Cutting-edge filler technologies to release bio-active components for restorative and preventive dentistry

Abstract

Advancements in materials used for restorative and preventive treatment is being directed toward “bio-active” functionality. Incorporation of filler particles that release active components is a popular method to create bio-active materials, and many approaches are available to develop fillers with the ability to release components that provide “bio-protective” or “bio-promoting” properties; e.g. metal/calcium phosphate nanoparticles, multiple ion-releasing glass fillers, and non-biodegradable polymer particles. In this review paper, recent developments in cutting-edge filler technologies to release bio-active components are addressed and summarized according to their usefulness and functions, including control of bacterial infection, tooth strengthening, and promotion of tissue regeneration.

Full text

INTRODUCTION
The basic mechanical, physical, esthetic, and bonding
properties of dental restorative/coating materials have
greatly improved with technological developments, and
the current materials on the market show excellent
clinical performance. Therefore, the target of their
advancement is shifting towards bio-active functionality
to prevent primary/secondary diseases or promote tissue
regeneration1,2). Several properties are considered to be
useful bio-active functions for dental materials. These
involve the addition of bio-protective effects, such as
control of bacterial infection or strengthening of the tooth
substrate, and the conferring of bio-promoting effects,
such as remineralization, control of inammation, or
promotion of tissue regeneration2).
Incorporation of ller particles that release active
components is a potential method to create bio-active
materials. Many approaches are available to develop
llers with the ability to release active agents, and
intensive studies have been conducted on ion-releasing
inorganic llers1,3-6). Considering the diverse functions
exhibited by various kinds of ions, several restorative
or coating materials incorporating glass llers with
multiple ion-releasing effects have been commercialized
and are in clinical use1,6). Another technology of interest
is a new ller made of non-biodegradable polymer
particles2), which work as a reservoir to release not only
chemicals but also proteins, and can be incorporated
into restorative/prosthetic materials.
In this review paper, recent developments in
cutting-edge ller technologies to release bio-active
components are summarized, and their effectiveness
examined, focusing on functions to control bacterial
infection, strengthen the tooth substrate, and promote
tissue regeneration.
CONTROL OF BACTERIAL INFECTION
The control of bacterial infection to prevent disease is
a popular function to be added to restorative/coating
materials. One major approach that has been intensively
investigated for resins is to immobilize antimicrobial
components in/on the materials by incorporating
a polymerizable bactericide such as quaternary
ammonium compound (QAC)-based resin monomers. 12-
methacryloyloxydodecylpyridinium bromide (MDPB),
developed by Imazato et al. is representative of
antibacterial QAC monomers7,8), and a prepolymerized
resin ller with immobilized MDPB for resin composites
has also been reported9). In current extensive studies,
many kinds of QAC monomers, such as methacryloxylethyl
cetyl dimethyl ammonium chloride (DMAE-CB)10),
2-methacryloxylethyl dodecyl methyl ammonium
bromide (MAE-DB)11), bis(2-methacryloyloxyethyl)
dimethylammonium bromide (IDMA-1)12),
dimethylaminohexadecyl methacrylate (DMAHDM)13,14),
[2-(methacryloyloxy)ethyl] trimethylammonium chloride
(MADQUAT)15), urethane dimethacrylates quaternary
ammonium methacrylate (UDMQA)16,17), and quaternary
ammonium bis-phenol A glycerolate dimethacrylate
(QABGMA)18) have been developed. Moreover, the
advancement of nanotechnology makes it possible
to develop antibacterial dental resins with QAC-
Cutting-edge ller technologies to release bio-active components for restorative
and preventive dentistry
Satoshi IMAZATO1,2, Tomoki KOHNO2, Ririko TSUBOI2, Pasiree THONGTHAI1, Hockin HK XU3
and Haruaki KITAGAWA1
1 Department of Biomaterials Science, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan
2 Department of Advanced Functional Materials Science, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871,
Japan
3 Department of Advanced Oral Sciences and Therapeutics, University of Maryland School of Dentistry, Baltimore, MD 21201, USA
Corresponding author, Satoshi IMAZATO; E-mail: imazato@dent.osaka-u.ac.jp
Advancements in materials used for restorative and preventive treatment is being directed toward “bio-active” functionality.
Incorporation of ller particles that release active components is a popular method to create bio-active materials, and many approaches
are available to develop llers with the ability to release components that provide “bio-protective” or “bio-promoting” properties;
e.g. metal/calcium phosphate nanoparticles, multiple ion-releasing glass llers, and non-biodegradable polymer particles. In this
review paper, recent developments in cutting-edge ller technologies to release bio-active components are addressed and summarized
according to their usefulness and functions, including control of bacterial infection, tooth strengthening, and promotion of tissue
regeneration.
Keywords: Bio-active, Filler, Restorative materials, Preventive dentistry, Release
Color gures can be viewed in the online issue, which is avail-
able at J-STAGE.
Received Oct 15, 2019: Accepted Oct 25, 2019
doi:10.4012/dmj.2019-350 JOI JST.JSTAGE/dmj/2019-350
Review
Dental Materials Journal 2020; : –

Fig. 1 Antimicrobial properties conferred by contact
inhibition of immobilized bactericide (A) and
controlled release of antimicrobial components
(B).
Fig. 2 Transmission electron microscope image of silver
nanoparticles dispersed in Bis-GMA/TEGDMA
resin.
The silver nanoparticles appear as black dots
(arrow).
functionalized nanollers. Quaternary ammonium
polyethylenimine (QPEI) and silica-based nanoparticles
(QASi) have been reported as llers of resin
composites19,20).
Another major approach to provide dental materials
with bacterial-controlling effects is to apply a carrier
for the delivery of antimicrobial components. Whereas
the antibacterial effects of immobilized QAC depend on
direct contact with bacteria, drug-release systems are
effective in inhibiting bacteria not only on the surface
but also at some distance away from the material (Fig.
1). However, a conventional approach to incorporating
antimicrobial components directly into the materials
limits the duration of the antimicrobial effects to a short
period. Additionally, direct incorporation of additives
compromises the physical properties of the materials
and hampers their integrity for permanent restorations.
Application of drug carriers such as ller particles is an
effective way to overcome these problems, enabling long-
lasting antimicrobial effects with less adverse inuence
on physical/mechanical properties.
Metal nanoparticles
Nanoparticles have been used to improve the
polishability or gloss stability of restorative materials3).
According to ISO/TR 10993-22 and ISO/TR 80004-1,
the nanoscale length range is approximately 1–100 nm,
and nanoparticles are nano-objects with all external
dimensions at the nanoscale. The high surface-area-
to-volume ratio of nanoparticles offers high biological
effectiveness at low concentrations. Metals have been
used for centuries as antimicrobial agents, and the use
of metal nanoparticles composed of silver, copper, zinc
oxide, titanium dioxide, and platinum as llers with
antimicrobial effects has been reported21-24).
Silver has antibacterial, antifungal and antiviral
activity25). Silver ions strongly interact with thiol
groups of vital enzymes and inactivate them, causing
DNA to lose the ability to replicate and leading to cell
death26). Therefore, silver ions have been incorporated
into resinous materials to provide antimicrobial effects.
However, this method does not provide continuous
delivery of silver ions27). Compared with free silver
ions, silver nanoparticles incorporated into a polymeric
matrix work as a large reservoir of silver ions that can
be released in a controlled manner at a steady rate,
allowing for long-term antibacterial effects28).
The direct incorporation of silver nanoparticles into
a polymer matrix is a common method of preparing
antibacterial resinous materials29). However, silver
nanoparticles are difcult to disperse, since nano-sized
particles tend to aggregate and agglomerate. To prevent
the aggregation, silver nanoparticles are stabilized by
various functional groups on their surface using coating
agents or stabilizers such as polymers, polysaccharides,
or citrates30,31).
Another unique approach to avoid aggregation in
resinous materials is a technique for preparing dental
polymers with evenly dispersed silver nanoparticles
using coupling photo-initiated free radical polymerization
of dimethacrylates with in situ silver ion reduction32)
(Fig. 2). Experimental composites containing 0.08%
silver nanoparticles exhibited a 40% reduction in
bacterial coverage32). The antibacterial activity of the
nanocomposites is thought to be due to the release of
silver ions from the nanoparticles. As opposed to QAC
monomer-containing resins whose inhibitory effects
2
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Fig. 3 Scanning electron microscope image of BioUnion
ller.
Fig. 4 Schematic diagram of ion release from BioUnion
ller.
depend on contact inhibition of bacteria, resinous
material incorporating silver nanoparticles can inhibit
bacteria suspended in culture medium as well as on its
surface33) (Fig. 1). Therefore, QAC monomers and silver
nanoparticles could show complementary behavior
for inhibiting bacteria. Experimental adhesives or
endodontic resin-based sealers containing dual agents
composed of QAC monomers and silver nanoparticles
signicantly enhanced antibacterial potency before and
after curing compared with those using either agent
alone34,35).
Although silver nanoparticle llers in resinous
materials exhibited strong antimicrobial effects, the color
of the resin become darker due to the plasmon effect of
the particles. It has been argued that this discoloration of
resinous materials is a signicant problem in an esthetic
region. Therefore, other antibacterial nanoparticles
have been used as llers for resinous materials. Zinc
oxide powders, incorporated as opaque reinforcing llers
in resin composites36), display antimicrobial properties
by blocking the synthesis of bacterial cell walls6,37). Zinc
acts directly by altering cell proteins via processes such
as transmembrane proton translocation, or indirectly
by inhibiting protease-induced bacterial adhesion37-39).
Sevinç and Hanley22) reported that zinc oxide
nanoparticles blended as a 10% (w/w) fraction into resin
composites reduced the growth of Streptococcus sobrinus
biolm by 80% compared with unmodied composites.
Nanoparticles composed of zinc are expected to exhibit
antibacterial effects with less inuence on the esthetic
properties of restorative materials compared with silver
nanoparticles.
Ion-releasing glass llers: single ion-releasing type
Hench et al. developed a so-called bioactive glass
composed of SiO2, Na2O, CaO, and P2O5, designated as
bioglass 45S5 and commercially known as Bioglass®5,40).
This glass is a potential candidate for use as ller
particles in restorative materials, because it enhances
hard tissue regeneration and exerts some antimicrobial
effects by releasing ions41,42). Its antimicrobial effects
are attributed to the release of ions such as calcium
ions, which cause neutralization of the local acidic
environment and lead to a local increase in pH that is
not well tolerated by bacteria42,43). Khvostenko et al.44)
reported that resin composites containing another type
of bioglass (65S) reduced bacterial penetration into the
marginal gaps of simulated tooth restorations. Davis
et al.45) developed glass llers containing calcium and
uoride prepared by the sol-gel method. It was shown
that resin composites incorporating these llers acted
as a single source of both calcium (Ca2+) and uoride
(F−) ions in aqueous solutions, and that the composites
could be readily recharged with F−. However, because
the effective concentration of Ca2+ and F− ions against
microorganisms is so high, the antimicrobial effects of
a local increase in pH due to calcium ions from bioglass
45S5 or 65S or the release of uoride ions from uoride-
containing glass llers are limited6). As a result, additional
components are needed to more effectively demonstrate
antibacterial effects against oral microorganisms.
Ion-releasing glass llers: multiple ions-releasing type
Recently, much attention has been paid to glass llers
that show diverse effects by releasing multiple ions.
BioUnion ller (Fig. 3) is a glass powder composed of
SiO2, ZnO, CaO, and F, and can be categorized as a bio-
functional multi-ion-releasing ller. These glass particles
have a silicon-based glass structure and are capable of
releasing zinc (Zn2+), Ca2+, and F− (Fig. 4). A tooth surface
coating composed of BioUnion llers (Caredyne-Shield,
GC, Tokyo, Japan) and a dental cement for root surface
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Fig. 5 Acidity-induced release of zinc ions from BioUnion ller.
Fig. 6 Structure of S-PRG ller and release of multiple
ions.
restoration containing BioUnion llers (Caredyne-
Restore, GC) have been commercialized.
Zn2+ is known to exhibit antibacterial effects against
oral bacteria37,46). The MIC/MBC values of zinc against S.
mutans were reported to be lower than those of uoride6).
Interestingly, Liu et al.6) reported that BioUnion llers
demonstrated accelerated release of Zn2+ under acidic
conditions and exerted strong bactericidal or inhibitory
effects against oral bacteria. Once dental plaque is
formed on the surface of teeth or materials, the pH
values in the area are decreased by acids produced from
oral bacteria such as S. mutans. When these acidogenic
bacteria produce acids, BioUnion llers incorporated
into materials are capable of effectively releasing Zn2+.
Such acidity-induced release of Zn2+ has the potential
to effectively hinder plaque formation on the surface of
materials (Fig. 5).
A surface pre-reacted glass-ionomer (S-PRG)
ller is another technology of interest that releases
multiple ions1). This ller is prepared via an acid-base
reaction between uoroboroaluminosilicate glass and a
polyacrylic acid. The pre-reacted glass-ionomer phase
on the surface of the glass core allows S-PRG ller to
release and recharge F−47,48). Moreover, S-PRG ller
releases aluminum (Al3+), borate (BO33−), sodium (Na+),
silicate (SiO32−), and strontium (Sr2+) ions from the
uoroboroaluminosilicate glass core (Fig. 6). Several
studies have demonstrated that resin composites
containing S-PRG llers exhibit antibacterial effects
against oral bacteria49,50). Miki et al.49) examined the
inhibitory effects of experimental resin composites
containing different ratios of S-PRG llers on S. mutans
growth, and found that the specimens containing
S-PRG ller at 13.9 (vol)% or greater inhibited bacterial
growth on their surfaces. They further demonstrated
that the inhibitory effects shown by the experimental
resin composites were mainly attributed to release of
BO33− and F−. It was also reported that eluate from the
S-PRG ller suppressed the adherence of S. mutans51),
and thus S. mutans biolm formation could be inhibited
on the surface of resin composites containing S-PRG
llers (Fig. 7). Further in vivo studies demonstrated
that commercially available resin composites containing
S-PRG llers (Beautil II, Shofu, Kyoto, Japan)
signicantly inhibited dental plaque accumulation on
their surface after intraoral exposure for 24 h compared
with control composites without S-PRG llers50) (Fig. 8).
Recent investigation of the association of the eluate
from S-PRG ller with bacterial metabolism by Kitagawa
et al.52) revealed that S. mutans glucose metabolism and
acid production could be inhibited by low concentrations
of BO33− or F− at which bacterial growth was not affected.
Nomura et al.53) reported that the eluate from S-PRG
llers effectively inhibited S. mutans growth through
downregulation of operons related to S. mutans sugar
metabolism, resulting in attenuation of the cariogenicity
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Fig. 7 Inhibitory effects of S. mutans plaque formation on resin composites containing
S-PRG ller.
Fig. 8 In vivo plaque accumulation after 24 h in the oral environment.
of S. mutans. Indeed, a coating resin containing S-PRG
llers (PRG Barrier Coat, Shofu), which produces a
coating layer with a thickness of approximately 200 µm,
inhibited the fall in pH induced by glucose consumption
by S. mutans on the material surface54).
Ion release from S-PRG llers is effective in
suppressing the activity of periodontal pathogens. The
eluate of S-PRG llers shows inhibitory effects on the
protease and gelatinase activity of Porphyromonas
gingivalis51). Using animal studies, Iwamatsu-
Kobayashi et al.55) reported that the eluate from S-PRG
llers demonstrated preventive effects against tissue
destruction in periodontal disease. It was also found that
the coaggregation of P. gingivalis and Fusobacterium
nucleatum could be prevented in the presence of S-PRG
ller eluate51), indicating that the release of ions may
contribute to the prevention of periodontitis.
Polymer particles as a reservoir of antimicrobials
Another approach to providing restorative materials
with long-lasting antimicrobial effects is to apply
non-biodegradable polymer particles as a reservoir
of antimicrobials2). Imazato et al. developed non-
biodegradable polymer particles made of hydrophilic
monomer 2-hydroxyethyl methacrylate (HEMA)
and a cross-linking monomer trimethylolpropane
trimethacrylate (TMPT)2) (Fig. 9). Cetylpyridinium
chloride (CPC), a QAC, was loaded into these polymer
particles by two different methods56). One method was
to immerse the particles into a CPC aqueous solution
to uptake CPC. The other method was to add CPC
powder to the HEMA/TMPT monomer mixture and cure
it to produce polymers. Using the immersion method,
it was found that the polymer particles consisting of
50% HEMA/50% TMPT were useful for loading and
release of CPC. Using the pre-mixing method, there
was a marked extension of the release period compared
with that of the immersion method. The CPC-pre-mixed
polymer particles achieved a longer period of CPC-
release over 120 days, and demonstrated antimicrobial
effects against oral bacteria. Moreover, the combination
of pre-mix loading of CPC powder and recharging using
a CPC solution was effective in achieving persistent
antimicrobial effects with sustained release of CPC.
Application of the polyHEMA/TMPT particles loaded
with CPC to resin-based endodontic sealers or denture
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Fig. 9 Non-biodegradable polymer particles made of HEMA and TMPT.
bases/crowns promises to increase the effectiveness
of treatments by conferring properties that inhibit
bacterial infection2).
TOOTH STRENGTHENING
The effects of uoride, calcium and phosphate ions
on promoting mineralization and improving the acid
resistance of enamel and dentin have been reported.
Ion-releasing materials have the potential to inhibit
demineralization and enhance remineralization of teeth,
leading to cessation or prevention of caries.
Calcium phosphate llers/nanoparticles
Amorphous calcium phosphate (ACP) can release
calcium and phosphate ions that are favorable for tooth
mineralization. In vitro studies revealed that resin
composites containing calcium phosphate llers could
release calcium and phosphate ions to supersaturated
levels for apatite precipitation on enamel57-59). However,
the incorporation of ACP decreased the exural strength
of resin composites to about half that of unlled resin58).
Such a low strength was inadequate to make these
composites acceptable as restorative materials60).
To develop experimental composites with the ability
to release high concentrations of calcium and phosphate
ions and with acceptable mechanical properties, Xu et
al. combined nano-sized dicalcium phosphate anhydrous
(DCPA) with silica-fused whiskers as co-llers61-64). With
the high surface area of nanoparticles, large amounts
of calcium and phosphate ions can be released from a
small number of particles. This leaves room in the resin
composite for a signicant amount of silica-fused whiskers
to reinforce the mechanical properties. However, silica-
fused whisker-reinforced nanocomposite is relatively
opaque with a whitish color owing to a refractive
index mismatch between the whiskers and the resin,
and cannot be light-cured65). To solve these problems,
nanoparticles of amorphous calcium phosphate (NACP;
diameter=116 nm) were synthesized via a spray-drying
technique66,67). The boroaluminosilicate glass particles
were combined with NACP to yield light-curable and
weight-bearing particles, and experimental composites
incorporating these llers were prepared. One advantage
of the calcium phosphate llers is that they promote the
release of Ca2+ and phosphate ions (PO43−) under acidic
conditions (pH 4.0)66), and then rapidly neutralize the
acids from pH 4.0 to 5.69 within 10 min68). These effects
combat acidity-induced mineral loss. In addition, NACP-
containing resin composites are capable of effectively
remineralizing demineralized human enamel after a
30-day demineralization/remineralization cycle69). The
remineralization effects were 4-fold stronger than those of
a commercial uoride-releasing composite. Furthermore,
Xu et al. conducted an approach to combine ACP with
antibacterial components (QAC monomer and/or silver
nanoparticles), and created a novel dental bonding
agent with remineralization capacity and long-lasting
antibacterial activity70-73). Such new materials having
both remineralization and antibacterial properties may
be of great benet to prevent secondary caries.
Ion-releasing glass llers
Bioglass 45S5, developed by Hench in 1969, can bind
to hard tissues and stimulate tissue mineralization40),
showing the ability to remineralize enamel and
dentin74,75). The adhesion of resin-modied glass
ionomer to dentin has also been shown to be enhanced
by bioglass 45S5 application76). A resin adhesive
containing bioglass 45S5 improves the nano-mechanical
properties of demineralized dentin77). The incorporation
of bioglass 65S into a dentin desensitizer can reduce
uid ow in dentinal tubules, resulting in reduced
dentinal hypersensitivity78). Jang et al.79) revealed that
the incorporation of 65S signicantly increased the
micro-hardness of the adjacent demineralized dentin,
and calcium phosphate peaks on the dentin could
be detected by attenuated total reection Fourier-
transform infrared spectroscopy (ATR-FTIR) analysis.
These ndings suggest that resin composites containing
65S can remineralize adjacent demineralized dentin.
S-PRG llers modulate the pH of the surrounding
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Fig. 10 Amount of mineral loss in bovine dentin after an
in vitro remineralization test.
A cement containing BioUnion ller (Caredyne-
Restore [BU]), conventional glass ionomer
cement (Ketac Universal Aplicap [KU]) and resin
composites (Gracel Zeroo [GZ]) were coated on
the surface of demineralized bovine root dentin
and stored in a remineralization solution for 4
weeks. Specimens without any materials served
as the control. The amount of mineral loss was
measured by transmission X-ray images of each
specimen. Different letters indicate signicant
differences between the groups (p<0.05, ANOVA,
Tukey’s HSD test, n=5, error bars indicate S.D.).
medium and shift the pH to neutral and weak alkaline
regions80). The release of uoride and silica from
resins incorporating S-PRG llers promotes apatite
formation on phosvitin-immobilized agarose beads in
the presence of a mineralizing solution81). Fluoride can
also improve the acid resistance of the tooth substrate
through the formation of uoroapatite. In vitro studies
have demonstrated that ions released from S-PRG
ller-containing adhesive48) or endodontic sealer82) can
be taken up by the enamel and dentin adjacent to the
material, and the corresponding areas showed decreased
demineralization following acid exposure. Similar
results have also been reported for other S-PRG ller-
containing materials such as orthodontic adhesives83),
ssure sealants84), coating materials54,85), resinous
vanishes86) and denture base resins87). Uo et al.88)
investigated the local structure of strontium taken up
by teeth using X-ray absorption ne structure analysis,
and revealed that the strontium content in enamel and
dentin was 100 times greater after immersion in the
eluate of S-PRG ller than before immersion. It is known
that strontium enhances the acid resistance of teeth
by converting hydroxyapatite to strontiumapatite89,90).
The structure of Sr in the enamel and dentin after
immersion in the eluate of S-PRG ller was similar to
that of synthetic Sr incorporated into hydroxyapatite.
The Sr released from S-PRG ller would be incorporated
into the Ca site of hydroxyapatite. Thus, Sr incorporated
into hydroxyapatite may improve the acid resistance
and remineralization of enamel and dentin.
BioUnion ller exhibits not only antibacterial
effects but also inhibition of demineralization and
enhancement of remineralization in tooth structure91).
Zinc demonstrates an inhibitory effect against
demineralization of enamel92) and dentin93), and inhibits
the activity of matrix metalloproteinase (MMP)94). It is
well known that F− and Ca2+ released from BioUnion ller
inhibit demineralization and enhance remineralization of
teeth95,96). Cement containing BioUnion ller (Caredyne-
Restore) exhibited superior enhancement of root dentin
remineralization when compared with conventional
glass ionomer cement and resin composite (Fig. 10).
PROMOTION OF TISSUE REGENERATION
Although extensive research on tissue regeneration is
being undertaken in a variety of medical elds, there
are few studies investigating llers for dental materials
with the ability to promote tissue regeneration.
Several studies have revealed that active components
incorporated into inorganic or resin cements promote
tissue formation or regeneration as well as cell
proliferation and differentiation.
Ion-releasing glass llers
Strontium is known to promote osteogenic differentiation
of mesenchymal stem cells and suppress the activity
of osteoclasts97). The administration of strontium has
been shown to increase bone density and decrease
the incidence of fractures in vertebral and peripheral
bones98). Sasaki et al.99) fabricated strontium-doped
glass that was incorporated into glass ionomer cements.
These experimental cements promoted the alkaline
phosphatase activity of osteoblasts without the need for
any media supplements for osteoblastic differentiation.
Apart from its anti-plaque and remineralization
effects, S-PRG ller has the ability to promote tertiary
dentinogenesis. Experimental cements as pulp capping
materials were prepared by mixing S-PRG llers with
copolymers of acrylic acid and tricarboxylic acid. After
pulp exposure in rat molars, the experimental cement
exhibited complete tertiary dentin formation at 2 and
4 weeks due to the release of multiple ions such as Sr2+,
BO33−, F−, or SiO32− 100). Okamoto et al.101) reported that
S-PRG cement regulated the expression of genes related
to osteo/dentinogenic differentiation. CXCL-12 and TGF-
β1 were upregulated following ion release from S-PRG
ller and may contribute to tertiary dentin formation
during the healing process in pulpal tissue.
Polymer particles as a reservoir of antimicrobials
The non-biodegradable polyHEMA/TMPT particles
described before can also act as a carrier for growth
factors. Takeda et al.102) reported that broblast growth
factor-2 (FGF-2) could be loaded into polymer particles
composed of 90 (wt)% HEMA and 10 (wt)% TMPT,
and FGF-2 adsorbed to the particles was released
over 14 days and maintained its activity in increasing
the proliferation of osteoblast-like cells. Additionally,
when the FGF-2-loaded polymer particles were
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Fig. 11 Optical microscope images of MC3T3-E1 cells cultured in the presence of
4-META/MMA-based resin incorporating FGF-2-unloaded (A) and FGF-2-
loaded (B) polymer particles.
Each resin disc was placed in a 48-well plate, and MC3T3-E1 cells were seeded
in each well at 5×103 cells/well and cultured for 3 days. More cells were observed
around the resin incorporating FGF-2-loaded polymer particles (B) compared
with the resin incorporating FGF-2-unloaded polymer particles (A).
incorporated into 4-META/MMA-based adhesive resin,
the experimental resin released FGF-2 for 14 days103).
Such sustained release of FGF-2 from the experimental
resin promoted cell proliferation (Fig. 11), and induced
bone regeneration of rat calvaria implanted with
experimental resin incorporating polymer particles103).
This nding suggests that adhesive resins incorporating
FGF-2-loaded polymer particles could be applied to root-
end llings, perforation sealing, or the repair of fractured
roots in cases with severely damaged periodontal
tissue2).
CONCLUSIONS
The ller technologies to create “bioactive” materials
described here have great potential to contribute to
successful restorative and preventive treatments. Many
of these materials demonstrate possible benets in vitro
or under clinically-relevant experimental conditions.
New generation materials with “bio-active” functions,
including commercially available materials that contain
BioUnion ller or S-PRG ller, require further intensive
research to show that they can provide substantial
benets in clinical settings. For such purposes, it is
meaningful to develop convenient in vitro evaluation
systems that are specically designed for “bio-active”
materials, with realistic simulations of the oral
environment.
ACKNOWLEDGMENTS
This work was supported in part by Grants-in-Aid for
Scientic Research (Nos. JP17H04383, JP18K17044,
JP18H06292, JP19K19024) from the Japan Society for
the Promotion of Science.
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