Nanotechnology has enabled the development of innovative and cost-effective dental materials and devices. The document discusses various nanomaterials that have antimicrobial properties for use in dental applications, including silver nanoparticles, zinc oxide nanoparticles, titanium dioxide nanoparticles, and chitosan nanoparticles. Polymeric nanoparticles, gold nanoparticles, carbon nanotubes, and quantum dots show promise for therapeutic applications such as drug delivery. Resin-based dental composites containing nanoparticles demonstrate improved mechanical and optical properties compared to microparticle composites. While nanotechnology has advanced dentistry, further research is still needed to fully evaluate the safety and efficacy of nanomaterials in clinical dental applications.

1. Advances in Dental Materials

2. Nanodentistry
NANOTECHNOLOGY 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

3. 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).

4. Antimicrobial Dental Nanomaterials
SILVER NANOPARTICLES (AGNPS)
ZINC OXIDE-BASED NANOPARTICLES (ZNONPS)
TITANIUM DIOXIDE-BASED NANOPARTICLES (TIO2NPS)
COPPER-BASED NANOPARTICLES (CUNPS)
CHITOSAN NANOPARTICLES
NANOMATERIALS AND QUATERNARY AMMONIUM COMPOUNDS (QACS)

5. 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

6. Silver Nanoparticle (AgNPs)
Activity against Bacteria

7. 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

10. Zinc Oxide-Based Nanoparticles (ZnONPs)
Zinc has been also used in dentistry for many years as the major
filler 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

13. 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 .

15. 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.

17. Chitosan Nanoparticles
Chitosan, 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 flow 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

19. 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 and
Lactobacillus 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

21. Nanomaterials for Therapeutic Dentistry
• Polymeric Nanoparticles
• Carbon Nanomaterials and Quantum Dots
• Gold Nanoparticles

22. Polymeric Nanoparticles
Nanoparticles 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, facilitating
diffusion 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 .

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

24. Carbon Nanomaterials and Quantum Dots
Nanocarbon 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.

25. Gold Nanoparticles
Gold 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 .

26. Nanocomposites
Considering 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

27. Application of Resin-Based
Composites (RBCS) Incorporated
with Nanoparticles for Dental
Restorations.

28. 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

29. 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

30. 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 create
self-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 .

31. Biomodulation in Dentistry.

32. Concluding Remarks and Future Perspectives
There 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)

33. 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.

34. 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.

35. The end