Hydroxyapatite poli


ARTICLE IN PRESS
Biomaterials 25 (2004) 1279 1287
Hydroxyapatite/poly(e-caprolactone) composite coatings on
hydroxyapatite porous bone scaffold for drug delivery
Hae-Won Kima,b,*, Jonathan C. Knowlesa, Hyoun-Ee Kimb
a
Eastman Dental Institute, Biomaterials and Tissue Engineering, University College London, 256 Gray s Inn Road, London WC1X 8LD, UK
b
School of Materials Science and Engineering, Seoul National University, Seoul, 151-742, South Korea
Received 3 June 2003; accepted 1 August 2003
Abstract
Hydroxyapatite (HA) porous scaffold was coated with HA and polycaprolactone (PCL) composites, and antibiotic drug
tetracycline hydrochloride was entrapped within the coating layer. The HA scaffold obtained by a polymeric reticulate method,
possessed high porosity (B87%) and controlled pore size (150 200 mm). Sucha well-developed porous structure facilitated usage in
a drug delivery system due to its high surface area and blood circulation efficiency. The PCL polymer, as a coating component, was
used to improve the brittleness and low strength of the HA scaffold, as well to effectively entrap the drug. To improve the
osteoconductivity and bioactivity of the coating layer, HA powder was hybridized with PCL solution to make the HA PCL
composite coating. With alteration in the coating concentration and HA/PCL ratio, the morphology, mechanical properties, and
biodegradation behavior were investigated. Increasing the concentration rendered the stems thicker and some pores to be clogged; as
well increasing the HA/PCL ratio made the coating surface be rough due to the large amount of HA particles. However, for all
concentrations and compositions, uniform coatings were formed, i.e., with the HA particles being dispersed homogeneously in the
PCL sheet. With the composite coating, the mechanical properties, such as compressive strength and elastic modulus were improved
by several orders of magnitude. These improvements were more significant with thicker coatings, while little difference was observed
with the HA/PCL ratio. The in vitro biodegradation of the composite coatings in the phosphate buffered saline solution increased
linearly with incubation time and the rate differed with the coating concentration and the HA/PCL ratio; the higher concentration
and HA amount caused the increased biodegradation. At short period (o2 h), about 20 30% drug was released especially due to
free drug at the coating surface. However, the release rate was sustained for prolonged periods and was highly dependent on the
degree of coating dissolution, suggesting the possibility of a controlled drug release in the porous scaffold with HA+PCL coating.
r 2003 Elsevier Ltd. All rights reserved.
Keywords: Hydroxyapatite (HA); Poly(e-caprolactone) (PCL); Porous bone scaffold; Composite coating; Drug release; Mechanical properties
1. Introduction to encapsulate drugs, such as biodegradable polymers
(synthetic or natural) and bioactive ceramics, in the
Drug delivery systems (DDS) have been developed to form of particulates, membranes, and porous matrix [5
enhance bone ingrowth and regeneration in the treat- 10]. Among those, hydroxyapatite (HA) has enhanced
ment of bone defects [1 4]. Because of the poor blood interest as a drug delivery carrier due to its osteocon-
circulation in the osseous defect sites, a level of drugs, ductivity and biocompatibility [10 14].
such as antibiotics, antimicrobials, and growth factors, Practically, the HA porous forms have been used as
need to be supplied to the affected regions [4,5]. In order bone scaffolds to prove an improved bone ingrowthand
to be effective as a DDS, the carrier needs to fulfill the osseointegration [15 17]. However, the brittleness and
requirements of safety, greater efficacy, predictable low strength limited their wider applications in hard
therapeutic response, and controlled and prolonged tissue implants [18 22]. To be used effectively in load
release period [1,4]. Several carriers have been developed bearing compartments, the mechanical properties of the
HA porous body should be improved. Moreover, as a
DDS, the pore structure of the scaffold needs to be
*Corresponding author. Tel.: +44-(0)20-7915-1090; fax: +44-(0)20-
controlled in terms of porosity and pore size [10,15,16].
7915-1227.
E-mail address: hkim@eastman.ucl.ac.uk (H.-W. Kim). More importantly, drugs should be entrapped efficiently
0142-9612/$ - see front matter r 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.biomaterials.2003.07.003
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1280 H.-W. Kim et al. / Biomaterials 25 (2004) 1279 1287
to be released for a prolonged period [4]. In order to slurry uniformly throughout the porous scaffolds with-
optimize these requirements, coating design of the out blocking the pores, the sponge was dried at 80 C for
porous scaffold was proposed. By coating with plastic 12 h. These dipping-and-drying steps were repeated
polymer layer, the brittleness of the porous scaffold is twice. The obtained body was heat-treated to burn out
expected to be overcome. Moreover, drugs may be the sponge and binder at 600 C for 3 h at a heating rate
efficiently entrapped through the scaffold by being of 1 C/min, and at 1300 C for 3 h to solidify. The
coupled with polymer. In order to improve the coating-and-heat treating processes were repeated twice.
biocompatibility of the polymer, HA powder was
hybridized with the polymer. Practically, the HA
2.2. HA PCL composite coatings entrapped with drug
powders have been hybridized with biological polymers,
TCH
suchas PLGA, PMMA, and polycaprolactone (PCL) in
the form of films and microspheres [23 26]. The PCL
Firstly, composite solutions for coating were prepared
was attractive due to its low cost, sustained biodegrad-
from poly(e-caprolactone) pellets (PCL; 
ability, and availability at low molecular weight [27 29].
[(CH2)5COO]n , Mw=80,000, Sigma-Aldrich, UK)
In this study, we fabricated HA porous scaffolds by a
and HA powders. Various amounts (1.25, 2.5, 3.75%
polymeric reticulate method and coated them with HA
w/v) of PCL were dissolved in dichloromethane (DCM;
PCL composites after being entrapped withan antibiotic
CH2Cl2, Sigma-Aldrich, UK) by stirring for 6 h at room
drug tetracycline hydrochloride (TCH). The morpholo-
temperature. Preset amounts of HA powder (HA/
gical change, mechanical properties, and biological
PCL=0.25, 1, and 4 w/w) were added to the PCL
degradation behaviors of the coating scaffolds were
solution and stirred for 24 h. A fixed concentration
investigated. Moreover, the in vitro drug release was
[TCH/(HA+PCL)=0.1 w/w] of antibiotic drug TCH;
examined in correlation with the biodegradation of the
C22H24N2O8 HCl (Sigma-Aldrich, UK) were added to
scaffolds.
the solution and stirred for 24 h.
The prepared HA scaffolds were dipped into the
composite solutions and then rotated for 5 s to remove
2. Materials and methods
the excess solution and to form a uniform coating. The
coated scaffolds were dried for 48 hand kept for further
2.1. Fabrication of HA porous scaffold
tests. The composition and designation of the coatings
were summarized in Table 1.
The HA porous scaffold was made by a polyurethane
foam reticulate method [18]. The coating slurry was
prepared from a commercial HA powder (Sintering 2.3. Characterization and drug entrapment determination
grade, Plasma Biotal Ltd., UK). The powder was used
after calcination at 900 C for 3 h. The powder of 50 g The porosity of the scaffolds was calculated by
was stirred vigorously in 100 ml distilled water after measuring their dimension and weight. The average
being dispersed with a triethyl phosphate (TEP; pore size was calculated from pictures taken from
(C2H5O)3PO, Sigma-Aldrich, UK) of 5 g for 6 h. As a scanning electron microscopy (SEM; Stereoscan S90,
binder, poly vinyl butyl (PVB, Sigma-Aldrich, UK) of Cambridge Ltd., UK) by selecting five arbitrary areas.
5 g was dissolved in another beaker for 3 h, which was In order to observe the phase and structure the coating
subsequently added to the slurry and stirred for an layer, composite solutions were poured into a glass Petri
additional 24 h. dish to form a coating thickness of B200 mm, and then
Polyurethane foam templates (Customs Foam Ltd., each film was characterized with X-ray diffraction
UK) cut to appropriate dimensions were immersed in (XRD; Philips, PW4620, Holland) patterns and Four-
the slurry. After blowing with an air gun to disperse the ier-transform infrared (FT-IR; System 2000, Perkin-
Table 1
Compositions and designations of the composite coatings
Designation Composition (w/v%) Ratio
HA PCL TCH Total (HA+PCL+TCH) HA/PCL TCH/(HA+PCL)
HPT1 1.25 1.25 0.25 2.75 1 0.1
HPT2 2.5 2.5 0.5 5.5 1 0.1
HPT3 3.75 3.75 0.75 8.25 1 0.1
HPT2-1 1 4 0.5 5.5 0.25 0.1
HPT2-2 4 1 0.5 5.5 4 0.1
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H.-W. Kim et al. / Biomaterials 25 (2004) 1279 1287 1281
Elmer, USA) spectroscopy. The coating morphology on particles impregnated into the PCL, covered the HA
the porous structure was evaluated using SEM. framework partially (Fig. 1(D)). Some of the HA
The weight change of the porous scaffolds before and powders were in the form of clusters with sizes of B1
after coating was measured using an electronic balance 3 mm. The TCH, which could not be discerned separately
(Analytical Balance, BDH, USA) with a sensitivity of from the coating layer, might be adherent to the HA
5 10 6 g. The drug TCH entrapment was determined powders or dispersed into the PCL film. When the
from the total weight change considering the initial drug coating concentration increased (HPT2), the scaffold
ratio (TCH/HA+PCL=0.1). structure changed somewhat; the stems became thicker
and some pores were partially closed (Fig. 1(E)). The
2.4. Mechanical test coating layer covered the surface to a high degree, while
remaining bubble-like pores, and the HA powders were
The porous scaffolds with a dimension of dispersed uniformly within the coating film (Fig. 1(F)).
B10 10 5mm3 were used for a compression test At much higher concentration (HPT3), the stem became
using Instron (Model: 4505, UK) by applying load via much thicker and some pores were fully clogged (Fig.
1 n load cell at a crosshead speed of 2 mm/min in 1(G)). The coating layer covered the surface nearly
ambient conditions. The stress strain curve obtained completely, forming a relatively dense film with HA
was used to determine mechanical properties. The particles surrounded by PCL sheet (Fig. 1(H)). The
compressive strength and elastic modulus was deter- coating morphologies obtained with different HA/PCL
mined from the maximum load recorded and from the ratios are shown in Figs. 1(I) and (J). The
slope at the initial stage (o 2% strain), respectively. HA+PCL+TCH amount was the same as that of
Four specimens were tested for each condition. HPT2. In the coating with low HA/PCL ratio (HA/
PCL=0.25, HPT2-1), the HA clusters were barely
2.5. Biodegradation and drug release observed (Fig. 1(I)). In contrast, higher HA/PCL ratio
(HA/PCL=4, HPT2-2) changed the coating structure to
The coated scaffolds, having similar weight and be highly rough, which was attributed to existence of
dimension of approximately 0.8 1 g and 20 20 lots of HA particles. However, the HA particles were
6mm3, respectively, were immersed into a glass bottle firmly stuck to the scaffold due to the presence of PCL;
containing 100 ml phosphate buffered saline (PBS; even at small amounts, the PCL played a role in binding
Sigma-Aldrich, UK) medium under 37 C at pH 7.4 the HA particles together.
for periods up to 7 days. At predetermined periods of
time, the samples were taken out and vacuum dried for 3.2. Drug entrapment
24 h. The dried samples were weighed to determine the
biodegradation rate. The medium was refreshed at each As presented in the SEM morphologies, the loading
test period. The drug (TCH) release amount was amounts of the coatings differed depending on the
measured using an UV spectrophotometer (Unicam coating conditions. Table 2 shows the weight changes of
UV500, ThermoSpectronic, UK) at a wavelength of the coating scaffolds during the coating process. The
350 nm. weight gain of each coating layer was normalized
to the initial scaffold weight. The weight gain
increased steadily with increasing the concentration
3. Results (HPT3>HPT2>HPT1). Such a fact suggests that the
amount of coating, and further the drug encapsulation
3.1. Morphology can be controlled efficiently by changing the coating
concentration. Although there were ongoing increases in
Fig. 1 shows the typical SEM morphologies of the the weight gain with increasing concentration, little
porous scaffolds before ((A) and (B)) and after coating difference was observed among the coatings with
with HA PCL composites by varying solution concen- different HA/PCL ratio. The drug entrapment within
trations ((C) (H)) and compositions ((I) and (J)). For all the coating was easily calculated from the weight gains
coatings, the TCH was added at 10% with respect to of the coatings, since the drug should be kept within the
HA+PCL. The pure HA scaffold showed a well- composite coating layer. The data will be used as a
developed porous structure, with porosity and pore size reference in the following drug release test.
of approximately 87% and 150 200 mm, respectively
(Figs. 1(A) and (B)). When the scaffold was coated with 3.3. Phase and structure
HA PCL composite at low concentration (HPT1), the
scaffold almost maintained the initial HA framework Fig. 2 shows the XRD patterns of the HA PCL
structure (Fig. 1(C)). At high magnification, the coating composite coatings containing different HA/PCL ratio
layer, consisting of PCL thin sheet (o1 mm) and HA and entrapped with 10% drug. For all compositions,
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(A) (B)
200 µm 10 m
(C) (D)
10 m
200 µm
(E) (F)
200 µm
10 m
(G) (H)
200 m
10 m
(I) (J)
10 m 10 m
Fig. 1. SEM morphologies of the HA porous scaffolds without and with different HA PCL composite coatings entrapped with drug TCH (TCH/
HA+PCL=1). (A,B) pure HA, (C,D) HPT1, (E,F) HPT2, (G,H) HPT3, (I) HPT2-1, and (J) HPT2-2.
typical PCL and HA peaks appeared. There were no the peak intensities of HA and decreased those of PCL
other peaks nor peak shifts in the composites, suggesting correspondingly.
that no chemical reactions occurred. The increase in the The structures of the composite coatings were
HA/PCL ratio (HPT2-2>HPT2>HPT2-1) increased analyzed using FT-IR spectroscopy, as shown in
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H.-W. Kim et al. / Biomaterials 25 (2004) 1279 1287 1283
Table 2
Weight changes in the scaffolds during composite coatings
Weight changes Composite coatings
HPT1 HPT2 HPT3 HPT2-1 HPT2-2
Total weight gain (HA+PCL+TCH)
Measured (mg) 31.0 67.5 97.5 73.5 55.5
(73.8) (74.5) (76.8) (74) (74.2)
Normalized to HA scaffold 3.76 7.79 11.1 8.15 6.35
(70.21) (70.43) (70.52) (70.30) (70.51)
Estimated TCH entrapment (mg) 2.82 6.13 8.86 6.68 5.05
(70.26) (70.52) (70.72) (70.36) (70.38)
Initial drug amount was estimated from the total weight gain of coating considering the TCH to HA+PCL is 0.1.
HPT2-1
C=O
C-O
C=H
HPT2
O-H
P-O
P-O
HPT2-2
1800 1400 1000 600
Wave number [cm-1]
Fig. 2. XRD patterns of the composite coatings entrapped with drug
Fig. 3. FT-IR analyses of the composite coatings entrapped with drug
TCH. Each coating had different HA/PCL ratio (0.25, 1, and 4) and
TCH. Each coating had different HA/PCL ratio (HA/PCL=0.25, 1,
the same total concentration (HA+PCL+CH=5.5% w/v) and drug
and 4) and the same total concentration (HA+PCL+TCH=5.5%
amount (TCH/HA+PCL=0.1). Symbols are ( ) HA and ( ) PCL.
w/v) and drug amount (TCH/HA+PCL=0.1).
Fig. 3. Characteristic structural bands of both HA and was 0.1 with respect to total coating. The mechanical
PCL were observed for all HA/PCL ratios. The C=O, properties of the scaffolds were summarized in Table 3.
C O, and C=H bands corresponded to PCL and the P Compared to pure HA, all the coating samples exhibited
O and O H bands were attributed to HA. The higher compressive strengths. Among the coating speci-
corresponding band intensities increased with their mens, the higher concentration showed the higher
mixing portion increasing. As was in the XRD data, strength (HPT3>HPT2>HPT1) while little difference
no band shifts were observed in the FT-IR spectroscopy, was observed with HA/PCL ratio change (compare
confirming that no chemical reactions occurred among HPT2, HPT2-1, and HPT2-2). The highest strength was
the mixed components. The XRD and FT-IR patterns obtained in the HPT3 coating scaffold (0.45 MPa) and
in other concentrations were similar to those in HPT2. the value was about three times higher than that of pure
HA (0.16 MPa). The elastic modulus behaved in a similar
3.4. Mechanical properties manner to the compressive strength. The highest value
(B2 MPa) obtained in the HPT3, was approximately two
In order to observe the mechanical properties of the times higher than that of the pure HA (B1MPa).
scaffolds, a compressive load was applied to eachsample
of dimensions B10 10 5mm3. Constant load and 3.5. Biodegradation
speed were exerted until the final failure or densification
occurred. Pure HA scaffold was also tested for the The total weight changes of the scaffolds after
purpose of comparison. For all cases, the drug amount dissolving in a phosphate buffered saline (PBS) solution
% Transmittance [Arb.unit]
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Table 3
Mechanical properties of porous scaffolds without and with composite coatings
Mechanical properties Pure HA Composite coatings
HPT1 HPT2 HPT3 HPT2-1 HPT2-2
Compressive strength (MPa) 0.16 0.24 0.32 0.45 0.27 0.3
(70.04) (70.04) (70.03) (70.04) (70.04) (70.03)
Elastic modulus (MPa) 0.79 1.00 1.12 1.43 1.02 1.15
(70.04) (70.02) (70.02) (70.2) (70.2) (70.3)
Table 4
Drug releases from the coating scaffolds after immersion in a PBS solution for 2 h and 7 days at 37 C
Time Drug release Composite coatings
HPT1 HPT2 HPT3 HPT2-1 HPT2-2
2 hApparent amount (mg/ml) 0.011 0.015 0.022 0.015 0.017
Normalized to initial drug (%) 29.7 19.2 19.1 19.7 25.7
7 days Apparent amount (mg/ml) 0.021 0.038 0.049 0.033 0.040
Normalized to initial drug (%) 58.1 47.8 42.5 44.1 60.8
at 37 C for periods up to 7 days are represented with concentration (HPT3>HPT2>HPT1). There was little
respect to incubation time in Fig. 4. For all the coating difference among the samples with different HA/PCL
scaffolds, the weight steadily decreased with incubation ratio.
time. The sample with higher coating concentration The drug release was normalized to the initial drug
showed the higher weight loss, i.e., entrapped in the coatings, and are represented in Fig. 7.
HPT3>HPT2>HPT1. Moreover, the samples contain- Data showed a quite different trend among the coating
ing higher HA amount dissolved more quickly, i.e., samples when compared to Fig. 6. The thinner coating
HPT2-2>HPT2-1>HPT2, suggesting that the HA showed the higher release. Moreover, the HA/PCL ratio
dissolved faster than the PCL did. The HPT2-2, which affected the release considerably; the higher drug release
contained higher HA amount, showed a similar was observed in the higher HA amount. Table 4 shows
dissolution rate to the HPT3 although it has the lower the quantitative drug release amounts after an initial
coating concentration. period (2 h) and after 7 days. Approximately 20 30%
The total weight loss in Fig. 4 was normalized with and 40 60% of the loaded drug were released after 2 h
respect to the initial coating weight, and is represented in and 7 days, respectively, depending on the coating type
Fig. 5. Data showed quite different trends from those in (Table 4). The initial rapid release was higher in the
Fig. 4. The sample coated with low concentration lower concentration and the higher HA/PCL ratio.
showed the higher dissolution behaviors, i.e.,
HPT1>HPT2>HPT3. This was attributed to the
difference in coating thickness and surface morphology, 4. Discussion
in other words, the thicker and more compacted
structure with high concentration resulted in a reduced In this study, the HA porous scaffolds were developed
dissolution. The samples coated with different HA/PCL by a coating design of HA and PCL composites for
ratio showed similar trends as observed in Fig. 4. Th e usage in hard tissue engineering. Moreover, an anti-
HPT2-2 had the highest dissolution rate among the all biotic drug TCH was entrapped to investigate the
samples. efficacy of the scaffolds as DDS. In the coating-scaffold
design, each component has its specific role. Further-
3.6. Drug release more, their combination was pursued to optimize the
biocompatibility of the system. As a carrier, calcium
The drug release amounts were measured using an phosphate, more specifically HA was chosen for its
UV spectrophotometer and are shown in Fig. 6. For all osteoconductivity and bioactivity [2,13 15]. Moreover,
samples, the TCH was released relatively quickly within the HA was fabricated in the form of a porous structure,
short periods and the then release rate slowed with time. providing high specific area, entrapping large amounts
The release amount was highly dependent on the coating of drug, whilst retaining enough space for blood
concentration, i.e. the larger amount in the thicker circulation [15 17]. The high porosity (B87%) and
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H.-W. Kim et al. / Biomaterials 25 (2004) 1279 1287 1285
appropriate pore size (150 200 mm) were sufficient to without fracture and the dissipation of the stress to the
satisfy those requirements [15,16]. neighboring stems. Such a stress-relaxation has been
However, the poor mechanical properties of the HA pursued in ceramic materials to overcome their brittle-
scaffold, especially low strength and brittleness restrict ness. In this study, such was possible only with the
its wide applications [18 22]. The difficulty in handling introduction of the PCL polymer component; the
is the main drawback in a real surgical situation; also the coating with only HA could not show such effective
fragments and debris created have adverse effects on energy absorption although maximum strength could be
complete osseointegration. Moreover, as a drug delivery improved due to thicker stems and porosity reduction
system, the HA scaffold alone seems insufficient to keep [18].
drugs at the site and entrap them, resulting in a drug The dissolution behaviors of the scaffolds were highly
release in an uncontrolled way. In this respect, the HA affected by the coating conditions. The dissolution of
PCL coating on the scaffold was developed, and the the pure HA scaffold was, as expected, negligible when
drug encapsulation was facilitated by means of the compared to the coating samples (Table 4). Among the
coating solution. The PCL coating component is coating scaffolds, the thicker concentration and the
expected to protect the drug since the PCL can dissolve, higher HA ratio resulted in higher dissolution (Fig. 4).
be mixed with drug, and be hardened to form a dense The complete coating coverage throughout the stem
structure. Moreover, the polymer provides flexibility to with the thicker concentration is deemed to contribute
the brittle system. On the other hand, the HA coating to the higher dissolution. However, the normalized data
element was hybridized with the PCL to improve the to initial coating layer showed an opposite trend among
biocompatibility of the polymer. Moreover, being in the the coatings with concentration difference, suggesting
powder form, the HA provides enhanced bioactivity to that larger amount of coating layer remained in the
the HA scaffold framework which was sintered at higher concentration (Fig. 5). Interestingly, the HA
elevated temperature (1300 C). appeared to dissolve more quickly than the PCL did; in
As confirmed by the SEM morphologies, the PCL the order HPT2-2>HPT2>HPT2-1. Regarding the
HA solutions containing TCH were well coated on the role of HA in the biodegradation of the HA polymer
scaffolds by a simple dipping-and-drying method composites, there are conflicting reports: Increasing the
(Fig. 1). The coating morphology and composition were dissolution of HA PCL composite due to the high
well tailored via solution parameters, the solution bioactivity of HA [31]; whilst decreasing the bioresorp-
concentration and HA/PCL ratio. Moreover, the load- tion of the HA PLGA composites due to the water
ing amount changed corresponding to both parameters adsorption of HA [32]. The differences in the HA
(Table 1). Such a control of loading amount is a powder characteristics and polymer types, and the
prerequisite for a controlled drug release. In this system, dissolution media might result in such a discrepancy.
since the drug was safely entrapped within the HA PCL Therefore, a final decision remains for further study. In
coating network and there was no drug loss during the this system, at least, the HA powder played a crucial
coating process, the total loading amount (the total role in determining the dissolution of the composite
weight gain) can be easily converted to give the amount coating.
of the drug entrapment (Table 1).
With the HA PCL coating, all the mechanical
properties of the scaffold changed considerably, and
25 HPT1
the change was more significant with increasing coating
HPT2
concentration. Those trends were well understood when
HPT3
20
HPT2-1
considering not only the change in the scaffold
HPT2-2
morphology with coating but also the mechanical
properties of the coating layer itself. With coating and
15
increasing its concentration, the stems became thicker,
and at high concentration, some pores were even closed
10
(Fig. 1). Those affected the improvement of the
mechanical properties to some extent. Moreover, the
coating layer covering the framework was highly plastic
5
since it contained PCL as well. Practically, a fracture
was initiated at the weakest stem, which containing the
most severe flaws. The coating layer possibly covered or 0
0 50 100 150
blunted the flaws, contributing to the higher strength
Time [h]
and strain to failure [29,30]. Under external load, the
coated framework could distribute stress and absorb
Fig. 4. Weight losses of the coating scaffolds after dissolution test in a
energy more effectively, by the sufficient deformation PBS solution at 37 C for periods up to 7 days.
Total weight Loss [mg]
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1286 H.-W. Kim et al. / Biomaterials 25 (2004) 1279 1287
HPT1
60
HPT2
40
HPT3
HPT2-1
HPT2-2
30
40
20
HPT1
20
HPT2
HPT3
10
HPT2-1
HPT2-2
0
0
050 100 150
0 50 100 150
Time [h]
Time [h]
Fig. 5. Normalized weight losses of the coating scaffolds after
Fig. 7. Normalized drug release amount from the coating scaffolds
dissolution test in a PBS solution at 37 C for periods up to 7 days.
with respect to the initial drug amount after dissolution test in a PBS
Total weight loss (Fig. 4) was normalized with respect to the initial
solution at 37 C for periods up to 7 days. Initial drug amount was
coating amount (Table 2).
taken from Table 2.
Such a fact indicates that the drug release mechanism
0.05 was considerably affected by the coating resorption. In
this respect, the coating conditions, such as concentra-
tion and composition are of paramount importance for
0.04
a controlled drug release. However, the drug release and
coating degradation should be considered in tandem
0.03
with the mechanical behavior since the coating condi-
tion alters bothproperties simultaneously. For example,
the increase in the HA amount, which was aimed to
0.02
increase the coating dissolution and drug release, will
HPT1
decrease the mechanical flexibility of the scaffolds. More
HPT2
0.01
importantly, the appropriate coating compositions (HA/
HPT3
PCL/TCH) should be chosen in consideration of the
HPT2-1
compatible cellular responses. The in vitro cellular test is
HPT2-2
0.00
currently undertaken to evaluate the biocompatibility of
0 50 100 150
the system.
Time [h]
Fig. 6. Drug release amounts from the coating scaffolds after
5. Concluding remarks
dissolution test in a PBS solution at 37 C for periods up to 7 days.
Data were obtained from UV spectrophotometer at wavelength of
350 nm.
The HA PCL composites were effectively coated on
HA porous scaffolds to optimize the biocompatibility of
Compared to the coating dissolution, the drug release the system. As drug delivery usage, the antibiotic TCH
was much faster, especially at short period (Figs. 6 and was entrapped within the composites. Coatings were
7). About 20 30% of drug was released within 2 h. Such obtained by dipping-drying process with varying the
an abrupt release was due to the free drug remaining at concentration and HA/PCL ratio. The loading amount
the surface without entrapped efficiently within the of coatings increased with increasing the concentration
coating layer. Sucha phenomenon is known as an initial and HA/PCL ratio. The composite coatings improved
burst in the microspheres and films [33,34]. However, the mechanical properties of the scaffolds, such as
after an initial burst the drug was released in a sustained compressive strength and elastic modulus. The dissolu-
manner, and the rate decreased for all the coating tion rate of the scaffold was well controlled with the
samples with time. More importantly, after an initial coating conditions, and the rate increased with increas-
burst, the drug release corresponded to the coating ing the concentration and HA/PCL ratio. After a free
dissolution (compare Figs. 4 and 5 with Figs. 6 and 7). drug release within short period (o2 h), the drug was
Normalized drug release [%]
Normalized weight Loss [%]
Drug release [mg/ml]
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H.-W. Kim et al. / Biomaterials 25 (2004) 1279 1287 1287
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Effect of pore size and void fraction on cellular adhesion,
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Porous ZrO2 bone scaffold coated with hydroxyapatite with
This work was supported by the Post-doctoral
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Fellowship Program of Korea Science & Engineering
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