Advances in Dental Materials

NanodentistryNANOTECHNOLOGY HAS INDUCED THE GENERATION OF INNOVATIVE AND COST-EFFECTIVE DENTAL MATERIALS AND DEVICES, ENABLED THE UNDERSTANDING OF BIOMECHANICAL PROPERTIES OF ENAMEL (E.G., FRACTURE BEHAVIOR AND CRACK PROPAGATION), AND CONTRIBUTED TO THE IMPROVEMENT OF BONE-TISSUE REGENERATION AS WELL AS THE DIAGNOSIS AND PREVENTION OF PATHOLOGIES

NANODENTISTRY IS REVIEWED HERE FROM THE SCIENTIFIC AND TECHNOLOGICAL PERSPECTIVES BY FOLLOWING A PROPERTY–FUNCTION–APPLICATION BASIS THAT ADDRESSES MOST OF THE RECENT ADVANCES ON THE USE OF

( I ) ) . ., , , POLYMERIC E G POLYETHYLENE GLYCOL SOLID LIPIDS, , (NANOGELS DENDRIMERS CHITOSAN;

( II ) ) . ., , , (METALLIC E G SILVER GOLD COPPER ;(III ) - ) . ., , , INORGANIC NANO BASED MATERIALS E G ZIRCONIA SILICA

, , , TITANIUM DIOXIDE HYDROXYAPATITE QUANTUM DOTS(NANOCARBONS.

Antimicrobial Dental Nanomaterials

SILVER NANOPARTICLES (AGNPS)ZINC OXIDE-BASED NANOPARTICLES (ZNONPS)TITANIUM DIOXIDE-BASED NANOPARTICLES (TIO2NPS)COPPER-BASED NANOPARTICLES (CUNPS)CHITOSAN NANOPARTICLESNANOMATERIALS AND QUATERNARY AMMONIUM COMPOUNDS (QACS)

Silver Nanoparticles (AgNPs)

SILVER-BASED NANOMATERIALS ARE EFFECTIVE AGAINST BIOFILMS BECAUSE THEY CAN ATTACK MULTIPLE SITES WITHIN THE CELL AT A VERY LOW CONCENTRATION (0.5–1.0%) TO PREVENT BACTERIAL GROWTH ON THE ANTIBACTERIAL MECHANISM OF SILVER NANOPARTICLES, PROTEOGLYCANS PRESENT INSIDE THE BACTERIA CELLS AND ON THE MEMBRANE APPEAR TO ACT AS BINDING SITES FOR AGNPS AND SILVER IONS . FURTHERMORE, SILVER IONS CAN INTERACT WITH SULFURYL GROUPS DURING PROTEIN SYNTHESIS, THEREBY INTERFERING WITH THE REPLICATION OF BACTERIAL DNA

Silver Nanoparticle (AgNPs)Activity against Bacteria

In dentistry, fundamental aspects must be considered during the preparation of AgNPs, such as:

(i )diffusion of nanoparticles into a plaque biofilm exhibits an inverse relationship between size and effectiveness, such that nanoparticles larger than 50 nm cannot penetrate the biofilm ; and (ii) negatively charged nanoparticles have difficulty in diffusing through the biofilm, possibly due to the presence of carboxyl and phosphoryl groups on the bacteria surface that render the cell surface electronegative

Zinc Oxide-Based Nanoparticles (ZnONPs)Zinc has been also used in dentistry for many years as

the majorfiller component of dental cements. Zinc ions exhibit effective antibacterial activity and this effect is higher when zinc oxide is present as nanoparticles. The bactericidal effect of ZnONPs may be attributed to their ability to interact with the cell membrane of several bacterial species; Zn strongly binds to lipids and proteins, changing the osmotic balance and increasing membrane permeability

Titanium Dioxide-Based Nanoparticles (TiO2NPs)TiO2NPs undergo photocatalysis when exposed to near-UV and UVA radiation, producing reactive oxygen species (ROS: mainly H2O2 and OH) which alter the osmotic equilibrium of bacteria. Furthermore, TiO2NPs can interfere with phosphorylation, thereby causing oxidative cell death.

However, a key aspect to be elucidated is the fact that TiO2, even when non-irradiated, may exhibit antibacterial activity through an unknown mechanism.

Copper-Based Nanoparticles (CuNPs)

Similar to most of the nanoparticles, the mechanism of action of CuNPs remains obscure.However, a possible explanation is based on the fact that Cu can bind to amine and carboxylic groups on the surface of the microorganism and cause modifications to their cell membranes.

In addition, the high concentration of copper ions may also cause the formation of reactive species that alter protein synthesis and DNA replication of the microorganisms.

Chitosan NanoparticlesChitosan, a long polymer chain characterized by randomly arranged N-acetyl-glucosamine and glucosamine residues, has recently been introduced as a potential antibacterial agent for dental applications . The antibacterial effect of chitosan may be attributed to its chemical structure, with the presence of deacetylated C2 amino groups which become protonated and positively charged at pH <6.5. Thus, chitosan binds to the membrane of bacterial cells leading to:

( i ) increase in membrane permeability with a concomitant increase in the outward fl ow of ions and proteins from the

microbial cell;( ii )inhibition of mRNA transcription and alteration of

protein translation owing to binding of chitosan to the DNA of several microorganisms

Nanomaterials and Quaternary Ammonium Compounds (QACs)Nanostructured materials containing low concentrations

(1%) of QACs have been recently used in dentistry in view of their antibacterial effects against several species including S. mutans andLactobacillus casei.

The antibacterial mechanism of QACs has not yet been fully elucidated. It is believed that QAC salts may act as highly-active cationic agents, causing adsorption of positively charged polymers on the bacterial cell membrane. Such interaction would cause significant changes in membrane permeability that eventually result in complete lysis of the bacteria cell membrane

Nanomaterials for Therapeutic Dentistry

• Polymeric Nanoparticles• Carbon Nanomaterials and Quantum

Dots• Gold Nanoparticles

Polymeric NanoparticlesNanoparticles also represent a promising strategy for selective and controlled drug delivery into cells and tissues, thus inducing a uniform drug concentration at the site of injury, facilitatingdiffusion of drugs into tumors, and reducing side-effects.

In dentistry, antitumor nanoparticles loaded with cisplatin distributed on polyethylene glycol-poly(glutamic acid) showed effective action against oral squamous cell carcinoma, but with much less renal toxicity compared to the use of cisplatin alone.

Schematic Illustration Representing the Current Use and Perspectives on the Use of Nanomaterials on Therapeutic Dentistry

Carbon Nanomaterials and Quantum DotsNanocarbon materials (NCs: carbon nanotubes, graphene, and fullerene) have been widely used in medicine in view of their ability to improve the mechanical properties of specific bio-composites. These materials can be easily modified by adding functional groups to provide colloidal stability in biological media, facilitating the delivery of molecules and promoting sustained release of biological agents.

Similarly to NCs, the application of quantum dots (QDs) represents another significant achievement via nanotechnology.

Gold NanoparticlesGold nanoparticles have recently been introduced in a variety of applications in cancer diagnosis and treatment. Several studies reported the synthesis of gold nanorods, nanocages, nanoshells, and nanospheres , generating promising compounds to be used as contrast agents,radiosensitizers, photothermal agents, and drug delivery nanocarriers.

The main benefits are their low cytotoxicity and wide variety of possible chemical functionalizations.

NanocompositesConsidering the variety of nano-based dental materials reported herein, nanocomposites and resin-based dental materials containing nanoparticles currently have the highest feasibility for clinical use. The use of nanoparticles allows the addition of larger amounts of fillers into dental resin composites compared to those containing microparticles . Although some of these dental materials are already commercialized, there are still concerns regarding the inhalation of released nanoparticles during abrasive procedures such as re-shaping, polishing,and removing fillings prepared with these nanocomposites

Application of Resin-BasedComposites (RBCS) Incorporatedwith Nanoparticles for DentalRestorations.

Resin-Based Composites Containing Nanoparticles and Nanoclusters

Resin composites have been refined during the past decade for use in both anterior and posterior regions of the oral cavity, mainly through the evolution towards nanocomposites. These resin-based composites (RBCs) containing nanoparticles exhibit a high surface free-energy that exerts differential behavior in terms of mechanical and physicochemical properties, such as an excellent color density, low polymerization shrinkage, adequate surface brightness, low surface roughness, resistance to fracture, and excellent adherence to dental tissues

Nanomaterials Conjugated in Cements and Metals

Minimally invasive and atraumatic restorative dentistry requires the use of therapeutic restorative materials.

To achieve this goal, calcium phosphate nanoparticles and fluorinated hydroxyapatite nanocrystals have been developed and tested as potential dental filling materials with therapeutic ability to prevent and/or combat dental caries

Biomodulation of Dental Tissues through Nanotechnology

Different types of dental materials are capable of creating nano-arranged structures. For example, the use of resin-bonding systems containing specific functional monomers can createself-assembling of bonding nano-layers with calcium/hydroxyapatite present at the resin–dentin interface . These nano-layers were found when using commercial adhesives, thereby demonstrating the suitability of such treatment.

Biomodulation in Dentistry.

Concluding Remarks and Future PerspectivesThere is no doubt that recent developments in nanomaterials and nanotechnology have improved and will further advance dentistry and oral health care in the near future. Nevertheless, great challenges involving ethics and safety regulations, as well as cost-effectiveness, need to be addressed and overcome before new nano-based dental materials are introduced in the market.One of the most stimulating perspectives for dental restorative nanomaterials is that nanotechnology can mimic the physicochemical-mechanical properties and the aesthetic properties of dentin and enamel (biomimetics)

To date, many types of dental materials have been generated through nanotechnology and are available for clinical application; in particular, resin composites and cements that can be used to replace missing tooth structures.

Studies on the production, characterization, and application of nanomaterials are evolving quickly in different areas of dentistry. However, there is a need to evaluate the behavior of these nanostructures in the oral cavity, taking into consideration factors such as pH, buffer capacity of saliva, contact with the mucosa, and spreading of the dental tissues, because most of toxicology for nanostructured materials in dentistry is restricted to in vitro studies (see Outstanding Questions). In addition, more clinical studies are required for long-term evaluation of existing nanomaterials to better understand their mechanisms of action.

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