella intermedia, Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum) were tested for biofilm colony-forming units (CFU), live/dead, metabolic activity, and polysaccharide production. The results showed that adding DMAHDM and MPC to the composite did not compromise the mechanical properties (p>0.1), with acceptable water sorption values. Composite with 3% MPC reduced protein adsorption to 1/9 that of a commercial composite (p<0.05). For all four species, the composite with 3% DMAHDM+3% MPC had much greater reduction in biofilms than using DMAHDM or MPC alone (p<0.05). Biofilm CFU was reduced by about 4 orders of magnitude via 3% DMAHDM+3% MPC, compared to control. The inhibition efficacy for the four species was: P. gingivalis>P intermedia=A. actinomycetemcomitans>F. nucleatum. In conclusion, a novel bioactive composite with 3% DMAHDM and 3% MPC achieved the greatest reduction in biofilm growth, metabolic activity and polysaccharide of four periodontal pathogens. The new composite is promising for Class V restorations especially with subgingival margins to inhibit periodontal pathogens, combat periodontitis and protect the periodontium.

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The objectives of this study were to: (1) develop a new bioactive dental bonding agent with nanoparticles of amorphous calcium phosphate and dimethylaminohexadecyl methacrylate for tooth root caries restorations and endodontic applications, and (2) investigate biofilm inhibition by the bioactive bonding agent against eight species of periodontal and endodontic pathogens for the first time. Bonding agent was formulated with 5 % of dimethylaminohexadecyl methacrylate. Nanoparticles of amorphous calcium phosphate at 30 wt% was mixed into adhesive. Eight species of biofilms were grown on resins: Porphyromonas gingivalis, Prevotella intermedia, Prevotella nigrescens, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Parvimonas micra, Enterococcus faecalis, Enterococcus faecium. Colony-forming units, live/dead assay, biomass, metabolic activity and polysaccharide of biofilms were determined. The results showed that adding dimethylaminohexadecyl methacrylate and nanoparticles of amorphous calcium phosphate into bonding agent did not decrease dentin bond strength (P > 0.1). Adding dimethylaminohexadecyl methacrylate reduced the colony-forming units of all eight species of biofilms by nearly three orders of magnitude. The killing efficacy of dimethylaminohexadecyl methacrylate resin was: P. gingivalis > A. actinomycetemcomitans > P. intermedia > P. nigrescens > F. nucleatum > P. micra > E. faecalis > E. faecium. Dimethylaminohexadecyl methacrylate resin had much less biomass, metabolic activity and polysaccharide of biofilms than those without dimethylaminohexadecyl methacrylate (P < 0.05). In conclusion, a novel dental adhesive was developed for root caries and endodontic applications, showing potent inhibition of biofilms of eight species of periodontal and endodontic pathogens, and reducing colony-forming units by three orders of magnitude. The bioactive adhesive is promising for tooth root restorations to provide subgingival margins with anti-periodontal pathogen capabilities, and for endodontic sealer applications to combat endodontic biofilms.