Silica-chitosan hybrid coating on Ti for controlled release of growth factors.
ABSTRACT A hybrid material composed of a silica xerogel and chitosan was coated on Ti for the delivery of growth-factors. Fibroblast growth factor (FGF) and green fluorescence protein were incorporated into the coatings for hard tissue engineering. Silica was chosen as a coating material because of its high surface area as well as its good bioactivity. Chitosan provides mechanical stability and contributes to the control of the release rate of the growth factors. When the chitosan composition was 30% or more, the hybrid coating was stable physically and mechanically. The release of the growth-factors, observed in phosphate buffer solution at 37°C, was strongly dependent on the coating material. The hybrid coating containing FGF showed significantly improved osteoblast cell responses compared to the pure xerogel coating with FGF or the hybrid coating without FGF. These results indicate that the hybrid coating is potentially very useful in enhancing the bioactivity of metallic implants by delivering growth-factors in a controlled manner.
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ABSTRACT: Due to the disadvantages of the current bone autograft and allograft in many clinical condition in which bone regeneration is required in large quantity, engineered biomaterials combined with growth factors, such as bone morphogenetic protein-2 (BMP-2), have been demonstrated to be an effective approach in bone tissue engineering, since they can act both as a scaffold and as a drug delivery system to promote bone repair and regeneration. Recent advantages in the field of engineered scaffolds have been obtained from the investigation of composite scaffolds designed by the combination of bioceramics, especially hydroxyapatite (HA), and biodegradable polymers, such as poly (D,L-lactide-co-glycolide) (PLGA) and chitosan, in order to realize osteoconductive structures that can mimic the natural properties of bone tissue. Herein it is demonstrated that the incorporation of BMP-2 into different composite scaffolds, by encapsulation, absorption or entrapment, could be advantageous in terms of osteoinduction for new bone tissue engineered scaffolds as drug delivery systems and some of them should be further analyzed to optimized the drug release for future therapeutic applications. New design concepts and fabrication techniques represent novel challenges for further investigations about the development of scaffolds as a drug delivery system for bone tissue regeneration.Clinical Cases in Mineral and Bone Metabolism 01/2013; 10(3):155-161.
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ABSTRACT: In this study, a silica xerogel-chitosan hybrid is utilized as a coating material to incorporate bone morphogenic protein-2 (BMP-2) on a porous hydroxyapatite (HA) scaffold for bone tissue engineering. BMP-2 is known as a therapeutic agent for improving bone regeneration and repair. Silica xerogel-chitosan hybrids have been used for the delivery of a growth factor as well as osteoconductive coatings. The biological properties of the hybrid coating incorporated with BMP-2 were evaluated in terms of the BMP-2 release behavior, osteoblastic cellular responses and in vivo performance. BMP-2 was continuously released from the hybrid coating layer on the porous HA scaffold for up to 6 weeks. The hybrid coating containing BMP-2 showed significantly enhanced osteoblastic cell responses in comparison with the hybrid coating and HA substrate. Consequently, new bone formation was significantly increased within the hybrid coating containing BMP-2. These results reveal that the hybrid coating containing BMP-2 has the potential to be used as a bone implant, whose osteogenic properties are promoted by the release of BMP-2 in a controlled manner for a prolonged period of time.Journal of Materials Science Materials in Medicine 01/2013; · 2.14 Impact Factor
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ABSTRACT: Chitosan–silica/CpG oligodeoxynucleotide (ODN) nanohybrids were synthesized to stimulate Toll-like receptor 9-mediated induction of interleukin-6 (IL-6). The chitosan–silica hybrid was first synthesized from a mixture of chitosan and 3-glycidoxypropyl trimethoxysilane under acidic conditions via a sol–gel process, and then used to condense CpG ODN2006x3-PD to yield chitosan–silica/CpG ODN nanohybrids. Scanning electron micros-copy and atomic force microscopy showed that the chitosan–silica/CpG ODN nanohybrids had an elliptic shape with a diameter of 100–200 nm. After soaking in HAc–NaAc buffer solution (pH 5.5), the nanohybrids exhibited sustained release of CpG ODN. When the nanohybrids were separately exposed to 293XL-hTLR9 cells and periph-eral blood mononuclear cells, no significant toxicity was observed. An immunochemical assay for cellular uptake revealed that the nanohybrids were taken up by the cells and located in endolysosomes. An enzyme-linked immunosorbent assay for cytokines indicated that the nanohybrids effectively stimulated the induction of IL-6. Chitosan–silica/CpG ODN nanohybrids underwent cellular uptake and enhanced induction of IL-6 to a greater degree than conventional chitosan/CpG ODN nanocomplexes, indicating that they have an enhanced delivery efficiency.Materials Science and Engineering C 04/2013; 33(6):3382. · 2.40 Impact Factor
Silica-chitosan hybrid coating on Ti for controlled release
of growth factors
Shin-Hee Jun•Eun-Jung Lee•Hyoun-Ee Kim•
Jun-Hyeog Jang•Young-Hag Koh
Received: 6 January 2011/Accepted: 4 October 2011/Published online: 16 October 2011
? Springer Science+Business Media, LLC 2011
and chitosan was coated on Ti for the delivery of growth-
factors. Fibroblast growth factor (FGF) and green fluores-
cence protein were incorporated into the coatings for hard
tissue engineering. Silica was chosen as a coating material
because of its high surface area as well as its good bioac-
tivity. Chitosan provides mechanical stability and contrib-
utes to the control of the release rate of the growth factors.
When the chitosan composition was 30% or more, the
hybrid coating was stable physically and mechanically. The
release of the growth-factors, observed in phosphate buffer
solution at 37?C, was strongly dependent on the coating
material. The hybrid coating containing FGF showed sig-
nificantly improved osteoblast cell responses compared to
the pure xerogel coating with FGF or the hybrid coating
without FGF. These results indicate that the hybrid coating
is potentially very useful in enhancing the bioactivity of
metallic implants by delivering growth-factors in a con-
A hybrid material composed of a silica xerogel
Various metallic implants have been employed to recon-
struct impaired human tissues in the orthopaedic and dental
fields because of their excellent mechanical properties. The
bioactivity of metallic implants is often improved by sur-
face treatments, especially through surface coating with
osteoconductive substances. Inorganic substances, such as
silica-based glasses or calcium phosphate compounds, have
been widely used as the coating materials on the surface of
metallic implants because of their excellent osteogenic
cellular responses [1, 2].
Recently, there have been many attempts to further
enhance the performance of osteoconductive coatings
through the use of growth factors. Growth factors,
including bone morphogenic protein (BMP), transforming
growth factor-b (TGF-b) and fibroblast growth factor
(FGF), have the advantage of enhancing the efficacy and
safety of the procedure used for the regeneration of the
surrounding bone tissue. Many studies have demonstrated
significant improvements in the osteoconductivity of
implant materials through the use of growth-factors in
combination with coating substances [1–7]. However, it is
difficult to incorporate growth factors into inorganic coat-
ing materials, because coating processes generally require
high-temperature heat treatment which would denature the
In this respect, silica xerogels are attractive coating
materials for use in combination with growth-factors, since
they are synthesized at room-temperature using the sol–gel
process. Silica xerogels have high porosity, nanostructured
pores and bioresorbability. In addition, the sol–gel pro-
cessing allows for the uniform distribution of the growth-
factor in the silica xerogel. However, silica xerogels have
some disadvantages when it comes to utilizing them as
S.-H. Jun ? E.-J. Lee ? H.-E. Kim (&)
WCU Hybrid Materials Program, Department of Materials
Science and Engineering, Seoul National University,
Seoul 151-744, Korea
Department of Biochemistry, School of Medicine,
Inha University, Incheon 400-713, Korea
Department of Dental Laboratory Science and Engineering,
Korea University, Seoul 136-703, Korea
J Mater Sci: Mater Med (2011) 22:2757–2764
coating materials on metallic substances, due to their
brittleness and the initial rapid release of the growth-factors
Chitosan has been widely studied for biomedical
applications due to its biological compatibility and degra-
dability. It is also suitable as a coating material because it is
easily formed into thin layers as well as spheres, fibers and
porous scaffolds. Therefore, in this study, chitosan was
hybridized with silica xerogel for use as a coating layer, in
order to control the release behavior of growth-factors
and improve the physical stability of the coating layers
A hybrid sol of silica with 30% chitosan was prepared
and then growth factors were added to the sol to incorpo-
rate them during the synthesis of the coating layer in an in
situ manner. As the model growth factor, fibroblast growth
factor 2 (FGF 2) (22 kDa), which is known to stimulate
osteoblast cell proliferation and migration, was used [18–
21]. Green fluorescent protein (GFP) (27–30 kDa) was also
used to visualize the incorporation and release behaviors of
the growth factor from the coating layers [22, 23].
2 Materials and methods
2.1 Synthesis of hybrid sols with b-FGF
Tetramethylorthosilane (TMOS, Sigma-Aldrich Chem.
Co., USA), CaCl2, and triethyl phosphate (Sigma-Aldrich
Chem. Co., USA) were chosen as the precursors of the
silica sol containing Ca and P (15 and 5 wt%, respec-
tively), which was synthesized in distilled water using HCl
as a catalyst . 2 g of chitosan powder (85% deacety-
lated, Sigma-Aldrich Chem. Co., USA) was dissolved in
100 ml of 2 wt% acetic acid. The silica sol was mixed with
the chitosan solution (30 vol% chitosan) and the mixtures
were stirred for 10 min. After the hybrids were prepared,
100 lg/ml of FGF or GFP was added to the sols in situ and
the mixtures were stirred for 1 h. The growth-factors were
produced by Escherichia coli (more than 95% purity) fol-
lowing the established procedure [25, 26]. The FGF and
GFP, which were recombinant histidine-tagged (His-tag-
ged, located at the amino-terminal end of the protein)
fusion growth factors, were verified by western blot anal-
ysis by using anti-His polyclonal antibodies (Santa Cruz
Biotechnology, Inc, USA).
NaOH treated titanium (20 9 20 9 2 mm for the dif-
ferentiation tests or 10 9 10 9 1 mm for the other tests)
was used as a substrate, as described elsewhere . 200
and 80 ll of the prepared hybrid sols were spin-coated on
the substrates at 3,000 rpm for 1 min (WS-400-6NPP-
LITE spinner, Laurell Technologies, North Wales, PA) and
then dried at 37?C in a humid atmosphere. The hybrid
coatings were treated with 0.1 N NaOH and then washed
with distilled water and phosphate buffer solution (PBS)
(pH 7.4) to remove the residual acetic acid.
The cross-section and surface morphologies of the
coatings were observed by scanning electron microscopy
(SEM) (JSM 5600, JEOL, Tokyo, Japan). The specimens
for cross-sectional observation were obtained by fracturing
them in liquid nitrogen.
2.2 Release of growth-factors in vitro
The GFP and FGF loaded hybrid coatings (10 9 10 9
1 mm) were immersed in 2 ml of PBS at 37?C and pH 7.4
for 28 and 35 days, respectively. The solutions were
exchanged at specific intervals ranging from 1 day (initial
1 week) to 2–3 days (8–35 days).
The surfaces of the GFP loaded hybrid coatings after the
GFP was released from them in PBS for 0, 14 and 28 days
were observed by confocal laser scanning spectroscopy
(CLSM). The green intensities of the GFP from the hybrid
coatings were measured (n = 3).
The amounts of FGF released were measured by UV-
spectroscopy (ICP-AES, Optima-4300 DV, USA) at
220 nm. A calibration curve was obtained by measuring
the optical absorbance of FGF dissolved in PBS with
concentrations in the range of 0.010–10 lg/ml. The curve
has a linear relationship of FGF concentration (y) =
6.5142 9 optical absorbance (x) – 0.1346 (lg ml-1). By
means of this relationship, each absorbance value was
directly converted to the amount of FGF released. The rel-
ative amounts of FGF released were normalized to that in
the initially loaded coating layer (n = 6).
2.3 Biological properties
The in vitro cellular responses of the in situ FGF loaded
hybrid coatings were evaluated using pre-osteoblast cells
(MC3T3-E1; ATCC, CRL-2593; Rockville, MD) and
compared to those of the hybrid coatings without FGF.
Prior to seeding the cells, the specimens were sterilized by
ultraviolet irradiation for 30 min. The cells were grown in
a-modified minimum essential medium (a-MEM; Wel-
gene, Korea) containing 1% Fetal Bovine Serum (FBS) and
1% antibiotics (100 U ml-1penicillin and 100 lg ml-1
streptomycin; FBS; GIBCO, Grand Island, NY) for 2 days
before the examination of the cellular responses. The cells
were seeded on the samples at a density of 50,000 cells/ml
for initial cell attachment, 30,000 cells/ml for cell prolif-
eration and 20,000 cells/ml for cell differentiation. The
cells were cultured in a culture medium containing 3% FBS
and 1% antibiotics at 37?C in a humidified atmosphere
incubator with 5% CO2.
2758J Mater Sci: Mater Med (2011) 22:2757–2764
The morphology of the cells adhered to the coatings
after 2 h of culture was investigated by CLSM. The cells
on the hybrid coatings with and without FGF were fixed in
4% paraformaldehyde in PBS, permeabilized with 0.1%
Triton X-100 in PBS, and stained with fluorescent
The cell viability was examined using a cell prolifera-
tion assay kit (Cell Titer 96?Aqueous One Solution,
USA). After harvesting the cells on the specimens for
5 days, the hybrid coatings were moved to 700 ll of
medium in a new 24-well plate and 70 ll of MTS solution
was added to each well. After incubating them at 37?C
for 2 h, the colorimetric measurement of the samples
was performed using 200 ll aliquots of each solution by
The cell differentiation of the samples was evaluated
using the alkaline phosphatase (ALP) activity test. After
culturing the cells for 10 days, the cells on the samples
were detached by trypsinization and washed with PBS by
centrifugation at 1,500 rpm for 3 min. The cell pellets were
resuspended in 0.1% Triton X-100 and treated using a
cyclical freezing and thawing process. The ALP activity
levels of the samples were assessed by the detection of
p-nitrophenol (pNP) in the presence of ALP from a
p-nitrophenyl phosphate (pNPP) substrate using a Sigma
Kit 104 commercial kit. The absorbance was measured at
405 nm using a micro-reader and the ALP activity levels
were calculated from a standard curve after normalizing to
the total protein contents.
All experiments involving the in vitro test were repeated
2–3 times. The data are represented as means ±1 standard
error deviation (SED) of triplicate samples (n = 3). Sta-
tistical differences were analyzed using one-way analysis
of variance (ANOVA) with the statistical significance set at
at 490 nmona
The GFP and FGF used in this experiment expressed strong
single bands at 30 and 22 kDa, respectively, by western
blot analysis, as presented in Fig. 1. No other bands were
observed, thus confirming the absence of any other proteins
in the solution of the growth-factor.
The cross-section and surface morphology of the hybrid
coatings with the growth factors on the Ti substrates were
observed by SEM. When the pure silica xerogel was coated
on the Ti substrate, the coating layer was severely cracked
after drying, as shown in Fig. 2a. With the addition of
chitosan to the xerogel, the formation of cracks in the
coating layer became less severe. When 30% or more of
chitosan was added to form the hybrid coating layer, no
cracks were formed, as shown in Fig. 2b. The cross-sec-
tional view of the hybrid coating layer also demonstrated
that it was dense without any defects, as shown in Fig. 2c.
GFP was loaded onto the coating layers and its release
behavior in PBS was monitored by CLSM. When the same
amount of GFP was loaded onto the pure xerogel and the
hybrid coating layers, the intensities of the green fluores-
cence were about the same, as shown in Fig. 3. However,
after 14 days of immersion in PBS, the green fluorescence
observed from the pure xerogel coated specimen was sig-
nificantly lower than that observed from the hybrid coated
specimen. After 28 days of immersion, there was still a
trace of green fluorescence from the hybrid coated speci-
men, while none was observed from the xerogel coated
The intensity of the green fluorescence observed from
the specimens immersed in PBS solution is quantified in
Fig. 4. The intensity from the hybrid coated specimen
decreased steadily, while that from the xerogel coated
specimen decreased rapidly.
The release of FGF in PBS was observed for up to
35 days. Similar amounts of FGF were loaded onto the
pure xerogel and hybrid coatings (1.99 lg for pure xerogel
and 2.03 lg for hybrid coating). The cumulative amounts
of FGF released from the coatings were measured as a
function of the release time, as shown in Fig. 5a. FGF was
released rapidly from the pure silica xerogel coating during
the initial 7 days and then slowly thereafter. After 28 days,
little FGF was released. On the other hand, the release of
FGF from the hybrid coating was relatively steady, so that
appreciable amounts of FGF were released even after
28 days. The steady release of FGF from the hybrid coating
compared to the pure xerogel coating was well illustrated
by the estimated release rates, as shown in Fig. 5b.
Fig. 1 Expression image of the GFP and FGF by western blot
J Mater Sci: Mater Med (2011) 22:2757–2764 2759
The stability of the coating layers in aqueous solution
was estimated by observing the morphology of the coatings
immersed in PBS solution. When the pure xerogel coating
was soaked in PBS at 37?C for 28 days, most of the coating
layer was dissolved away, thus exposing the titanium
substrate, as shown in Fig. 6a. On the other hand, the
surface of the hybrid coated specimen changed only
slightly (Fig. 6b).
The in vitro cellular responses to the FGF loaded coat-
ings were examined in terms of the initial attachment,
proliferation and differentiation levels of osteoblast cells.
Figure 7 shows the CLSM images of the MC3T3-El cells
adhering to the coatings after culturing for 2 h. On the
specimen coated with pure xerogel containing FGF, the
cells adhered well, as shown in Fig. 7a. The cells adhered
and spread even better on the specimen coated with the
hybrid containing FGF (Fig. 7b). For the purpose of com-
parison, a specimen coated with the hybrid, but without
FGF, was also tested. As shown in Fig. 7c, the cells
adhered well on the coated surface, but not as well as on
the specimen containing FGF.
The cell viability, quantified by the MTS assay after
culturing for 5 days, and the differentiation levels, esti-
mated by measuring the ALP activity after culturing for
10 days (n = 3), are illustrated in Fig. 8. The cell viability
was influenced very little by the coating layer when FGF
was included. However, the ALP activity of the cells on the
specimens coated with the hybrid containing FGF was
significantly higher than that on the specimens coated with
the pure xerogel containing FGF, as shown in Fig. 8. When
FGF was not used in the hybrid coating layer, both the cell
viability and ALP activity were lower than those of the
hybrid coating with FGF.
The use of osteoconductive coatings consisting of growth
factors on metallic implants is one of the major issues in
hard tissue engineering for effective bone regeneration.
Therefore, there is a need to develop a delivery vehicle for
the growth factors that would allow for their controlled and
sustained release [1–4, 28]. Silica xerogels are known to
have the potential to be used as drug or growth-factor
delivery vehicles. However, the burst effect resulting from
their instability in aqueous solution is one of the most
serious obstacles to their use in practical applications. In
the present study, a hybrid coating layer consisting of a
silica xerogel and chitosan was developed and its capability
of delivering growth factors (FGF and GFP) was evaluated.
The silica xerogel/chitosan hybrid was synthesized by a
sol–gel method at ambient temperature. A low processing
temperature has the advantages of allowing for the easy
hybridization of the organic materials and growth factors
without the denaturation of the latter. When the hybrid
containing 30% or more of chitosan was used as the
coating material, the coating layer was uniform and free of
cracks, while the pure silica xerogel coating layer was
severely cracked, as shown in Fig. 2. The stability of the
hybrid is attributed to the increase in strength and the
reduction of the shrinkage rate during the drying process as
a result of the addition of chitosan to the silica xerogel.
The hybridization of the silica xerogel and chitosan was
an effective method of fabricating physically stable coat-
ings, which was in turn very useful for controlling the
Fig. 2 SEM micrographs of growth-factor loaded a pure xerogel,
b silica xerogel/chitosan hybrid coating and c typical cross-section
view of the hybrid coating
2760 J Mater Sci: Mater Med (2011) 22:2757–2764
release behavior of the growth factors. Silica xerogels
synthesized by the sol–gel process are known to act as
carriers for growth factors due to their nano-porous struc-
ture. The release behaviors of the growth factors from the
silica xerogel are controlled by the diffusion mechanism,
which explains their rapid initial release [12, 29–31]. On
the other hand, some studies reported that the silica xerogel
coatings had a different nanostructure from that of the bulk
materials. The sol–gel transformation of silica overlaps
with and occurs immediately during the formation of the
coating layer, so that the silica xerogel coating has a lower
porosity than that of the bulk xerogel. Due to its less porous
structure, the penetration of the solution used for the
Fig. 3 Typical CLSM images
of GFP loaded pure xerogel and
the hybrid coatings after GFP
was released from them for up
to 28 days
Fig. 4 The integrated green intensity of the GFP loaded pure xerogel
and hybrid coatings as a function of the release time in PBS solution
(n = 3)
Fig. 5 a Cumulative amounts of FGF released from pure xerogel and
hybrid coatings as a function of time in PBS solution and b the
differentials of the amount of FGF released (n = 6)
J Mater Sci: Mater Med (2011) 22:2757–27642761
release of the growth factor is hindered and the diffusion of
the growth factor is limited compared to that of other forms
of silica xerogels [10, 12, 17, 32, 33]. In this study, the GFP
was released from the xerogel coating layer rapidly in the
early stage and then slowly after about 14 days (Fig. 4). On
the other hand, the coatings hybridized with 30% of
chitosan showed a steady release of GFP for a longer
period of time. In addition, it is of note that the GFP release
data from the hybrid coating had much smaller standard
deviations compared to those from the pure xerogel
coating. This discrepancy is deemed to be closely related to
the physical stability of the coating layers.
A similar trend was observed for the FGF release
behavior. The FGF was released quickly from the pure
xerogel coating layer in the early stage and then slowly
after about 7 days. The FGF from the hybrid coating was
released relatively steadily, so that it was still being
released even after 35 days. The stability of the coating
layer is also reflected in the morphology of the coatings
after the release tests. As shown in Fig. 6a, the pure xerogel
coating was severely damaged after being immersed in
PBS for 28 days. On the other hand, the surface mor-
phology of the hybrid coating was changed very little, as
shown in Fig. 6b, and the green fluorescence of the hybrid
coating with GFP was still observed after the same period
of time (Fig. 3). These results indicate that the steady
release of the growth factors from the hybrid coating is
attributable to the enhanced stability of the xerogel con-
taining chitosan. Besides, it is considered that the incor-
porated growth factors retain their properties without any
denaturation after the growth factor has been released for a
long period of time.
Fig. 6 SEM micrographs of growth-factor released from a pure
xerogel and b hybrid coatings after 28 days immersion in PBS
Fig. 7 CLSM images of cellular attachment of a the pure xerogel coating with FGF and the silica xerogel-chitosan (70/30) hybrid coating b with
and c without FGF after culturing for 2 h
Fig. 8 Cell proliferation level and ALP activity level of MC3T3-E1
cells of pure xerogel coating with FGF, hybrid coating with FGF and
the hybrid coating without FGF
2762 J Mater Sci: Mater Med (2011) 22:2757–2764
FGF, an osteostimulative factor, is known to improve the
bone healing process and the demineralization of the bone
matrix by promoting the proliferation of the cells [18–21,
34, 35]. Especially, FGF-2 is a single-chain polypeptide
which acts as a mitogen and chemoattractant for various
cells; as a result, it plays a key role in angiogenesis and the
bone formation process. Previous studies have also reported
that a high bone formation rate is associated with early
angiogenesis . Both the coating layers (pure xerogel and
hybrid) containing FGF showed excellent in vitro cell
responses. The osteoblastic cells attached and spread well
on the coating layers with FGF, as shown in Fig. 7a, b. Even
without FGF, the cells attached well on the hybrid coating
layer (Fig. 7c), indicating the good bioactivity of the silica
xerogel-chitosan hybrid [26, 37]. The effects of the coating
material and FGF on the proliferation and differentiation of
the osteoblastic cells were estimated by observing the cell
viability and ALP activity, respectively. The cell viability
after culturing for 5 days was not influenced very much by
the coating material when FGF was included in the coating
layer, as shown in Fig. 8. However, the ALP activity of the
cells cultured for 10 days on the hybrid coating layer with
FGF was significantly higher (P\0.05) than that on the
xerogel coating layer with FGF for the same period of time.
The beneficial effect of the steady release of the growth
factors on the osteoblastic cells was well illustrated by this
ALP activity. Therefore, it is clear that the incorporation of
FGF further enhanced the bioactivity of the silica xerogel-
chitosan hybrid coating layer.
The silica xerogel/chitosan hybrid was used as a coating
material for delivering growth-factors to enhance the bio-
activity of Ti. The growth factors (GFP and FGF) were
incorporated into the coating layer during the coating
process at ambient temperature. The coating layer was
uniform and physically stable when 30% or more of
chitosan was contained in the hybrid. The growth factors
were distributed homogeneously in the coatings and were
released for a long period of time (*30 days) from both of
the coating layers. However, the growth factors were
released more steadily from the hybrid coating layer. The
in vitro cellular bioactivity of the hybrid coating with FGF
was higher than that of the pure xerogel coating with FGF,
because of this steady release of the growth factor.
Class University) project through National Research Foundation of
Korea funded by the Ministry of Education, Science and Technology
(R31-2008-000-10075-0) and by the Fundamental R&D Program for
Core Technology of Materials funded by the Ministry of Knowledge
Economy, Republic of Korea.
This research was supported by WCU (World
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