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140]

Systematic Review

Clinical considerations of nanobiomaterials in endodontics:

A systematic review
Mohammed S. Alenazy, Hezekiah A Mosadomi1, Saad Al-Nazhan2, Mohammad Ramadan Rayyan3
Ministry of Health, King Khalid Hospital, Alkharj, 1Research Center, Riyadh Elm University, College of Dentistry, 2Department of Restorative Dental
Sciences, Riyadh Elm University, College of Dentistry, 3Consultant in Prosthetic, Riyadh Elm University, College of Dentistry, Riyadh, Saudi Arabia

Abstract Introduction: Clinical dentistry and primary oral care continue to experience significant improvements
in quality at different levels of dentistry. These changes and improvements are of great benefit to both
patients and clinicians because of significant achievements and advances in the physical, chemical, and
biological sciences. Nanotechnology and its varied products are eloquent examples of these revolutionary
trajectories in scientific discoveries and endeavors. Scientific revolution of nanotechnology has afforded
the dental profession with a wealth of novel nanobiomaterials, templates for dental tissues regeneration,
oral fluid nanodiagnostics, and the potential ability to use nanoparticles to replace lost dental hard tissues.
Materials and Methods: A  manual and systematic electronic search was conducted using the PubMed
database. Several keywords were used: “nanocharacterization” “nanoclinical applications” “endodontics”
“nanodentistry” “nanotechnology (263) (278) papers were excluded because they were duplicated papers,”
“nanoparticles” and “regeneration.” Relevant articles published up to 2016 in the English language were
retrieved.
Results: Initial electronic and manual searches identified (571) studies. Preliminary analysis was performed
on a total of (332) publication by screening titles and abstracts of articles. A second phase, data studies, or
unrelated reports were excluded. Full texts of the remaining (54) papers were retrieved. A manual search
added (6) publications on the topic to give a total of (60) publications, literature reviews, which were
included in this review.
Conclusions: Physical and chemical improvements in nanotechnology products continue to occur and may
soon lead to the development of “smart” endodontic therapeutic agents and materials. The future looks
auspicious for sustained dramatic inventions in novel nanomaterials for clinical dental applications.

Keywords: Endodontics, nanobiomaterials, nanotechnology, regeneration, sealer

Address for correspondence:  Dr. Mohammed S. Alenazy, Ministry of Health, King Khalid Hospital (Kharj), P.O. Box 21437, Riyadh 11475, Saudi Arabia.
E‑mail: alenazy.endodontics@gmail.com

INTRODUCTION imagine the varied applications of nanotechnology that

today pervade nearly all spheres of human activities. The
Over 60 years ago when the American Nobel Laureate concept, which evolved from Newton to Bernoulli, Dalton,
physicist Richard Feynman[1] conceptualized the potential Maxwell, Boltzmann, Rutherford and many other great
applications of “nanotechnology,” most likely he did not
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DOI: How to cite this article: Alenazy MS, Mosadomi HA, Al-Nazhan S, Rayyan MR.
10.4103/sej.sej_67_16 Clinical considerations of nanobiomaterials in endodontics: A systematic review.
Saudi Endod J 2018;8:163-9.

© 2018 Saudi Endodontic Journal | Published by Wolters Kluwer ‑ Medknow 163

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Alenazy, et al.: Nanobiomaterials in endodontics
minds, and the concept of atoms and molecules became
real and researchable. In the process, small measurements
in the order of angstrom, nanometers, and femtometers
became realities that could be applied to linear and
volumetric determinations.[2]
Nanotechnology and its products (i.e., applications) impact
our everyday lives today. It involves the development of
several materials and devices as well as systems exhibiting
properties different from those of larger scale.
Descriptive new terminologies within the general field of
nanotechnology have emerged: nanoparticles, nanowires,
nanotubes, nanoshells, nanospheres, nanocapsules
dendrimers, nanoassemblers, and many others. [2]
Nanoparticles are microscopic particles with dimensions
ranged from 1 to 100 nm. Between 2000 and 2014, over 60
published articles appeared in peer‑reviewed journals
describing the varied applications of nanotechnology and
its products in all areas of dental and oral care.
Robert Freitas has been credited with announcing the
new and emerging field of nanomedicine in 1993.[2]
Nanomedicine may be defined the diagnosis, treatment,
and prevention of diseases in health sciences with
nanosized particles in various forms. New words in disease
management have since entered drug usage, namely
“nanoscaffolds” for tissue regeneration and “nanorobotics”
for both diagnosis and therapy.[3] Dentistry, dental care, and
dental biomaterials are beneficiaries or products of what
may be called the “ocean” of nanotechnology that literally
manipulates molecules and atoms to create new products,
structures, and services.[4]
Despite the accumulation of knowledge of nanotechnology
in relation to dental materials, the application of
nanobiomaterials in endodontics needs to be highlighted.
This systematic review will focus on the possible application
of nanotechnology and nanobiomaterials in endodontics
scientific topics.
MATERIALS AND METHODS
A literature review was performed to determine the
potential uses of nanotechnology in endodontic treatments.
The review was conducted using the PubMed database,
a search engine mainly accessing the MEDLINE
database of references. Several keywords were used:
“nanocharacterization,” “nanoclinical applications,”
“endodontics,” “nanodentistry,” “nanotechnology,”
“nanoparticles,” and “regeneration.” Relevant articles
published up to 2016 in English language were retrieved.
164 Saudi Endodontic Journal | Volume 8 | Issue 3 | September-December 2018
RESULTS
A total of 571 studies were initially identified. A preliminary
total of 332 publications were included, and their titles
and abstracts were screened. During the second phase,
263 (278) were excluded because they were duplicated
papers, literature reviews, data studies, or unrelated
reports. The full texts of the remaining 54 papers were
retrieved. A manual search led to the discovery of six
additional publications on the topic to give a total of 60
publications [Figure 1]. The publications were categorized
according to the followings:
Nanotechnology in endodontics
Endodontic treatment over time has become a highly
predictable procedure, reported to have more than
96% success rates in the absence of preexisting apical
periodontitis.[5] Biomechanical steps, disinfection, and
three‑dimensional sealing and obturation of the root
canal system are essential procedures in the success of
endodontic treatment.[6] Despite the established high
success rate of root canal treatment, failure still occurs due
to the inadequacy of the biomechanical step of the complex
anatomical canal system and/or microleakage of the sealing
material. This microleakage most likely occurs because of
quality deficiencies.[7,8] Recent endodontic materials have
particular limitations of shrinkage, dissolution in oral
environment, and sensitivity to moisture.[9] Predictably,
Identification:
Electronic database sources: (n = 571)
Excluded studies (n = 239)
Screening:
Recorded after titled and abstract screened
then included (n = 332)
Excluded studied for duplicate paper,
literature reviews, data for
unrelated reports (n = 278)
Eligibility Include:
Electronics source full-text screened (n = 54)
Manual source full-text screened (n = 6)
Figure 1: Data flowchart
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Alenazy, et al.: Nanobiomaterials in endodontics

the development of suitable materials that have superior
biomechanical and sealing properties for root canal systems
is ensuring the longevity of endodontic treatment success.
A new era of nanomaterials studies has resulted in material
development that improves clinical outcomes. A simple
definition of nanotechnology is the “creation of functional
materials with structures sized, 100 nm, or smaller.”[10] The
field of endodontology has a considerable number of
ongoing research activities that are attempting to improve
several clinical management aspects such as files and
filling materials. Some nanoparticles possess antimicrobial
properties that might enhance the efficacy of endodontic
materials, irrigation solutions, and intracanal medicaments
because of their minute size and ability to spread into
complex anatomical areas in root canal systems[11,12] as
shown in Table 1.
The majority of efforts have continuously focused on
creating “nanomodified” materials. The spreading of these
particles in recent and novel materials could strengthen the
sealability of obturation and sealer materials, which are used
either in root‑repair and/or root‑end filling materials.[12,22]
Nanoapplications in endodontics instruments
Nickel‑titanium (NiTi) endodontic rotary files are one of
the most commonly used instruments in endodontic regular
daily dental practice. These types of alloys have numerous
favorable characteristics including high corrosion resistance
and superelasticity which endows them with excellent
shape memory. This type of rotary file makes it possible
to explore the complex anatomy of a root canal to ensure
appropriate endodontic treatment.[23,24]
Cobalt coatings of the NiTi file with impregnated
fullerene‑like WS2 nanoparticles cause a significant
improvement in the fatigue resistance and breakage time.
Nanoenhancement of the canal disinfection material
Various medical solutions are used for sterilizing root
canal spaces, and these solutions are generally categorized
as either irrigants or medicaments. Clinically, the usage
of irrigants is often conducted in a significantly higher
volume than medicaments. In addition, irrigants require
longer contact times inside canal walls, and medicaments
have to be applied over a longer period to achieve efficacy
at disinfecting the canal system. The incorporation
of nanoparticles has been proposed for irrigants and
medications to enhance their ability at sealing and
disinfecting the entire root canal system.
Endodontic canal irrigants
Eradication and disruption of microbial biofilms within the
root canal space are the objectives behind implementing the
biomechanical step. Despite emphasis being placed on the
mechanical instrumentation of root canals, irrigants have
been shown to play a key role in the disinfecting process
within the canal system.[25] This property of disinfection
is very important in complex canal anatomy systems
(e.g., fins and the isthmuses) that cannot be easily cleaned
or are easily missed by instrumentation alone.[26]
A fundamental concern with regard to irrigating fluids
and their techniques is the ability to reach all regions of
the canal spaces and remove debris such as the smear
layer and biofilms without causing harm to normal tissues.
Several types of irrigants and techniques are generally
used manually or mechanically when disinfecting a
root canal system. Recent reports have explored using
nanoparticle‑type irrigants to improve the cleaning of
root canal systems; these studies have also focused on
tissue responses to the use of such irrigants.[27] One of
the materials that had been used over the last decade
is silver nanoparticles. These nanoparticles have been
used in different applications as an antibacterial and
antifungal agent and as a component of biotechnology
and bioengineering in dental care.[10,28] A study using an
animal model reported that animal tissue tolerated a sponge
embedded with either 47 or 23 ppm sliver nanoparticles as
dispersion material filled in polyethylene tube better than
control animals tissue with a plain fibrin sponge embedded

Table 1: Numerous studies for different nanomaterial and their proposed application
Number Author Year Nano‑material Proposed application
1 Shrestha et al.[11] 2009 Antibacterial nanoparticles Irrigation and intracanal medicaments
2 Pagonis et al.[13] 2010 PLGA nanoparticles Irrigation
3 Gbureck et al.[14] 2007 Nanocrystalline tetracalcium phosphate cements Pulpcapping agents and endodontic sealers
4 Saghiri et al.[15] 2012 Nanomodification of mineral trioxide aggregate Pulpcapping agents and perforation repair material
5 Chogle et al.[16] 2011 Polymer nanocomposite Root‑end filling material
6 Modareszadeh et al.[17] 2011 Polymer nanocomposite Root‑end filling material
7 Fioretti et al.[18] 2011 PGA Endodontic regeneration
8 Yang et al.[19] 2010 Nanofibrous PCL/gelatin/NHA scaffolds Endodontic regeneration
9 Hu et al.[20] 2010 Nanofibrous PLLA scaffolds Endodontic regeneration
10 Gupta and Ma[21] 2012 Nanofibrous scaffolds Endodontic regeneration
PLGA: Polyacticcoglycolic acid, PGA: Polyglutamic acid, PCL: Polycaprolactone, PLLA: Poly‑L‑lactic acid, NHA: Nanohydroxyapatite

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Alenazy, et al.: Nanobiomaterials in endodontics
with 2.5% sodium hypochlorite over 3 months.[29] The
authors concluded that a 23 ppm concentration of silver
nanoparticle dispersion material was more biocompatible
with tissue compared with other materials. Then, a concern
about health issues was raised. After reviews of the
toxicological effects of exposure to silver nanoparticles,
it was reported that these nanoparticles might be linked
to several problems with “inflammatory, oxidative,
genotoxic, and cytotoxic consequences.”[30] Additional
clinical trials studies were justified to confirm the safe
utilization of these nanoparticles in both filed medical and
dental applications. An alternative method of disinfecting
root canal spaces, which is called nanoparticle‑based
antimicrobial photodynamic therapy, has been investigated
with promising preliminary findings. In an in vitro study
by Pagonis et al., the effectiveness of polyacticcoglycolic
acid (PLGA) nanoparticles synergized with light against
Enterococcus faecalis was assessed using transmission electron
microscopy and photosensitizer methylene blue (MB).[13]
These authors found that the nanoparticle component
acted generally on microorganism’s cell walls causing a
significant reduction in the number of colony‑forming
units in the culture. They concluded that the use of
PLGA nanoparticles encapsulated with protective drugs
might be a promising step in antimicrobial root canal
treatment. Another comparative study showed that the
cationic photosensitizer had the ability to deactivate the
content of microbial biofilm bacteria such as E. faecalis
and worked to disrupt the structure of biofilm.[31] These
nanoparticle‑based disinfections may become important
additions to the currently available conventional irrigants
used in endodontic treatment.
Root canal sealers
The sealer enhances the conceivable achievement of an
impervious seal and serves as filler for canal irregularities
and minor discrepancies between the root canal spaces
and the obturation material (e.g., gutta‑percha). Sealers
frequently get into accessory or lateral canals, and they
can help with microbial control in case that there are
microorganisms remaining in dentinal tubules.[32,33] Sealers
can likewise serve as lubricants to aid in the sealing
of the obturation core‑filling material in the thorough
compaction. Inside root canals where the smear layer has
been removed, numerous types of sealers exhibit expanded
adhesive features to dentin tubules.[34,35] Since the small size
of nanoparticles ensures that they can penetrate dentinal
tubules to seal all spaces effectively, the development of a
sealer based on nanotechnology may be an important step to
achieve a better sealer material in endodontics. Investigators
have studied nanohydroxyapatite (NHA) crystals (279 nm)
as the primary composition of new biotype root canal filling
166 Saudi Endodontic Journal | Volume 8 | Issue 3 | September-December 2018
sealers based on calcium phosphate cement on extracted
teeth.[36] This sealer exhibited stronger antimicrobial
properties against Actinomyces naeslundii, Porphyromonas
gingivalis, Porphyromonas endodontalis and Fusobacterium
nucleatum than regular sealers. In addition, it demonstrated
insignificant microleakage compared with different
materials. In another preliminary study, nanocrystalline
tetracalcium phosphate had essentially a higher antimicrobial
strength in an agar‑diffusion test.[14] The development of
amorphous calcium hydroxide during setting was thought
to increase the pH level in the agar gel around the
examples yielding a zone of restraint. Others materials,
available in the market‑containing nanosize particles,
include Mineral Trioxide Aggregate (MTA‑Fillapex), iRoot
SP, and EndoSequence BC root repair material. These
materials are biocompatible, antimicrobial, and possess
biomineralization.[22] In addition, they demonstrated a
moderate toxicity that diminished over the time when
completely set.[37]
Retrofilling and root‑repair materials
Various studies have described the importance of
retrograde root filling placement during periapical surgery
such as MTA and EndoSequence BC root repair materiel
putty. Wu et al.[38] recommended that a tight and durable
seal of retrograde root fillings is of essential clinical
importance. A few studies have shown that, in the absence
of an acceptable root canal filling, surgical treatment can
be compromised.[39] Moreover, various clinical studies
pertaining to healing quality after periradicular surgery
have affirmed the advantage of doing acceptable root canal
filling before surgery.[40] MTA has become the material of
choice for retrograde fillings despite its drawbacks of long
handling and setting times. To remove these drawbacks, a
recent study by Saghiri et  al.[15] assessed a nanomodified
MTA for upgraded physiochemical properties. They
found that there was an increase in the surface area of the
MTA powder with the addition of nanodispersion, which
decreased the setting time and enhanced the microhardness
of the material. This modification apparently aided the
MTA in setting faster but compromised the required
hardness once it was completely set. Other researchers
are investigating and exploring new materials as opposed
to adjusting current materials. The term polymer
nanocomposite (PNC) is generally used for all polymeric
materials that are loaded with a minimum amount
of nanoparticles such as clays and carbon nanotubes
compared with conventional composites.[41] The dispersed
phase has a high surface‑to‑volume proportion. PNCs have
therefore demonstrated significantly enhanced mechanical
and thermal properties, even at very low content of
fillers in the range of 0%–5%. The previous studies have
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Alenazy, et al.: Nanobiomaterials in endodontics
demonstrated considerable enhancements in resistance
to heat,[41] dimensional stability,[42] stiffness,[43] reduced
electrical conductivity[44] and most remarkably, drug elution
abilities.[45] Recently, two such novel nanocomposites
polymer (NERP1 and NERP2) were examined for initial
apical seal alongside a regularly used polymer‑based
compomer in an in vitro study model.[16] They found that
NERP1 can reduce apical microleakage significantly.
Modareszadeh et  al. assessed the bioactivity values and
cytotoxicity of two forms of novel root‑end filling
materials, PNC resins (C‑18 amine montmorillonite [MMT]
and vinylbenzyl‑octadecyldimethylammonium chloride
MMT) compared to ProRoot_ MTA and Geristore.
Their results demonstrated no significant difference in
cytotoxicity among ProRoots MTA, Geristores and PNC
resin C‑18 at all time intervals.[17]
Nanoapplications for repair and pulp regeneration
The primary concern of researchers and clinicians in
dental tissues studies is to achieve total recovery of dental
pulp tissues. In endodontology, repair and regeneration
are concerned with systems and mechanisms involved
in maintaining or restoring the original structures and
functions by manipulating the embryonic stem cell
development process. In the human body, there are several
low‑compliance systems, of which dental pulp is considered
to be an example due to its enclosure between rigid
encasement walls. An alterations in capillary filtration, such
as in inflammation, can have dramatic effects. Therefore,
it is difficult to access dental pulp without creating an
inflammatory reaction. From this point of view, probable
repair and/or regeneration of injured, inflamed or necrotic
dental pulp must be preceded by an understanding of the
nature of this action. An unusual attribute of dental pulp
is that it has completely sensory tissue. Human pulp has
several unusual features such as terminal microvascular
supplies, few anastomoses, and a generally large volume
of tissue with generally little vascular supply.[46] The types
of vessels that enter and exit pulp tissue are arterioles
and venules. Finally, the most likely significant obstacle
to repair and regeneration in responding to pulp stress
is that the pulp is enclosed by a hard tissues of dentin,
enamel (crown), and cementum (root).[47] However, despite
the surrounding environment of dental pulp, it possesses
a considerable ability to repair itself.
The principal cause of pulpal reactions to stresses is
the onset of dental caries. When it progress, pulpal
inflammatory reaction is elicited, and as it gets deeper
inside the enamel and dentin, the microorganism and
their toxic products reach directly into pulp tissue. When
the cause (caries) is removed at an early stage, the damage
Saudi Endodontic Journal | Volume 8 | Issue 3 | September-December 2018 167
and the inflammation of the pulpal tissue will normally be
resolved. Recently, investigations have shown that repair
and regeneration can occur in a low‑compliance system
such as dental pulp.[47] Several studies have been carried out
in animal models with dentition similar to humans.[48] The
ultimate aim of these studies has always been to grow a
natural tooth, including its soft and hard tissues, to replace
a missing tooth. The technology is now available for this
growth to be achieved in the not‑so‑distant future.
In recent studies, concern has been expressed about the
application of results from animal models to humans in
the area of tissue regeneration. The complexity of efforts
is related to the components of stem and progenitor cell
proliferation,[49] differentiation development,[50] scaffold
types,[51] the regeneration of neural and vascular tissues,[52]
and mechanisms of signaling and the proteins that are
involved in the process of signaling.[53]
An investigation was conducted to test the microleakage
of five bonding systems using nanoparticles of silver
ammoniacal nitrate. The findings were evaluated under
an SEM in emission environment in a backscattered
electron mode of an yttrium aluminum garnet laser.
Detection of the probable existence of silver particles
was conducted using an electron dispersive system analysis
in parallel. Three types of restorative systems indicated
clear silver uptake in the adhesive and hybrid layers.[54] A
recent study by Fioretti and his group tested the toxicity
of nanostructured assemblies on the dental pulp tissues.
Anti‑inflammatory properties were demonstrated through
alpha‑melanocyte‑stimulating hormone (MSH). The
combination of substances polyglutamic acid‑alpha‑MSH
decreased the amount of lipopolysaccharide caused the
proliferation of fibroblast cells. Although the mechanism
of action of this substance is not clear yet, it may
play an important regulatory function in modulating
pulpal inflammation.[18] Another study used caffeic acid
phenyl ester, which prevented the endogenous matrix
metalloproteinases that cause hybrid layer degradation.[55]
The completion of maturation all through the crown
and roots occurs through the continuous process of
mineralization.
An odontoblast is a nondividing cell that functions over the
lifetime of dental pulp. If it is succeeded by a cell, it is called
an odontoblast‑like cell in the case of infection or injury.
Secondary dentin forms due to physiological processes
during the lifetime of a tooth from activities of the
original odontoblastic layer by the same mechanism
that produced the primary dentin. Both primary and
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Alenazy, et al.: Nanobiomaterials in endodontics
secondary dentin have tubules.[56] Odontoblast‑like cells
are presumed to give rise to a form of a dentin‑like
structure.[57] Nanostructured polymer scaffolds had been
developed and examined by Smith et al. for regeneration
and bioengineering.[58] The investigation concentrated
on nanofibrous  (NF) scaffolds with combinations of
components. This material is composed of extracellular
matrices (ECM), the dimension of which range between
50 and 500 nm. A polymer with biodegradable properties
is then cast through the scaffold porosity to form NF
with nanofibers that have the same diameter as the
ECM. In NF and composite control scaffolds, the ability
of the cell to adhere, proliferate, and differentiate is
improved.[58]
The production of an engineered replica of the naturally
occurring ECM can promote new tissue development.
This achievement is a significant step forward in
understanding the improved biological regulation of
cell behavior for tissue repair and regeneration. [58]
One study has assessed the behavior of dental pulp
stem cells (DPSCs) on different scaffolds such as
NF/gelatin/nano‑hydroxyapatite NHA. A seeding
process of DPSCs was initiated on electrospun
poly/gelatin scaffolds either with or without NHA.
Different tests were conducted that analyzed the in vitro
DNA content, the movement of alkaline phosphatase,
and measurements of osteocalcin, which demonstrated
that the scaffolds supported the adhesion of DPSCs,
proliferation, and differentiation of odontoblasts. The
two types of scaffolds were seeded with DPSCs that were
embedded subcutaneously into immunocompromised
nude mice. The control group contained scaffolds with
NHA but without DPSCs. The results of the study
demonstrated that the combination of NHA on scaffolds
upregulated a specific expression of odontogenic
gene, and then, NHAs with nanofibers enhanced the
differentiation of DPSC to be odontoblast‑like cells
phenotypically in both in vitro and in vivo study models.[59]
One study assessed the differentiation of human
odontogenic DPSCs on NF poly L‑lactic acid (PLLA)
scaffolds.[60] Another study used highly permeable scaffolds
of NF‑PLLA that mimicked collagen type‑I fibers with and
without the usage of growth factors “Bone Morphogenic
Protein‑7 (BMP‑7)” and dexamethasone (DXM) medium.
The mixing of the growth factor BMP‑7 and DXM
stimulated the differentiation of odontogenic DPSCs
more effectively than DXM alone. Finally, the environment
that was provided by the nanoscaffolds was excellent
support for DPSCs in regenerating dental pulp, dentin,
and enamel.[21]
168 Saudi Endodontic Journal | Volume 8 | Issue 3 | September-December 2018
CONCLUSIONS
The cumulative literature data have indicated that the
importance of nanotechnology revolution on endodontics
practice is yet to be realized. Nanotechnology applications
are relevant to root canal therapy in several aspects, namely,
canal irrigation, instrumentation, obturation, canal sealers,
pulp repair, and/or endodontic regeneration therapy.
Physical and chemical improvements in nanotechnology
products continue to occur and may soon lead to the
development of “smart” endodontic therapeutic agents
and materials. The future looks very promising for dramatic
nanoenhancement in inventing novel materials in all aspects.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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