International Journal of Applied Glass Science 1–13 (2013)

DOI:10.1111/ijag.12029

Nanoscale Bioactive Glasses in Medical Applications

Melek Erol-Taygun
Department of Chemical Engineering, Chemical and Metallurgical Engineering Faculty,
Istanbul Technical University, Maslak 34469, Istanbul, Turkey

Kai Zheng and Aldo R. Boccaccini*,†

Institute of Biomaterials, University of Erlangen-Nuremberg, 91058 Erlangen, Germany

This review focuses on recent advances in the development and use of nanoscale silicate bioactive glasses for medical
applications. In the context of materials for bone substitution, dental applications, and bone tissue engineering, nanoscale bio-
active glasses have been gaining attention due to their expected superior osteoconductivity when compared with conventional
(micrometer-sized) bioactive glass materials. A detailed overview of recent developments in the field of nanoscale bioactive
glasses will be given, including a summary of common fabrication methods and diverse application areas which include tissue
engineering scaffolds and coatings, drug delivery devices, and dentistry. The nanofeatures characteristic of this type of bioac-
tive glasses and the possibilities to expand their use in biomedical applications (nanomedicine) are highlighted.

Introduction key properties determining the cell–biomaterial inter-

Nanotechnology approaches are being proposed for
a wide variety of medical engineering and biomedical
applications in what is termed nanomedicine. Nano-
science and nanotechnology are particularly attractive in
relation to regenerative medicine and tissue engineering
approaches as the interactions between cells and bioma-
terial surfaces occur firstly in the nanoscale (e.g.,
<100 nm), and the components of biological tissues
have nanoscale dimensions.1,2 In the nanometer scale,
*Member, The American Ceramic Society.
†
aldo.boccaccini@ww.uni-erlangen.de
© 2013 The American Ceramic Society and Wiley Periodicals, Inc
action such as surface area, surface roughness, hydro-
philicity, and wettability, which influence cell adhesion
and provide bonding properties to host (bone) tissue
for long-term functionality, are fundamentally different
from those in the conventional (micrometer) scale.3,4
Over the last four decades, bioactive glasses have been
considered for applications in orthopedic devices and
dentistry, and they play an increasingly important role
in bone tissue engineering applications by virtue of their
excellent osteoconductivity, that is, the bone growing
ability on an implant surface, bioactivity, and generally
tailorable degradation rate.5,6 Several different types of
bioactive silicate glasses in a variety of compositions
2 International Journal of Applied Glass Science—Erol-Taygun, Zheng, and Boccaccini

incorporating metallic ions with specific cellular effects Properties of Nanosized Bioactive glasses
on cells have been investigated for their potential use
for bone tissue regeneration.7 The first bioactive glass Bioactivity and Bone Bonding
(BG), known as 45S5 Bioglassâ (in wt%: 45% SiO2,
The typical feature of BGs is their high surface
24.5% Na2O, 24.5% CaO and 6% P2O5), discovered
reactivity (or bioactivity8), which enables the effective
by Hench et al.,8 has been widely investigated for
interaction of the material with host tissue, leading to
numerous biomedical applications. It has been consid-
strong bone (and in some cases soft) tissue attachment.
ered in clinical treatments of periodontal diseases as
The bonding to bone has been traditionally explained
bone filler as well as in middle ear surgery.8 Other BG
by considering the formation of a carbonated hydroxy-
compositions developed over the years incorporate dif-
apatite surface layer on BGs when they are in a biologi-
ferent elements in the silicate network such as magne-
cal environment,5,8 which is usually determined in
sium, strontium, silver, copper, boron, potassium,
simulated body fluid (SBF), for example, by norm
lithium, fluoride, or zinc.9–14 The application of BGs
ISO23317. The sequence of reactions on the glass sur-
in bone tissue engineering is attractive also for the spe-
face involves ion leaching/exchange, dissolution of the
cific effect of dissolution products from BGs on cellular
glass network and precipitation, and growth of the
response, for example, upregulating the expression of
hydroxyapatite surface layer followed by cellular reac-
genes that control osteogenesis15 or enhancing secretion
tions. The relevance of the nanoscale in relation to the
of vascular endothelial growth factor (VEGF) in vitro
bioactive behavior of bioactive glasses is related to the
to induce vascularization in vivo.16–19 It is also well
higher specific surface area of nanoscale bioactive glasses
known that the incorporation of specific ions in the sil-
(nanoparticles and nanofibers) which should induce a
icate network, such as Ag or Zn, leads to antibacterial
faster solubility of the material (due to higher ion
materials.20–22 Bioactive glasses can also serve as vehicle
release rates) and also a higher protein adsorption abil-
for the local delivery of selected ions which can control
ity, which is expected to increase the bioactivity.31
specific cell functions,7 as carrier of bioactive molecules
Indeed, it has been shown that increased deposition or
and therapeutic drugs23–25 and as hemostatic agents.26
mineralization of tissues such as bone or teeth is possi-
Moreover, ferromagnetic bioactive glasses containing
ble when these tissues are in contact with ceramic
magnetite are being developed for hyperthermia treat-
nanoparticles.32 Nanoscale bioactive glasses are thus
ment of cancer.27 The application of bioactive glasses is
attractive because they can be used to mimic the nano-
being expanded to consider applications in contact with
features of the mineral phase of bone which should
“soft” tissues, for example, incorporated into polymer
increase bone-forming cell adhesion and proliferation,
composites for nerve regeneration,28 or for intestinal
as shown also for other nanoparticles.32
tissue engineering.29
The attraction of combining nanotechnology
approaches with the field of bioactive glasses becomes
In Vitro Cellular Response
clear considering that relevant properties and the bio-
logical behavior of bioactive glasses can be influenced The composition of BGs usually determines the
and controlled to a greater extent in the nanoscale, for ability of the material to support the proliferation and
example, using nanoparticles or nanofibers, for a range function of osteoblastic cells.7,33 In addition, the BG
of applications including orthopedic coatings, dental particle size affects the interaction with cells, especially
filling materials, biocomposites for biodegradable in the nanoscale, considering the nanostructured
implants, tissue engineering scaffolds, or drug delivery arrangement of the extracellular matrix components. It
vehicles. This review presents a complete overview on is well known and increasingly investigated that nano-
recent developments in the field of nanosized BG scale features of materials affect their textural proper-
(NBG) particles and nanofibers for biomedical applica- ties, surface energy and chemistry, nanotopography and
tions. Mesoporous BGs, which exhibit ordered nano- wettability, and control protein interactions modulating
scale porosity to impart functionality, for example, subsequent cell adhesion, and long-term functional-
nanotopography and drug delivery ability, are not con- ity.3,32,34 In the particular case of BG of 45S5
sidered here, comprehensive related publications are Bioglassâ composition, it was shown that when nano-
available.23,24,30 particles instead of micrometer-sized particles were used
www.ceramics.org/IJAGS Nanoscale Bioactive Glasses in Medical Applications
as filler in biopolymer matrix composites, the total pro-
tein adsorption was improved.35 It was also reported36
that the ALP activity of MG-63 cells on nanoparticu-
late BG containing composites was considerably higher
than that on the control surface. In a recent study,
Gong et al.37 reported similar results with nanoscaled
58S bioactive glass. It was stated that the ionic dissolu-
tion of nano 58S bioactive glass can induce improved
cell proliferation and higher mRNA expression of ALP,
Cbfal, and OCN compared with micro 58S bioactive
glass. Chondrocyte cell behavior on 63S bioactive glass
nanoparticles was evaluated by Doostmohammadi
et al.38 who found that cells can grow and proliferate
at low nanoparticle concentration. The effect is also rel-
evant when NBG particles are embedded in biodegrad-
able polymers.39
Ion Dissolution: Effects on Osteogenesis and
Angiogenesis
BGs are interesting also as vehicles for the local
delivery of selected ions being able to control specific
cell functions.7 Key mechanisms leading to enhanced
new bone growth are expected to be closely related to
the controlled release of ionic dissolution products from
the degrading BG. This involves critical concentrations
of silica and calcium ions but also a wide range of
other metallic ions being incorporated in silicate BGs,
as reviewed elsewhere.7 The ion release rate and thera-
peutic levels are determined by the concentration and
particle size of BGs, which in turn affect the relative
contribution of specific ion dissolution products to
osteogenesis and angiogenesis. Thus, the dissolution of
ion-doped bioactive glasses can be designed to control
the release of critical concentrations of specific metal
ions which can lead to increased osteoblast activity
(e.g., in strontium doped-BG) to beneficial anti-inflam-
matory effects (e.g., in zinc doped-BG) or to angio-
genic effects (e.g., in Co-doped and Cu-doped BGs).
The effect of ion dissolution is also prevalent when
NBG particles are embedded in biodegradable polymers
as shown recently for chitosan-Mg-doped NBG com-
posite films.40 The possible specific angiogenic effect of
nanoscale bioactive glasses, however, has been only scar-
cely considered. Recently, Gerhardt et al.41 investigated
the angiogenic properties of micrometer-sized and
nanosized BG filled composites. It was found that both
micrometer-sized and nanosized BG filled composites
exhibited pro-angiogenic properties. No clear difference
3
between the angiogenic behavior of the micrometer-
sized and nanosized BG fillers was found,41 which
motivates future studies in the field, as nanoscale BG
containing composites are expected to exhibit enhanced
osteoconductivity.35
Mechanical Performance
One of the well-known applications of bioactive
glasses in the biomedical field is for scaffold fabrication
for bone tissue engineering5,33,42–44 as will be discussed
in Section “Applications of Nanoscale Bioactive
Glasses.” A key property, particularly for scaffolds
intended for the repair of load-bearing bone, is the
mechanical response. Scaffolds should have mechanical
properties comparable to those of the tissue to be
replaced.33 Mechanical properties of scaffolds depend
on different parameters including the intrinsic proper-
ties of the BG used and the scaffold microstructure. In
case of composites involving biopolymer matrices and
BG fillers, the filler particle size has an important effect
on the mechanical performance. Biopolymer matrix
composites containing nanoscale BGs have been dis-
cussed elsewhere,45 and it was shown that the use of
BG nanoparticles leads to composite scaffolds mimick-
ing more closely the structure of natural bone. It is
expected that using nanoscale BGs will result in a sig-
nificant improvement of the mechanical properties
(compressive strength, elastic modulus, and tensile
strength) of composite scaffolds, compared with that of
conventional composites containing micrometer-sized
BG.35,46,47
Fabrication of Bioactive Glass Nanoparticles and
Nanofibers
Solgel Methods
Solgel-based methods are well known for the pro-
cessing of inorganic materials, for example, for the fab-
rication of thin films, powders, nanoparticles, and
fibers. The solgel technique is well suited to fabricate
BG nanoparticles: the morphology and size of nanopar-
ticles can be tailored by varying the production condi-
tions and the feeding ratio of reagents.48 Solgel-based
methods have been also applied to fabricate silicate
fibers by electrospinning reaching fiber diameters
<100 nm.49 The resulting BG nanofibers are flexible
due to their small diameter, and they can be used in
4 International Journal of Applied Glass Science—Erol-Taygun, Zheng, and Boccaccini

fibrous bioactive scaffolds. Doping with specific ions is
also possible. For example, Goh et al.50 have recently
produced nanosized bioactive glasses with incorporation
of zinc by solgel method. FESEM analysis of the zinc-
containing BG revealed the formation of spherical
agglomerated particles with diameter ranging from
14 nm to 34 nm. Nanoscale bioactive glass particles
(mean particle size 100 nm) doped with silver have
been also developed by solgel method51 and considered
for antibacterial applications.52 Up to now, almost all
nanoscale BG particles reported have been prepared by
the precipitation of BG sols using alkaline treatment in
a basic environment. More recently, scientists have
attempted to synthesize solgel-derived nanoscale BG by
developing new techniques or by combinations of
methods. For example, in a recent study, Ma et al.53
successfully prepared submicrometer/nano microporous
BG fibers (BGFs) with a relative simple method
through solgel-combined electrospinning technique and
modified St€ober method. They reported that the as-
synthesized fibers are core–shell structured with a con-
densed silica core (cSiO2) and a microporous BG shell
exhibiting an average pore size of 1.7 nm (Fig. 1).53 In
another recent study, Lei et al.54 developed a new tech-
nique to synthesize nanoscale BG (SiO2–CaO–P2O5)
particles using an acid-catalyzed solgel process and gela-
tion-induced phase separation (GIPS) technology. A
base-catalyzed solgel process has been also recently pre-
sented by Luz and Mano55 to synthesize ternary (SiO2-
CaO-P2O5) and binary (SiO2-CaO) nano bioactive
glasses. A related recent study has presented a solgel
low temperature process to produce nano-BG–ceramic
material from 58S BG with b-TCP and pseudowollastonite
as the main crystalline phases formed in the BG–ceramic
samples after calcification of the dried gel.56 Although
there has been increased interest in fabricating solgel-
derived nanoscale BGs, only a limited amount of
studies have paid attention to the biocompatibility and

(a) (c)

(b) (d)

Fig. 1. (a) and (b) SEM images of cSiO2 fibers and core and a microporous bioactive glass (BG) shell (cSiO2@mBG) fibers, wherein
‘‘c’’ means ‘‘condensed’’ and ‘‘m’’ means ‘‘microporous”; (c) TEM image of one single cSiO2@mBG fiber; (d) TEM image of the area
marked with the white box in (c). Inset in (d) shows the selected area electron diffraction (SAED) pattern of the porous BG shell. Accord-
ing to Ma et al.53 (reproduced with permission of Elsevier).
www.ceramics.org/IJAGS Nanoscale Bioactive Glasses in Medical Applications
osteogenic or angiogenic-inducing ability of these novel
solgel-derived nanoscale BGs.
Other Processing Methods
A few other methods have been developed to fabri-
cate nanoscale BGs. One of the proposed methods is
microemulsion. This processing technique is capable of
producing nanosized particles with minimum agglomer-
ation as the reaction takes place in nanosized
domains.57 Using a microemulsion approach, Zhao
et al.58 fabricated spherical nanoparticles of 25–50 nm
size in the system CaO-P2O5-SiO2. Another convenient
fabrication method for nanoscale BGs is the flame
spray synthesis technique, which is a gas phase-based
method that uses metal-organic precursors to produce
nanoparticles at temperatures above 1000°C.59 The
process enables production of numerous nanoparticu-
late mixed-oxides with high chemical homogeneity; by
using this technique, the preparation of nanoparticles
of different BG compositions has become possible.59,60
Another technique involving high temperatures is
laser spinning, this technique has been used to produce
glass fibers with a wide range of diameters (from the
nanometer to micrometer scale).61 This method
involves the fast heating and melting of a small volume
of the precursor material up to high temperatures using
a high power laser. Long fibers with high length to
diameter ratios can be produced, and the obtained
material is in amorphous form because of the high
cooling speed.61,62 More recently, Luz and Mano63
have developed a new nanotechnique for the fabrication
of hierarchically organized bioactive glass nanoparticle-
based macrospheres, which is based on evaporation-
induced self-assembly (EISA). The crystallization degree
of the macrospheres could be tuned by regulating the
evaporation rate of the liquid phase, which can influence
the ionic dissolution of macrospheres. This technique is
simple and highly attractive to produce inorganic
macrospheres based on NBG particles for biomedical
applications and merits further research efforts.
Applications of Nanoscale Bioactive Glasses
Dentistry
Bioactive glasses are well known in the dentistry
field in applications involving de- and remineralization
of dentin, root canal disinfection, dental restoration,
5
augmenting alveolar ridges, and for treating periodontal
pockets and dentin hypersensitivity.60,64 The applica-
tion of BGs as a remineralization agent can be broad-
ened by decreasing BG particle size that leads to
enhanced dissolution of ions from the glass resulting in
acceleration of the remineralization of dentin.65 Curtis
et al.66 have compared the efficiency of an established
BG powder with mean particle size in the micrometer
range with a proprietary nanoscale BG to occlude
exposed dentine tubules and remineralization by the
formation of apatite. It was reported that the treatment
with nanoscale BG resulted in particle deposition
within tubules and formation of apatite rods, which
were tightly adherent to tubule walls and continuous to
a measured depth of 270 lm (Fig. 2).66 BGs are also
interesting for dental applications because of their anti-
microbial effect in closed systems.67 Waltimo et al.64
used nanoscale BG (45S5 BG composition) to impart
antibacterial properties against different Enterococcus
faecalis strains in a direct exposure model. The antibac-
terial effects of nanoscale BGs in different compositions
(28S5, 45S5, 58S, 63S, 72S, and 77S) were also dem-
onstrated by Gubler et al.68 and by Mortazavi et al.69
For extending the dental applications of nanoscale BGs,
Mohn et al.70 developed flame spray-derived nanoscale
BGs incorporating bismuth oxide as a radiopacifier.
NBG particles have been also considered in the field of
regenerative therapy in periodontics.71 The attractive
bioactive properties of BG nanoparticles have been also
exploited in polymer nanocomposites for periodontal
tissue engineering, for example, by developing of algi-
nate-based composite scaffolds using lyophilization
technique and by characterizing the response of human
periodontal ligament fibroblast (hPDLF) and osteosar-
coma (MG-63) cells.72 In a related study, a novel
nanocomposite made of collagen (Col) with NBG par-
ticles was fabricated as a scaffolding matrix for the cul-
ture of human dental pulp cells (hDPCs).73 It was
considered that the addition of NBG affected adhesion-
related cellular responses, providing different or addi-
tional physical cues to hDPCs for their recognition into
the adhesive matrix and further spreading out and
migration. It was emphasized that the nanocomposite
Col/NBG matrix induced the growth and odontogenic
differentiation more effectively than Col alone, being a
promising indication for regeneration of dentin–pulp
complex tissue.73 In a recent study, Mota et al.74 pro-
duced a composite of chitosan (CHT) with NBG parti-
cles (SiO2-CaO-P2O5) as barrier membrane to be used
6 International Journal of Applied Glass Science—Erol-Taygun, Zheng, and Boccaccini

Fig. 2. Focused ion beam (FIB) images (a) highlighting the formation of apatite rods following application of nanosized bioactive glass
to dentine. (b) Cross-sections of apatite rods within tubules were produced by cutting with the ion beam. The apatite rods (arrowed)
appear to completely fill the tubules (circled) and were shown to be continuous. Further SEM observation of transverse sections identified
apatite rods to a maximum depth of 270 lm. According to Curtis et al.66 (reproduced with permission of Elsevier).

in periodontal applications with the aim of supporting
periodontal regeneration by physically blocking migra-
tion of epithelial cells. One of the key issues in den-
tistry is to understand the molecular mechanisms that
regulate periodontal regeneration, for example, cemen-
tum markers. Cementum is a mineralized tissue pro-
duced by cementoblasts during tooth root formation. It
plays a critical role in the reparative process, during
regeneration of tissue after periodontal disease. In this
context, Carvalho et al.75 investigated the effect of
NBG particles (SiO2-CaO-P2O5) on cementoblast
behavior. It was found that the ionic products from
NBG increased cementoblast viability, mitochondrial
activity, and induced cell proliferation which indicates
that they could be a potential material for use in
cement regeneration. Table I provides a comprehensive
summary of the applications of nanoscale BGs in the
dental field. The studies showed that bioactive glass
nanoparticles are capable of inducing cell proliferation
of periodontal ligament, especially cementoblast indi-
cating that NBG is a potential material for use in peri-
odontal tissue regeneration in the near future.76
Orthopedic Coatings
NBG particles can be conveniently applied in the
preparation of novel bioactive and nanostructured
orthopedic coatings. For example, solgel-derived NBG
particles have been used to coat different materials
(porous ceramics, metals) to achieve improved mechan-
ical properties and high bioactivity.77–79 More recently,
Sebdani and Fathi80 fabricated novel hydroxyapatite–
forsterite–BG nanocomposite coating via a solgel
method and evaluated its mechanical properties. It was
stated that improvement of the mechanical properties
could be obtained with increasing forsterite content.
www.ceramics.org/IJAGS Nanoscale Bioactive Glasses in Medical Applications 7

Table I. Dental Applications on Nanoscaled Bioactive Glasses

Method of End product
Composition fabrication shape Key results achieved References
NBG (45S5) Flame spray Slurry with The nanometric slurry has a considerably 60
synthesis nanometric higher alkaline capacity and disinfected
bioactive glass significantly better than the micrometric
powder counterpart
NBG (45S5) Flame spray NBG particles NBG displays a stronger antimicrobial 64
synthesis effect than the currently applied
micrometer-sized material
NBG (45S5) Flame spray Suspensions of Higher remineralization rate induced by 65
synthesis nanometric nanometer-sized vs micrometric
bioactive glass bioactive glass particles
NBG (70S30C) Solgel Slurry with NBG resulted in particle deposition 66
nanometric within tubules and formation of apatite
bioactive glass rods
powder
NBG (28S5, Flame spray Slurry with The amount of sodium and the high 68
45S5 and 77S) synthesis nanometric surface area of NBG is related to the
bioactive glass antimicrobial effect
powder
NBG (58S, Solgel NBG 58S and 63S bioactive glass nanopowders 69
63S, and 72S) show antibacterial activity even at low
concentrations
NBG (45S5) with Flame spray Disks NBG with bismuth oxide is radio- 70
20 wt% synthesis opaque
and 50 wt% of
bismuth oxide
Solgel-derived NBG Lyophilization Porous scaffold Incorporation of NBGC helped to attain 72
(CaO–SiO2–P2O5) good protein adsorption, cell
and alginate attachment, and cell proliferation
NBG Electrospinning Membrane NBG helped to induce the growth 73
(CaO–SiO2–P2O5) and odontogenic differentiation
and collagen more effectively
NBG Solvent Membrane Incorporation of NBG into the 74
(CaO–SiO2–P2O5) evaporation membrane promoted greater cell
and chitosan matrix mineralization
NBG Sol-gel Slurry with NBG increased cementoblast viability, 75
(CaO–SiO2–P2O5) nanometric mitochondrial activity, and induced
bioactive glass cell proliferation
powder

Esfahani et al.81 have also developed titania films incor-
porating 58S NBG particles, and the results revealed the
excellent bioactivity and mechanical properties of the
films suitable for orthopedic coatings. Related calcinated
NBG particles-titania composite films coated on stain-
less steel substrates were investigated by Dadash et al.,82
while Gerhardt et al.41 studied the effect of NBG parti-
cles (incorporated onto decellularized trabecular bone
scaffolds) on the in vivo angiogenic behavior of the
scaffold in a rat model. There is increasing interest in
8 International Journal of Applied Glass Science—Erol-Taygun, Zheng, and Boccaccini

the development of “soft,” for example, polymer-con-
taining bioactive coatings for orthopedic applications
enabling biological moieties to be incorporated in the
coatings (biofunctionalization) for improved bone
bonding.83,84 Moreover, the presence of the polymer as
a binding phase is useful to avoid the high-temperature
densification process required in ceramic-only coatings.
Nanoscale BGs are interesting components of such
novel nanostructured composite coatings.85 For exam-
ple, polymer-NBG composite coatings have been devel-
oped by Couto et al.,48 who used chitosan and
nanoscale BG to prepare multilayered coatings by the
layer-by-layer (LbL) technique. The organic compo-
nent, chitosan, provided viscoelastic properties to the
final coating and NBG induced the required bioactivity
for bone attachment. Polymer-NBG composite coatings
have been also applied onto biphasic calcium phosphate
scaffold.86 Compared with the scaffolds without NBG
coating, significant upregulation of osteopontin, bone
sialoprotein, and osteogenic gene expression for Runx2
was observed demonstrating again the high bioactivity
that NBG particles can impart for bone regeneration.
development of nanocarriers to enhance the effective
targeting in specific cancer regions without destroying
or affecting the viability of nearby normal tissues.91
Novel magnetic degradable solgel glasses have been
developed adding Fe ions into BG (Na2O-CaO-P2O5-
SiO2) as thermoseed for hyperthermia cancer therapy.92
It is known that magnetic biomaterials when exposed
to a magnetic field produce heat within the diseased tis-
sue region. Cancer cells are destroyed at higher temper-
ature (>43 °C), while normal cells survive these
temperatures.93,94 Recently, Jayalekshmi et al.95 have
developed biocompatibility and biodegradable iron
oxide-incorporated chitosan-gelatin NBG composite
particles [Fe-BG]. It was stated that the developed com-
posite nanoparticles successfully generate heat energy by
conversion of hysteresis loss in the presence of an
applied magnetic field. The size of the negatively
charged composite nanoparticle was in the range of
43–51 nm (Fig. 3).95 Results revealed that the devel-
oped that the composite nanoparticle is a soft magnetic
material and is suitable for the magnetic hyperthermia
treatment and drug delivery.

Applications in drug delivery and nanomedicine

Developing advanced drug delivery devices which
exhibit greater efficiency and lower toxicity are at the
center of current investigations, such systems should
enable controlled and prolonged drug release thus lead-
ing to predictable therapeutic response and safety.87 In
this field, mostly mesoporous bioactive glasses and
composites of bioactive glasses and polymers are being
considered, which have the capability for the local
delivery of antibiotics and other antibacterial agents,
anti-inflammatory drugs, growth factors, other proteins
and peptides.23–25 Nanoparticles are also being increas-
ingly investigated as nanocarriers for drugs. These can
penetrate into tissues through fine capillaries and are
generally taken up efficiently by cells.88 Yun et al.89
have synthesized mesoporous bioactive glass (MBG)
nanospheres of SiO2-CaO-P2O5 composition that exhi-
bit large specific surface area and pore volume. Micro-
spheres with high content of CaO showed in vitro
bone-forming ability and favorable in vitro biocompati-
bility. More recently, Huang et al.90 have synthesized
luminescent Eu3+ or Tb3+ doped mesoporous bioactive Fig. 3. TEM image of iron oxide-incorporated chitosan-gelatin
glass nanofibers (MBGNFs) via electrospinning which nanosized bioactive glass (NBG) composite particle [Fe-BG] syn-
demonstrated sustained release properties for ibuprofen thesized by Jayalekshmi et al.95 (Reproduced with permission of
(IBU) in vitro. Further research is focusing on the Elsevier).
www.ceramics.org/IJAGS Nanoscale Bioactive Glasses in Medical Applications
Bone Tissue Engineering Scaffolds
The application of nanoscale bioactive glasses in
tissue engineering is increasing, and numerous studies
are continuously reported in which the attractive prop-
erties of these materials, discussed above, are being
exploited.45 For example, the last 5 years have seen the
development of BG/polymer nanocomposite scaffolds
including synthetic (e.g., Refs. 35, 39, 47) and natural
matrices (e.g., Ref. 48), nanocomposites containing BG
nanofibers,48 and multifunctional composite scaffolds.96
New studies on the fabrication of nanocomposite scaf-
folds have concentrated on the improvement of biologi-
cal and mechanical properties of the scaffolds using
blends of the polymers. In a recent study, Oliveira
et al.97 have produced biodegradable and bioactive
composites with the incorporation of BG nanoparticles
in polyurethane (PU)/PVA blends. It was stated that
the nanocomposite scaffolds presented good cell viabil-
ity and hydroxyapatite layer formation upon immersion
in SBF, which was prepared following the standardized
Kokubo approach. The production of a nanofibrous
bioactive glass and its potential in the enhancement of
bone bioactivity and in vitro osteogenic differentiation
of mesenchymal stem cells (MSCs) has been reported.49
Based on this study, Kim et al.98 recently showed that
the addition of NBG fibers to a biopolymer matrix
increased cell proliferation.
Hydrogels as injectable scaffolds are gaining rele-
vance for several tissue engineering applications because
they enable encapsulation of cells and bioactive agents
in a biodegradable matrix, which can be delivered
through minimally invasive procedures. Couto et al.99
developed injectable biodegradable materials with BG
nanoparticles to produce thermoresponsive hydrogels
for orthopedic reconstructive and regenerative medicine
applications. The inclusion of BG nanoparticles led to
the formation of bone-like apatite clusters well inte-
grated in the hydrogel organic structure.
In one of the few in vivo studies available involving
NBG particles, Hafezi et al.100 fabricated NBG/gelatin
scaffold by particulate freeze-drying techniques and
investigated its in vitro and in vivo bone regeneration
capacity. It was reported that the bioactive nanocom-
posite scaffold made a significant contribution to
growth and healing of bone during 12 weeks
(Fig. 4).100 Recent studies involving the development
of NBG-containing scaffolds for bone tissue engineering
9
have considered alginate,101 collagen,102,103 gelatin,104
chitosan,105,106 and silk fibroin.107 All these composites
have exploited the mineralization ability of NBG parti-
cles in physiological or simulated body fluid to enhance
the bioactivity of the applied biopolymers. A methodol-
ogy to obtain micropatterned NBG particles (BG-NPs)
on chitosan membranes by lCP has been recently
developed,108 which represents an innovative tissue
engineering platform that could have potential applica-
tions in different regeneration fields by combining both
physical and chemical strategies to control cell attach-
ment and apatite deposition. The high bioactivity of
BG-NPs spots allowed nucleation and growth of apa-
tite, highly localized in the patterned regions of the
chitosan membranes. This approach opens new routes
for developing patterned medical membranes with dis-
tinct properties in the two sides, able to promote
guided tissue regeneration in the bone side, while pre-
venting soft tissue growth on the other face. In another
study involving NBG, Moorthi et al.109 investigated
the possible role of solgel-derived NBG (SiO2-CaO-
P2O5) particles on the hierarchical events of bone for-
mation involving proliferation, differentiation, and
mineralization. It was found that NBG particles are
nontoxic to rat osteoprogenitor cells and able to stimu-
late proliferation of the cells. It was also reported that
NBG particles have an effect on stimulation of prolifer-
ation of osteoprogenitor cells. in vitro studies of NBG
particles with alternative compositions (beyond the
common SiO2-CaO or SiO2-CaO-P2O5 systems) are
limited. In a recent study, Prabhu et al.110 have investi-
gated the effect of MgO-substituted NBG particles on
in vitro bioactivity using simulated body fluid (SBF)
and human gastric adenocarcinoma (AGS) cell line. It
was stated that magnesium ion did not impair the for-
mation of an apatite layer, in addition cell attachment
and proliferation were increased. Combination strate-
gies of NBG particles in advanced nanocomposite sys-
tems of relevance for tissue engineering are starting to
emerge. A recent study has shown the development of
carbon nanofiber (CNF)/NBG composites for bone
regeneration by a combination of electrospinning and
solgel techniques.111 The presence of NBG particles is
usually required to promote the formation of apatite
and to enhance cell proliferation. The developed CNF/
BG composites have great potential for use as substrates
for cell culture or as a reinforcement agent for other
polymeric biomaterials.
10 International Journal of Applied Glass Science—Erol-Taygun, Zheng, and Boccaccini

(a) (b)

(c) (d)

(e)

(f)

Fig. 4. Results of the in vivo study of Hafezi et al.100 on nanosized bioactive glass/gelatin scaffolds. (a) Radiograph of the defect
immediately after surgery showing the removal of the segment of ulna and the creation of a segmental defect in the ulna, (b–e) typical
radiographs of the defect site at 2 weeks (b), 4 weeks (c), 6 weeks (d), 8 weeks (e), and 10 weeks (f) postoperation in the group (a)
(Reproduced with permission of Springer).

Conclusions providing new opportunities for expanding BG applica-

tions in the biomedical field. Nanoscale particulate and
Bioactive glasses in different compositions have nanofiber bioactive glasses have shown advantages over
been widely investigated over the last 40 years; how- conventional (micrometer-sized) bioactive glasses due to
ever, recently developed nanoscaled bioactive glasses are their large surface area and enhanced solubility as well
www.ceramics.org/IJAGS Nanoscale Bioactive Glasses in Medical Applications
as reactivity coupled with the possibility to induce na-
notopographic surface features in composite materials.
The investigations reviewed in the present article indi-
cate the expected advantages of nanoscale bioactive
glasses compared with conventional (lm-scale) bioactive
glasses in particular, for dentistry, orthopedic coatings,
bone tissue engineering, antibacterial materials, and
drug delivery systems. The great potential of nanomet-
ric bioactive glasses is emerging as a powerful approach
toward 3rd generation bioactive materials with the inte-
gration of extended biological effects, such as antioxida-
tive and anticancer functions, where nanoscaled
bioactive glasses can be proposed as key components
for novel devices for nanomedicine. However, to sup-
port further biomaterial developments based on nano-
scale bioactive glasses, greater understanding of the
biological properties of nanoscaled bioactive glasses at
cellular and molecular levels is required, which includes
also the need for substantial long-term in vivo studies,
to enable their safe exploitation in current and new
biomedical applications.
Acknowledgment
KZ acknowledges a scholarship of the China Scho-
larship Council. ARB acknowledges support from the
Emerging Fields Initiative project (TOPbiomat) of the
University of Erlangen-Nuremberg.
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