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Nanotechnology and its role inthe management of periodontaldiseases
LING XUE KONG, ZHENG PENG, SI-DONG LI & P. MARK BARTOLD
With the unstoppable trend of an increasing aging
population in both the developing and developed
countries, scientists in the field of regenerative
medicine and tissue engineering are continually
looking for new ways to apply the principles of cell
transplantation, materials science, and bioengineer-
ing to construct biological substitutes that will restore
and maintain normal function in diseased and
injured tissues (2). In addition, the development of
more refined means of delivering medications at
therapeutic levels to specific sites is an important
clinical issue. Applications of such technology in
dentistry, and periodontics in particular, are no
exception as periodontal destruction can be found to
increase in prevalence with increasing age (42, 52).
The traditional clinical procedures of scaling, root
planning and periodontal flap surgery, if followed by
an adequate postoperative supportive periodontal
care, results, in most cases, in successful manage-
ment of progressive periodontal diseases (27, 62, 65).
More recently, the regenerative treatment of perio-
dontal defects with an agent, or procedure, has
attracted enormous interest from materials scientists
and also from both private companies and govern-
ment organizations because of its considerable eco-
nomic potential (4, 43) and scientific significance.
One of the emerging areas is tissue engineering that
seeks to develop techniques andmaterials to aid in the
formation of new tissues to replace damaged tissues
(4). Guided tissue engineering has been successfully
used in the treatment intrabony defects (14) and fur-
cation defects (45, 65). A more general review of tissue
engineering concepts in terms of periodontal regen-
eration has been carried out by Bartold et al. (4).
The necessary strategies for complete regeneration
of human tissues should be the ultimate endpoint for
the field of regenerative medicine and engineering.
However, for many tissues this goal remains elusive
(74). Nonetheless, there has been significant progress
made in recent years with the development and
introduction of various metallic and polymeric
materials structured in nanoscales (17, 46, 75, 84) and
the development of many biomaterials that form
ideal interfaces with tissues (7, 84). Using natural
processes as a guide, substantial advances have been
made at the interface of nanomaterials and biology,
including the fabrication of nanofiber materials for
three-dimensional cell culture and tissue engineering
(84). One example of such applications in the man-
agement of periodontal diseases is the evaluation of
two typical cellular components of a hard ⁄ soft tissueinterface such as the periodontal ligament ⁄ mandible
and patellar tendon ⁄ tibia (7). Tissue engineering of
such complex interfaces requires a contiguous scaf-
fold system with at least two cell types associated
with the engineering of both hard and soft connective
tissues.
In the pharmaceutical domain, liposomes and
polymer-based micro- and nanoparticles are the
subject of current intense research and development
(72). In addition, metallic particles, which were first
introduced in the first half of the 1980s, are now
experiencing a renaissance. A very new generation of
biosensors based on the optical properties of col-
loidal gold nanocrystals and nanoparticles is ready
to be implemented in diagnosis and medical ima-
ging (72) as well as tagging DNA sandwich assays
(19, 57). Concerning therapeutic applications, the
potential of metallic and polymeric nanoparticles to
help fulfill the need for timely and accurate con-
trolled release of drugs can be explored by syn-
thesizing materials of tailor-designed structures,
such as hybrid hollow spheres (9) and core-shell
structures (11).
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Periodontology 2000, Vol. 40, 2006, 184–196
Printed in the UK. All rights reserved
Copyright � Blackwell Munksgaard 2006
PERIODONTOLOGY 2000
From the definition provided by the National
Nanotechnology Initiative, nanotechnology exploits
specific phenomena and direct manipulation of
materials on the nanoscale (28). However, nano-
technology is much more than the study of small
things; it is the research and development of mate-
rials, devices, and systems exhibiting physical,
chemical, and biological properties that are different
from those found on a larger scale. Thus nanotech-
nology can be best understood as a broad collection
of technologies – from diverse fields such as physics,
materials science, engineering, chemistry, biochem-
istry, medicine, and optics – each of which may have
different characteristics and applications. Therefore,
it is not the intention of this review to cover the
development of nanotechnology in all areas and its
impact on periodontal diseases. Rather, it will focus
on the development of nanomaterials and their
potential to be used in managing periodontal dis-
eases, including diagnosis and treatment.
Nanomaterials and self-assembly
Nanomaterials are those materials with components
less than 100 nm in at least one dimension, including
clusters of atoms, grains less than 100 nm in size,
fibers that are less than 100 nm diameter, films less
than 100 nm in thickness, nanoholes, and compos-
ites that are a combination of these. The composition
can be any combination of naturally occurring ele-
ments.
Because nanoparticles have significant surface
effects, size effects, and quantum effects,
nanocomposites usually exhibit much better per-
formance properties than traditional materials. The
improved relevant properties include enhanced
toughness, stiffness, improved transparency, in-
creased scratch, abrasion, solvent and heat resist-
ance, and decreased gas permeability. In addition,
nanoparticles have special properties, including
chemical, optical, magnetic, and electro-optical
properties, which differ from those of either indi-
vidual molecules or bulk species. These significant
properties of nanoparticles meet the intriguing
demand to design multifunctional nanocomposite
films, which cover properties of both inorganic and
organic materials and exhibit immense prospects
for developing light-emitting diodes, nonlinear op-
tical devices, resistors, sensors, electrically conduc-
tive films, and gas separation membranes.
Inorganic nanoparticles either currently in use or
under development include semiconductor
nanoparticles (24), metal nanoparticles (22), metal
oxide nanoparticles (10), silica nanoparticles (21),
polyoxometalates (30) and gold nanocrystals (19).
Another important feature of nanostructured
materials is the development of self-assembly. Here,
an autonomous organization of components into
patterns or structures without human intervention
occurs (80). The whole process can be manipulated
and facilitated through the correct setting of condi-
tions (3, 58). Importantly, in the context of self-
assembly of nanostructures there is the simple
concept that cells and tissues self-assemble, and thus
understanding life will require an understanding of
self-assembly. Cells and tissues also offer countless
examples of functional self-assembly that stimulate
the design of nonliving systems. Indeed, self-assem-
bly is one of the few practical strategies for making
ensembles of nanostructures and is therefore the
essential part of nanotechnology. Self-assembly is
common to many dynamics, multicomponents sys-
tems, from smart materials and self-healing struc-
tures to netted sensors and computer networks.
Self-assembly has been classified into static and
dynamic processes based on whether the system
dissipates energy (80). In static self-assembly, for-
mation of ordered structure requires energy but it is
stable once it is formed.
When choosing a material for self-assembly, the
materials should have a critical number of charged
groups, below which the assembling procedure does
not work at all. To form a well-defined stable multi-
layer, the appropriate opposite charge density is
required for the matched materials. To facilitate
analytical studies, the materials should bear some
functional groups, which can be detected by analyt-
ical instruments.
Polyelectrolyte materials bearing a number of
charged groups are most commonly used in self-
assembly as they enable stable, smooth, homogeneous
films to be formedwith anumber of functional groups.
The most widely used polyelectrolytes to date are
commercially available polymers. The cationic poly-
electrolytes include poly(ethyleneimine), poly(all-
ylamine), poly(diallyldimethylammonium chloride),
poly(allylamine hydrochloride), and diazo-resin. The
anionic polyelectrolytes are poly(styrene sulfonate),
poly(vinylsulfate) and poly(acrylic acid). Of these, the
best studied systems are poly(allylamine) ⁄ poly(sty-rene sulfonate) and diazo resin ⁄ poly(styrene sulfo-
nate) (6). Other polymers of current interest include
polyaniline, poly(vinyl pyrrolidone), poly(vinyl alco-
hol) (55, 56), poly(acrylamide), and poly(ethylene
oxide) (73).
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Nanotechnology and periodontics
The most universal driving forces for establishing
self-assembly are electrostatic attractive interactions
between positive and negative charges. Other inter-
actions such as hydrophobic interactions (37, 81),
charge transfer interactions (69), H-bonding, coordi-
nation bonding (32) and covalent bonding are also
emerging as important forces to be harnessed for
self-assembly purposes.
Self assembly of extracellularmatrices
The regeneration of hard and soft tissues around a
solid implant, or development of new tissues to
replace implanted biodegradable materials, will pro-
vide new vistas in the field of tissue regeneration. At
present, one of the major challenges in this field is to
integrate different functions into synthetic extracel-
lular matrices. Such matrices will ideally behave as a
mechanically sound adhesive, allowing immediate
fixation of the implant before cell-mediated proces-
ses take over the tissue regeneration processes (4, 74).
Most importantly, the synthetic extracellular matrix
will need to perform functions such as to sustain cell
viability and proliferation, allow the establishment of
a blood vessel network formation and provide suffi-
cient support to prevent tissue collapse (74).
It has been demonstrated that well organized self-
assembled nanostructures can be fabricated (44, 54,
76, 80). Within this class of structures are three dif-
ferent classes of block copolymer type architectures –
coil–coil diblock copolymers, rod–coil diblock co-
polymers, and rod–coil diblock oligomers (35). An
example of such a nanostructure is shown in Fig. 1
(76) in which the synthetic structure, analogous to
folded proteins in the definition of chemical sectors,
shape and topography, builds blocks for materials
that pack in ways that fill the space efficiently. It is
noticed (76) that flat objects such as two-dimensional
polymers are likely to form layered structures,
tubules and rods align uniaxially, and identically
shaped and sized nanostructures such as the paral-
lelepipeds are likely to tile into a wide variety of
superlattices (Fig. 1). Three-dimensional packing can
also been easily predicted and fabricated if simple
geometrical shapes such as flat objects, rods, and
tubules are used.
In recent times, developments in this field have
seen the use of pH-induced self-assembly of a pep-
tide-amphiphile to artificially construct a nano-
structured fibrous scaffold with the structural
features of extracellular matrix. Furthermore, after
cross-linking, the newly produced fibers are able to
direct mineralization of hydroxyapatite to form a
composite material in which the crystallographic
axes of hydroxyapatite are aligned with the long axes
of the fibers. This alignment appears to be the same
as that observed in vivo between collagen fibrils and
hydroxyapatite crystals in bone (25). Other develop-
ments have included the synthesis and characteri-
zation of a series of self-assembling biomaterials with
molecular features designed to interact with cells and
scaffolds for tissue regeneration (29).
Nanomaterials with sphericalnanoparticles
The prospect of a new generation of materials based
on the assembly of nanoparticles into spatially
extended two- and three-dimensional arrangements
is a major driving force in the rapidly emerging field
of nanomaterial research (20). Nanoparticles, the
�designer molecules� which govern the macroscopic
behavior of these novel materials, can be constructed
according to a vast range of design principles,
promising unprecedented tuning of material prop-
erties (33). Uniformly distributing inorganic nano-
particles into polymer matrices without aggregation
is one of the most important criteria in preparing
polymeric ⁄ inorganic nanocomposites (PINs).
Decher (16) introduced a method that allows the
construction of multilayer assemblies based on layer-
by-layer adsorption. Different from the buildup of
such multilayers on macroscopically flat substrates,
Caruso et al. (9) developed a novel way for the pro-
duction of core-shell materials of given size, topol-
ogy, and composition (Fig. 2) and subsequent
removal of the core by either dissolution to produce
hollow particles or decomposition to give hollow
polymer shells.
The fabrication of hollow inorganic silica and
inorganic-hybrid spheres can be achieved through
the colloid templated electrostatic layer-by-layer self-
assembly of silica nanoparticle (SiO2)–polymer
multilayers, followed by the removal of the templated
core and, optionally, the polymer (Fig. 2). Polystyrene
latex particles of 640 nm in diameter have been used
as templates, and SiO2 particles of approximately
25 nm in diameter used as the coating nanoparticles.
These nanoparticles electrostatically self-assemble
onto the linear cationic polymer poly(diallyldi-
methylammonium chloride) (PDADMAC) (16). The
186
Kong et al.
wall thickness of the hollow spheres and ultimately
their shape and stability are dependent on the
number of SiO2-PDADMAC layer deposition cycles
(Fig. 2, steps 2 and 3).
It has been demonstrated that the layer-by-layer
self-assembly technique, when applied to produce
composite SiO2 nanoparticle-polymer multilayers on
colloids, coupled with removal of the core (and
optionally the polymer), provides a successful path-
way for fabricating inorganic and inorganic-hybrid
hollow spheres in the submicrometer-to-micrometer
size range.
There are a number of important advantages to
using this method to fabricate hollow spheres. Firstly,
the thickness of the hollow sphere walls can be
readily controlled by varying the number of depos-
ition cycles. Secondly, the size and shape of the
spheres produced are determined by the dimensions
of the templating colloid employed. Thirdly, the
method is generally applicable to a wide variety of
charged inorganic particles, thereby making possible
the production of various inorganic (such as TiO2 and
ZrO2) and composite (magnetic nanoparticle and
SiO2 or TiO2) hollow spheres.
Polymeradsorption (2) SiO2
(1) (3) PDADMACColloidalparticle (2), (3) …
Calcination Exposure toSolvent
HollowInorganic-Hybrid Spheres
Multilayer-CoatedParticles
Hollow Silica Sphere
Fig. 2. Illustration of procedures for preparing inorganic and hybrid hollow spheres. The scheme is shown for polystyrene
latex particles. PDADMAC, poly (diallyldimethylammonium chloride). (Reprinted with permission from Caruso et al.
Science 1998: 282: 1111–1114 (9); copyright (1998) AAAS).
Fig. 1. Supermolecular nanostruc-
tures with well defined shapes and
sizes. (Reprinted with permission
from Stupp et al. Science 1997: 276:
384–389 (76); copyright (1997)
AAAS).
187
Nanotechnology and periodontics
Core-shell nanostructures
Core-shell particles have attracted much research
attention in recent years because of the great
potential for protection, modification, and functional
properties of the core particles with suitable shell
materials to achieve specific physical (optical,
mechanic, and magnetic), chemical (reaction activity
and catalytic), and biological performance (curing,
drug delivery and release) (11, 67). Core-shell parti-
cles possessing complete and smooth shells can be
prepared with various technologies, for example, by
introducing nanoparticles of desired shell material,
prepared with the reverse micelle process, onto the
core particle surface via layer-by-layer electrostatic
adsorption, hydrophilic and hydrophobic interac-
tions, and subsequent sintering (11).
There are many advantages to such a synthetic
approach (67). The confined cubic micrometer or
submicrometer volume enables one to carry out
chemical synthesis in a highly organized solvent
structure, which can result in new composite nano-
materials that are impossible or difficult to synthesize
in conventional bulk media. This process also allows
the in situ fabrication of nanoreactors filled with
catalytically active components, and it also dimin-
ishes the effect of overconcentration and overheating
in the reaction vessel when reagents are added.
Through such processes it is possible to tailor dif-
ferent functionalities to the microenvironments as a
result of synthesis in one action, thus permiting
modeling and mimicking of biochemical processes in
living cells and their compartments by means of
nanoscale chemistry.
A biomimetic synthesis of the most typical apatite –
calcium hydroxyapatite, Ca10(PO4)6(OH)2 – exclu-
sively inside polyallylamine hydrochloride ⁄ poly(styrene sulfonate) (PSS) polyelectrolyte capsules has
been described and illustrated in Fig. 3a (68). The
thickness and particle size of the YF3 layer formed by
adding F– loaded capsules to a water solution con-
taining Y3+ ions depends greatly on the concentration
of yttrium salt in solution. For example, a 50–100 nm
layer made up from 7–10 nm particles is observed for
high Y3+ concentration, whereas separate agglomer-
ates attached to the inner wall are formed at low Y3+
concentrations (< 10)6 M). It has been reported that
the mechanical stability of such composite structures
is higher than that noted for the initial polyelectrolyte
structures (67).
Shchukin et al. also reported a method (Fig. 3b)
(66) in which entrapped PSS or polyaniline in emer-
aldine, form molecules which act as electron donors
for photoinduced silver reduction both inside and
(a)
Mn+ MAn
(Y3+,Ca2+)
Men+
(F-, PO43-)
An-
PAH/cit An-
CBA
(b)
El. Donor (PSS, dextran, polyaniline) UV/vis
(TiO3)
AgNO3
(Cu2+, Pd2+)
A CB
Fig. 3. Schematic of (a) the ion exchange nanosynthesis inside polyelectrolyte capsule (68); (b) photoinduced synthetic
reactions inside polyelectrolyte capsule (66). PAH, polyallylamine hydrochloride; PSS, polystyrenesulfonate.
188
Kong et al.
outside the capsule shell. It is envisaged that the
nanomaterials synthesized inside the confined cubic
micrometer and the submicrometer volume have a
number of advantages including:
• a high catalytic activity due to the nanoparticle
morphology and large surface area;
• a high stability of nanoparticles against aggrega-
tion;
• a microreactor shell that protects the nanomate-
rials from impurities;
• the formation of metastable and amorphous
modification;
• the possibility to carry out multistep synthesis
and to obtain composite, hierarchically architec-
tured nanomaterials (67).
Polyvinylalcohol ⁄ silicacomposites
The layer-by-layer self-assembly method as des-
cribed by Decher (16) has been applied to poly-
vinylalcohol ⁄ silica (PVA ⁄ SiO2), the result being a
novel nanocomposite (55, 56). The schematic repre-
sentation of this self-assembly monolayer nanocom-
posite process is shown in Fig. 4 (56). Firstly, the SiO2
nanoparticles are negatively charged and these act as
templates to adsorb positively charged polyallylam-
ine hydrochloride molecular chains through electro-
static adsorptive interaction. Polyvinylalcohol
molecular chains are then assembled on the surface
of SiO2 nanoparticles through hydrogen bonding
between the hydroxy groups of the polyvinylalcohol
and amino groups of the polyallylamine hydrochlo-
ride. Finally, the treated SiO2 nanoparticles are uni-
formly dispersed in bulk polyvinylalcohol matrix,
which is cast in a polytetrafluorethylene Petri dish,
and dried in a vacuum oven to obtain polyvinylal-
cohol ⁄ SiO2 nanocomposite film.
The SiO2 nanoparticles are found to be homogen-
eously distributed throughout the polyvinylalcohol
matrices as nanoclusters with an average diameter
ranging from 15 nm to 240 nm depending on the
SiO2 contents. The SiO2 nanoparticles are not
assembled in the composite as individual particles
but as clusters of particles. The number of nanopar-
ticles in a cluster depends on the amount of SiO2
added. As the average diameter of the SiO2
nanoparticles employed is just 14 nm, a complete
polyallylamine hydrochloride or polyvinylalcohol
molecular chain is longer than the circumference of a
single particle and is able to assemble more than one
Fig. 4. The schematic of PVA ⁄ SiO2 nanocomposite process (55, 56). PAH: polyallylamine hydrochloride; PVA: poly-
vinylalcohol.
189
Nanotechnology and periodontics
SiO2 nanoparticle. The average size is less than 30 nm
when the SiO2 content is below 5 wt%, indicating
that a SiO2 cluster has only (quite a few) primary
nanoparticles. However, at SiO2 contents of 10 wt%
and 15 wt%, the size of the SiO2 clusters is 100 nm
and 240 nm, respectively, which suggests that when
the SiO2 content is higher than a certain level,
nanoparticles will aggregate.
The nonisothermal crystallization behavior and
kinetics of the PVA ⁄ SiO2 nanocomposites have been
investigated and compared to those of pure polyvi-
nylalcohol (55). The degree of crystallinity (Xc), peak
crystallization temperature (Tp), half time of crystal-
lization (t1 ⁄ 2), and Ozawa exponent (m) on depends
heavily on the SiO2 content and cooling rate. The
crystallization activation energy (E), calculated with
the Kissinger model, is markedly lower when a small
amount of SiO2 is added. This then gradually
increases and finally becomes higher than that of the
pure polyvinylalcohol when there is more than 10
wt% SiO2 in the composite.
The mechanical properties of the polyvinylalco-
hol ⁄ SiO2 composite has also been improved signifi-
cantly over those of pure polyvinylalcohol (Fig. 5).
Polyvinylalcohol, as a plastic, shows a typical curve
having a yield point at 3.4% strain with a peak stress
of 65.7 MPa. A change of the fracture mechanisms is
observed, from the ductile fracture with a yield point
for composites with low SiO2 (0.5–5 wt%) to the
brittle fracture without yielding for high SiO2 com-
posites (10 wt% and 15 wt%). When 15 wt% SiO2 is
added into polyvinylalcohol matrix, the composite
becomes very brittle.
Dental tissues and nanostructures
Although tooth enamel, cementum, and bone are
composed of organized assemblies of carbonated
apatite crystals, enamel is unusual in that it does not
contain collagen and does not remodel. Self-assem-
bly of amelogenin protein into nanospheres has been
recognized as a key factor in controlling the oriented
and elongated growth of carbonated apatite crystals
during dental enamel biomineralization. Du et al.
reported (18) the in vitro formation of birefringent
microribbon structures that were generated through
the supramolecular assembly of amelogenin nano-
spheres. These microribbons have diffraction pat-
terns that indicate a periodic structure of crystalline
units along the long axis. The growth of apatite
crystals oriented along the c axis and parallel to the
long axes of the microribbons was observed in vitro.
The linear arrays (chains) of nanospheres observed as
intermediate states before the microribbon formation
give an important indication as to the function of
amelogenin in controlling the oriented growth of
apatite crystals during enamel mineralization. Whe-
ther similar processes involving supramolecular
assembly of nanostructures might be involved in
other mineralized tissues such as bone or cementum
remains to be established.
0
50
100
150
200
0 5 10 15 20 25
Strain (%)
rtS
ess
aP
M()
PVA
N-0.5
N-2
N-5
N-10
N-15
Fig. 5. Strain–stress relationship
of PVA and PVA ⁄ SiO2 nanocom-
posites. PVA, polyvinylalcohol.
190
Kong et al.
Direct visualization by transmission electron
microscopy, scanning electron microscopy, and
atomic force microscopy of microribbon, developed
by Du et al. (18), revealed that the larger aggregates
were the result of further association of nanospheres
in a linear arrangement (Fig. 6). Those subunits inside
a nanosphere had a quasispherical appearance, 4–
8 nm in diameter, consistent with the dynamic light
scattering measurement of amelogenin oligomers.
The bridging between nanospheres was observed by
thin threads (white arrow in the inset), the width of
which was on the same scale as that of the subunits.
The fusion of adjacent nanospheres is manifested as a
sharing of subunits (black arrow in the inset). The
linear alignment of several subunits was evident in-
side some nanospheres (upper inset). The further
association of nanospheres led to higher levels of
hierarchical structures. Nanosphere chains were also
observed by transmission electron microscopy as an
intermediate state before the formation of microrib-
bons (Fig. 6A). The nanochain structures were also
observed in the microribbons by atomic force micr-
oscopy (Fig. 6B.C). The size range of the nanospheres
(10–20 nm in diameter) in the microribbon was
consistent with the lower limit from dynamic light
scattering measurement in solution. Nanochains
more than 100 nm long were aligned roughly parallel
to the long axis of the ribbons (Fig. 6C).
Nanorods/nanofibers/nanotubesas dental materials
Nanoparticles are being developed for a host of bio-
medical and biotechnological applications including
drug delivery, enzyme immobilization and DNA
transfection. Spherical nanoparticles are typically
used for such applications as discussed above, but
this only reflects the fact that spheres are easier to
make than other shapes (36). Nanofibers that are less
than 100 nm in diameter, including nanorods (13, 23,
54), nanoplatelets, nanotubes (15, 57, 84), nanofibrils,
and quantum wires, are other major nanomaterials
being widely explored for various applications, of
which management of the periodontal diseases could
be a prime target.
Nanorods
The application of surfactants as reverse micelles or
microemulsions for the synthesis and self-assembly
of nanoscale structures is one of the most widely
adopted methods in nanotechnology. Chen et al. (13)
took advantage of these latest developments in the
area of nanotechnology to mimick the natural bio-
mineralization process to create the hardest tissue in
the human body, dental enamel, by using highly
organized microarchitectural units of nanorod-like
calcium hydroxyapatite crystals arranged roughly
parallel to each other. As detailed above, fully devel-
oped mature dental enamel is made of enamel
prisms, highly organized microarchitectural units,
which consist of bundles of nanorod-like calcium
hydroxyapatite crystals arranged roughly parallel to
each other. This structure spans the entire enamel
thickness and is likely to play an important role in
determining the unique physicochemical properties
of the enamel (12, 13).
Nanotubes
Kolhi & Martin (36) indicated that micro- and nano-
tube structures that resemble tiny drinking straws are
alternatives and may offer advantages over spherical
nanoparticles for some applications. Examples of
nanotubes include organosilicon polymer nanotubes,
self-assembling lipid microtubes, fullerene carbon
nanotubes, template-synthesized nanotubes, and
peptide nanotubes. They offer some interesting
advantages relative to spherical nanoparticles for
biotechnological applications (36). For example, the
large inner volumes (relative to the dimensions of
the tube) can be filled with any desired chemical or
biochemical species ranging in size from proteins to
small molecules (40). In addition, the distinct inner
and outer surfaces can be differentially functionalized
chemically or biochemically (47). The open mouths
may also make the inner surface accessible and make
incorporation of species within the tubes particularly
easy.
Many different approaches to making micro- and
nanotubes have been used and include:
• molecular self-assembly (8) by accurate and
controlled application of intermolecular forces;
• template-synthesized nanotubes – a general
approach for preparing nanomaterials that entails
synthesis or deposition of the desired material
within the cylindrical and monodisperse pores of
a nanopore membrane or other solids;
• in-pore polymerization to make polymeric nano-
tubes;
• electroless deposition to make metal nanotubes;
• sol-gel chemistry to make nanotubes composed
of silica and other inorganic materials.
191
Nanotechnology and periodontics
Fig. 6. Imaging of subunits and linear chains of nano-
spheres formed during amelogenin supramolecular
assembly. A) Transmission electron micrographs of the
linear arrays of amelogenin nanospheres collected. B)
Atomic force microscopy phase image of the surface of an
amelogenin ribbon. C) Back-transform with the frequen-
cies within the box in (B). (Reprinted with permission
from Du et al. Science 2005: 307: 1450–1454 (18); copy-
right (2005) AAAS).
192
Kong et al.
TiO2 nanotube arrays and associated nanostruc-
tures have recently been developed (50). Although
developed as a photocatalyst and for other sensor
applications, these structures may also be useful as
an incorporated nanostructure to titanium implant
metals for orthopaedic and dental implants. Vertic-
ally aligned nanotube arrays of titanium oxide can be
fabricated on the surface of titanium substrates by
anodization. During in vitro immersion in a simula-
ted body fluid, the nanoscale sodium titanate can
induce nucleation and growth of nano-dimensioned
hydroxyapatite. The kinetics of hydroxyapatite for-
mation appears to be significantly accelerated by the
presence of such nanostructures (50).
Nanomaterials for periodontal drugdelivery
Nanomaterials are of interest from a fundamental
point of view because the properties of a material
(e.g. melting point, electronic properties, optical
properties) change when the size of the particles that
make up the material becomes nanoscopic. With new
properties, come new opportunities for technological
and commercial development, and applications of
nanoparticles have been demonstrated or proposed
in areas as diverse as microelectronics, coatings
and paints, and biotechnology (36). From these
applications has come the development of nano-
pharmaceuticals, nanosensors, nanoswitches, and
nanodelivery systems. Each of these has considerable
significance in the field of local, or targeted, drug
delivery.
Recently, Pinon-Segundo et al. (59) produced and
characterized triclosan-loaded nanoparticles by the
emulsification–diffusion process, in an attempt to
obtain a novel delivery system adequate for the
treatment of periodontal disease. The nanoparticles
were prepared using poly(D,L-lactide-coglycolide),
poly(D,L-lactide) and cellulose acetate phthalate.
Poly(vinyl alcohol) was used as stabilizer. Batches
were prepared with different amounts of triclosan in
order to evaluate the influence of the drug on nano-
particle properties. Solid nanoparticles of less than
500 nm in diameter were obtained. These triclosan-
nanoparticles behave as a homogeneous polymer
matrix-type delivery system, with the drug (triclosan)
molecularly dispersed. Release kinetics indicates that
the depletion zone moves to the center of the device
as the drug is released. This behavior suggests that
the diffusion is the controlling factor of the release.
A preliminary in vivo study using these nanopar-
ticles has been performed in dogs with only the gin-
gival index (GI) and bleeding on probing (bleeding on
probing) being determined (59). With respect to the
gingival index (GI), at days 1 and 8, it was found that
a severe inflammation was detected in control and
experimental sites (GI ¼ 3). It was concluded that
triclosan nanoparticles were able to effect a reduction
of the inflammation of the experimental sites.
This study has specifically tackled periodontal
management; however, nanomaterials including
hollow spheres (9), core-shell structure (67), nano-
tubes and nanocomposite (55) have been widely
explored for controlled drug release (36, 38, 41, 49,
70, 78, 79). It is conceivable that all of these
materials could be developed for periodontal drug
delivery devices in the future. Drugs can be incor-
porated into nanospheres composed of a biode-
gradable polymer, and this allows for timed release
of the drug as the nanospheres degrade (39, 77).
This also allows for site-specific drug delivery.
A good example of how this technology might
be developed is the recent development of Arestin�
in which tetracycline is incorporated into micro-
spheres for drug delivery by local means to a
periodontal pocket (53).
Nanomaterials for periodontal tissueengineering
Currently, tissue engineering concepts for perio-
dontal regeneration are focused on the utilization
of synthetic scaffolds for cell delivery purposes (4).
Although the utilization of such systems offers
promise, it is very likely that the next generation of
materials will rely heavily on nanotechnology and
its potential to produce nonbiologic self-assembling
systems for tissue engineering purposes (5). As
detailed above, self-assembling systems for biologic
systems are those which automatically undergo
prespecified assemblies much in line with known
biologic systems associated with cells and tissues.
Using these principles, it is possible to construct
systems on a nano-, micro- or even macro-scale.
Current materials available for such constructs are
metals, ceramics, polymers, and even composite
materials, the like of which have not yet been
developed. The clinical utility of these nano-con-
structed self-assembling materials is their capacity
to be developed into nanodomains or nanophases,
leading to unique nanobuilding blocks with inbuilt
nanocontrol and nanodelivery capabilities. For tis-
sue engineering purposes the potential of nano-
technology is limited only by our imagination. Our
present capacity to create polymer scaffolds for cell
193
Nanotechnology and periodontics
seeding, growth factor delivery and tissue engin-
eering purposes is well recognized. In the future
these processes may well be manipulated via
nanodevices implanted to sites of tissue damage.
Concluding comments
Although the achievement of the goal of complete
regeneration of the periodontal tissues (cementum,
periodontal ligament and bone) for periodontal
management may not be possible for many years (4,
74), recent developments in nanomaterials and
nanotechnology have provided a promising insight
into the commercial applications of nanomaterials in
the management of periodontal diseases (59). A large
number of materials scientists have devoted their
efforts to the development of new nanomaterials;
however, a need exists for them to collaborate more
closely with dentists and dental scientists.
While current work is focused on the recent
development particularly of nanoparticles (10, 11,
34, 36, 67, 82) and nanotubes (15, 26, 50, 54) for
periodontal management, the materials developed
from them such as the hollow nanospheres (9),
core-shell structures (67), nanocomposites (55, 56),
nanoporous materials (61, 63, 75), and nanomem-
branes (26, 31, 60) will play a growing role in
materials development for the dental industry.
Although many studies have been published con-
cerning nanocomposite (48, 51, 55, 71, 82) and
nanoporous materials (1, 64, 83) it will become of
increasing importance to specifically develop
nanomaterials for the management of periodontal
diseases. It is envisaged that this trend will be
further improved in the future as more and more
nanotechnologies are commercially explored.
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