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Polycaprolactone/starch composite: Fabrication, structure, properties, and

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DOI: 10.1002/jbm.a.35371

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Polycaprolactone/starch composite: Fabrication, structure, properties,
and applications

Soheila Ali Akbari Ghavimi,1 Mohammad H. Ebrahimzadeh,2 Mehran Solati-Hashjin,1,3

Noor Azuan Abu Osman1
1
Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, 50603 Kuala Lumpur, Malaysia
2
Orthopedic Research Center, Mashhad University of Medical Science, Mashhad, Iran
3
Department of Biomedical Engineering, Amirkabir University of Technology, 15914 Tehran, Iran

Received 18 August 2014; revised 28 October 2014; accepted 13 November 2014

Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.a.35371

Abstract: Interests in the use of biodegradable polymers as
biomaterials have grown. Among the different polymeric
composites currently available, the blend of starch and poly-
caprolactone (PCL) has received the most attention since the
1980s. Novamont is the first company that manufactured a
PCL/starch (SPCL) composite under the trademark Mater-BiV R.
The properties of PCL (a synthetic, hydrophobic, flexible,
expensive polymer with a low degradation rate) and starch (a
natural, hydrophilic, stiff, abundant polymer with a high deg-
dation rate of PCL. Thus, by appropriate blending, SPCL can
overcome important limitations of both PCL and starch com-
ponents and promote controllable behavior in terms of
mechanical properties and degradation which make it suita-
ble for many biomedical applications. This article reviewed
the different fabrication and modification methods of the
SPCL composite; different properties such as structural, phys-
ical, and chemical as well as degradation behavior; and dif-
ferent applications as biomaterials. V
C 2014 Wiley Periodicals, Inc.

radation rate) blends are interesting because of the compos- J Biomed Mater Res Part A: 00B:000–000, 2014.
ite components have completely different structures and
characteristics. PCL can adjust humidity sensitivity of starch Key Words: polycaprolactone, starch, polymeric composite,
as a biomaterial; while starch can enhance the low biodegra- tissue engineering, degradation

How to cite this article: Ali Akbari Ghavimi S, Ebrahimzadeh MH, Solati-Hashjin M, Abu Osman NA. 2014. Polycaprolactone/
starch composite: Fabrication, structure, properties, and applications. J Biomed Mater Res Part A 2014:00A:000–000.

INTRODUCTION shown that starch is beneficial in drug delivery

Polysaccharides like starch are interesting renewable
resources that have different applications. Indeed, starch is
available in large quantities and is inexpensive because it is
obtained from biomass. Starch is the cheapest biopolymer;
it is renewable and completely biodegradable.1,2 The
degradability of starch is one of its most relevant advan-
tages as a material for biomedical and disposal purposes.3
In mechanical applications, starch is a stiff polymer that has
a high Young’s modulus and low elongation at break.
Starch-based materials are used in very different applica-
tions in daily life. Bags, mulch films, wrapping films, paper
laminations, nets, cutlery, flower pots, boxes, and trays for
both food and nonfood articles are some examples of
starch-based materials used every day.4 In biomedical appli-
cations, starch is a noncytotoxic and biocompatible polymer
that can induce attachment and proliferation of osteoblast-
like cells.5–7 Starch-based materials have been widely used
as biomaterials such as in bone replacement/fixation and/
or tissue engineering scaffolds.8–16 Also, some research has
applications.17–20
Starch consists of two main polysaccharides: amylose
and amylopectin. As demonstrated in Figure 1, amylose is
essentially linear while amylopectin is highly
branched.22–24 Starch cannot be processed through conven-
tional plastic technology without further modification
because its degradation begins at a temperature lower
than its melting point.25 Addition of water or other plasti-
cizers, such as glycerol, to starch could decrease the glass
transition temperature of the latter.26 In general, when
starch is heated with water, its native crystalline structure
is disrupted and the compound irreversibly swells to a size
much bigger than its original. This phenomenon is known
as gelatinization (Fig. 2).21 Gelatinization transforms a
granular starch into a thermoplastic-like material.27 Thus,
modulating the properties of thermoplastic starch (TPS)
from a soft material (high plasticizer level) to a brittle
material (low plasticizer level) is possible by varying its
moisture and glycerol content.28

Correspondence to: S. A. A. Ghavimi; e-mail: ghavimi@aut.ac.ir

Contract grant sponsor: High Impact Research Grant from the University of Malaya; contract grant number: UM.C/HIR/MOHE/ENG/10 D000010-
16001

C 2014 WILEY PERIODICALS, INC.

V 1

FIGURE 1. Chemical and physical structure schematic of amylose (a)
and amylopectin (b).21
TPS, unfortunately, is a very hydrophilic material; thus,
its performance in highly humid environments is limited
because of increases in its gas permeability and decreases
in mechanical properties and dimensional stability.27,29
Moisture sensitivity and fast hydrolysis can limit starch
applications as a biomaterial.30–32 Thus, various physical
and chemical modifications of starch granules have been
conducted to address its defects; these modifications include
blending33,34 and grafting.35,36 Some researchers have tried
to modify the structure of starch through acetylation to
reduce the hydrophilic character of the chains. However,
this chemical process results in inferior mechanical proper-
ties and greater product cost.28,37 Thus, blending starch
with other biodegradable and biocompatible polymers is
considered the most effective strategy to overcome these
defects.38–43
Polycaprolactone (PCL) is one of the earliest polymers
synthesized by the Carothers group in the early 1930s.44
PCL can be prepared through ring opening polymerization
FIGURE 2. The schematic of gelatinization process.21
2 POLYCAPROLACTONE/STARCH COMPOSITE
of E-caprolactone.45 PCL is a hydrophobic, semicrystalline,
biocompatible46,47 polymer. It has good solubility, a low
melting point, and exceptional blend-compatibility.48,49 PCL
can easily be processed at relatively low temperatures and
presents a total degradation of 2 to 4 years, depending on
its molecular weight.50,51 The mechanism of PCL degrada-
tion can be attributed to random hydrolytic chain scission
of the ester linkages, which causes a decrease in its molecu-
lar weight.52–54 Many researchers agreed that, low degrada-
tion rate can affect PCL applications as degradable
biomaterials.55,56
PCL is widely used in different biomedical applications,
such as tissue engineering, drug delivery, and medical devi-
ces. It appears to be a suitable polymer for different tis-
sues,57–60 including bone,61–64 cartilage,65,66 tendon,67
cardiovascular tissue,68 blood vessel,69,70 skin,71,72 and
nerve.73 PCL is suitable for controlled drug delivery because
of its high permeability to many drugs, excellent biocompat-
ibility, and complete excretion from the body once biore-
sorbed. Several attempts have been exerted to use PCL in
preparing a number of micro-74–76 and nanospheres77–79 for
controlled drug delivery. A number of drug delivery devices
fabricated with PCL have already been patented in the
United States of America.80–82 PCL has also been widely
applied in medical devices, such as sutures,83 wound dress-
ings,84 contraceptive devices,85 fixation devices,86 and den-
tistry.87,88 However, its low melting point makes it difficult
to process using conventional techniques, bringing about
high production costs and limitations in its commercial
use.22 For instance, films produced through film blowing are
especially sticky at extrusion and characterized by low melt
strength at temperatures higher than 130 C.4 The low deg-
radation rate of PCL also limits its use in some applications,
such as tissue engineering. To overcome these problems,
blends of PCL with other polymers, especially biopolymers,
have been studied to obtain a less-expensive degradable
polymer.89,90
Recently, many research groups tend to utilize PCL and
starch (SPCL) composites in several biomedical and indus-
trial applications.91–100 The composite of a stiff natural poly-
mer (starch) and a thermoplastic flexible synthetic polymer
(PCL) offered many advantages. PCL can overcome high
moisture sensitivity of starch which is the most important
weakness of starch as biomaterials.28 Also, PCL can improve

FIGURE 3. (a) The rapid prototyped (three-dimensional blotting) SPCl patterns with 1 to 2 mm width in glass cover slip.111 (b) the co-extrude
device used for creating three layered film of starch/PCL/chitosan.109 (c) Tubular scaffolds produced through three-dimensional plotting rolled
up around a cylinder.110. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
the processability of starch and reduce its high stiff-
ness.101,102 On the other hand, starch can promote PCL bio-
degradability for many bio-performance and reduce the high
cost of the final products.4 As a result, blends of PCL and
starch have controllable degradation and mechanical prop-
erties that are adjustable by changing their component
ratio.90
Because of the high demand for low-cost degradable
polymers and the increasing interest in applications of bio-
compatible and biodegradable polymers as biomaterials,103
we reviewed the available literature on the SPCL composite,
its fabrication methods, structures, properties and its appli-
cation as biomaterial.
FABRICATION OF SPCL COMPOSITES
Several studies have focused on the fabrication of SPCL
composites. Earlier works involved obtaining a simple blend
of starch and PCL. Then, a number of studies have concen-
trated on increasing the efficiency of blending of the two
polymers because poor compatibility between the two
phases can have a negative effect on the physical properties
of PCL when blended with starch.90,101,104,105
Simple methodologies were used by some research
groups to fabricate SPCL constructs. Santos et al.106 fabri-
cated scaffolds through fiber-bonding using fibers obtained
by melt spinning. The fibers were then placed in a glass
mold, heated in an oven, compressed using a Teflon cylin-
der, and then cooled. Gomes et al.107 produced SPCL-based
scaffolds through melt spinning followed by fiber-bonding.
Vertuccio et al.108 produced SPCL scaffolds through ball
milling; here, the milling jars were loaded with different
ratios of PCL, starch, and steel balls. The samples were then
molded and air cooled.
Efforts to obtain more complicated SPCL structures have
also been made. Alix et al.109 fabricated multilayered films
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH A | MONTH 2014 VOL 00A, ISSUE 00
REVIEW ARTICLE
using co-extrusion. PCL/chitosan granulates corresponding
to the external layers of the film were applied to an
extruder, while TPS/PCL blends corresponding to the inter-
nal layer of the film were applied to another extruder. Silva
et al.110 also obtained tubular scaffolds by rolling up porous
sheets produced through three-dimensional plotting around
a cylinder and subsequent heat treatment for adhesion
between filaments. At the same time, Salgado et al.111 pro-
duced parallel SPCL filaments patterns on the surface of
poly(D-lysine)-coated polystyrene coverslips using rapid pro-
totyping, three-dimensional bioplotting. Martins et al.112
produced hierarchical fibrous scaffolds using commercial
SPCL powders. The nanofiber meshes were previously pro-
duced through electrospinning. Then, three-dimensional
rapid prototyping scaffolds were fabricated through a three-
dimensional plotting technique. Production of hierarchical
fibrous scaffolds was achieved through integrating nanofiber
meshes in every two consecutive layers of plotted microfib-
ers. Duarte et al.113 fabricated SPCL scaffolds using super-
critical fluid technology. SPCL solution in chloroform was
loaded in a stainless steel cap that was placed inside a high-
pressure vessel. High-pressure carbon dioxide was pumped
inside the vessel, and the system was closed for 45 min to
allow phase separation. Figures 3 and 4 demonstrate the
methods and morphology of the scaffolds produced by sev-
eral research groups.
To obtain more compatible polymeric systems, several
researchers attempted to plasticize starch to enhance its
processability and prepare SPCL blends. Matzinos et al.4
prepared TPS using glycerol; the PCL/TPS composite was
produced through extrusion, injection molding, and film
blowing. Averous et al.28 obtained TPS by high-speed dis-
persion of glycerol and native potato starch in distilled
water. TPS and PCL were then extruded through a single
screw extruder and injected into molds. Vikman et al.115
added native potato starch, water, and glycerol to a mixer.
3
FIGURE 4. Morphology of SPCL scaffolds which were fabricated with different methods: (a) the side view m-ct (1), the side view SEM (2), top view
m-ct (3) micrographs of tubular SPCL scaffolds made by rapid prototyping (three-dimensional blotting).110 (b) m-ct and SEM micrographs of SPCL
fiber bonded scaffolds.114 (c) The rapid prototyped (three-dimensional blotting) (1 and 2) and hierarchical structure (3 and 4) SPCL scaffolds.112
After starch gelatinization, PCL was added and the blends
were compression molded. Shin et al.116 plasticized starch
with glycerol using a twin-screw co-rotating extruder. Then,
PCL and TPS were blended using the same extruder; and
then compression molded. Myllymaki et al.117 added PCL,
starch, and glycerol simultaneously in a co-rotating twin-
screw extruder to obtain blends.
To enhance the blending process, some researchers
dried starch prior to blending89,90,101 because moisture in
the starch can be trapped in the SPCL structure. Interfacial
tension increases because of the hydrophobic nature of PCL,
which may cause composite failure.
To improve blending efficiency and achieve more com-
patibility between the immiscible PCL and starch, different
research groups applied several modification methods to
starch, including adding a compatibilizer, physical modifica-
tion of starch by coating the starch granules, crosslinking of
the starch granules, and chemical modification of starch by
grafting reactions. Few studies are devoted to the modifica-
tion of PCL. Table I summarizes some of the methods used
by researchers.
STRUCTURE OF SPCL COMPOSITE
Starch and PCL are completely different in nature. As dis-
cussed earlier, starch is highly hydrophilic whereas PCL is
hydrophobic. This difference can cause phase separation
during blending. However, many studies have proven that
4 POLYCAPROLACTONE/STARCH COMPOSITE
starch and PCL can form compatible blends by hydrogen
bonding interactions between the ester carbonyl of PCL and
the -OH groups of starch. Thus, many researchers have
reported the immiscibility and phase separation of the com-
ponents of SPCL composite. The morphology of SPCL com-
posites indicates that the starch phase size increases with
increasing content, likely because of the poor compatibility
between starch and PCL.104 Matzions et al.4 studied the pre-
cise morphology of SPCL (Fig. 5), and scanning electron
microscopy (SEM) results showed that, at up to 40% starch,
droplet-like particles with homogeneous dispersion through
PCL matrix could be maintained. However, beyond 40%,
starch particles show a great tendency to form clusters.
Rosa et al.132 showed that blending PCL with highly linear
starch would form a well-dispersed two-phase structure.
Differential scanning calorimetry133 revealed that the melt-
ing and glass transition temperatures of PCL are almost
unchanged even after blending with starch. Thus, this blend
is thermodynamically immiscible.28,116,134 Thermal gravi-
metric analysis (TGA) data also show that the maximum
decomposition temperatures of PCL and TPS are about 430
and 320 C, respectively. This fact confirms the thermody-
namic immiscibility between PCL and TPS.116 Moreover, the
small decrease in the temperature of SPCL fusion in com-
parison to that of PCL shows separation of the two poly-
meric systems.22 Although most research groups report that
SPCL melting and glass transition temperatures remain
unchanged, Matzions et al.4 declared that addition of TPS
 REVIEW ARTICLE

TABLE I. Methods of Enhancing Blending Efficiency by Modifying Starch or PCL

Research Group Methods Agents

118
Liao et al. Locating a layer of polyurethane at the interface of PCL-based polyurethane
starch and PCL matrix
Avella et al.119 Adding precompatibilizer Pyromellitic anhydride
DemirgoEz et al.2 Crosslinking SPCL powder NA3P3O9
Kalambur and Rizvi120 Crosslinking of starch with PCL and using it as Fentons (H2O2 and Fe21)
compatibilizer
Yavuz and Babaç121 Modifying starch by reaction of hydroxyl group on Trisodium trimetaphosphate
starch surface
a
S rka et al.122 Modifying starch by producing starch acetate Acetic anhydride
Kweon et al.123,124 Modifying starch by producing chlorinated starch Methanesulfonyl chloride in
dimethylformamide solution
Singh et al.125 Hydrophobic coating of starch particles n-butylisocyanate or
octadecyltricholorosilane
Dubois et al.105 Ring opening polymerization of PCL in starch and cata- Sn(Oct)2
lyst presence
Dubois et al.105 Ring opening polymerization of PCL in starch presence Titanium tetrabutoxide, alumi-
and using initiators num tri-sec-butoxide or alu-
minum isopropoxide
Dubois et al.105 Ring opening polymerization of PCL by reaction of Triethylaluminium
starch hydroxyl functions and initiator
125
Singh et al. Grating starch by in situ ring opening polymerization of
caprolactone
Choi et al.126 Using starch-graft-PCL as a compatibilizer
Chen et al.37 Modifying starch by graft polymerization of CL on to Sn(Oct)2 and toluene
starch
Chang et al.127 Producing starch-graft-PCL in presence of catalyst Sn(Oct)2
Habibi and Dufresne128 Producing starch-graft-PCL in presence of catalyst Diisocyanate-modified starch
Choi et al.129 Modifying starch by graft polymerization of CL on to Sn(Oct)2 and water
starch
Kweon et al.130 Producing starch-graft-PCL Diisocyanate-terminated PCL
Labet et al.1 Preparing starch nanocrystals by acid hydrolysis besides Aqueous H2SO4 besides phe-
modifying PCL nylisocyanate and toluene 2,
4-diisocyanate
Wu et al.104,131 Modifying PCL by producing acrylic acid grafted PCL Acrylic acid, benzoyl peroxide
Singh et al.125 Using PCL-g-dextran as a compatibilizer Dextran

causes a small decrease in PCL melting temperature. The
researchers proved that this slight decrease in melt tempera-
ture is caused by hydrogen bonding between the hydroxyls of
starch and the carbonyl of PCL at the interface region. These
observations could also be attributed to the presence of
starch and its effect on PCL crystallites. Spevaček et al.135
found out that blends of starch/PCL are phase-separated even
at a larger scale of 20 to 110 nm. NMR results show, however,
that blending affects the molecular mobility of starch. This
indicates some miscibility in the amorphous channels of the
starch, which are spacious enough (diameter, 100–300 nm) to
accommodate relatively large domains of PCL.
Interfacial properties of PCL and starch can be improved
by addition of some compatibilizing agent to the composite.
Singh et al.125 reported better interfacial properties by add-
ing poly(ethylene glycol) into PCL. Wu131 also reported bet-
ter dispersion and homogeneity of starch in the polymer
matrix when PCL is replaced by PCL-g-acrylic acid, which
results in lower melt viscosity and better mechanical and
thermal properties. In another study by Wu,104 they
observed improved miscibility of starch in PCL-g-acrylic
acid, decreases in melting temperature, increases in fusion
heat, and reduction of starch phase size. These observations
are attributed to the different crystalline structures of PCL-
g-acrylic acid caused by formation of ester-carbonyl func-
tional groups. According to Kweon et al.,124 the enthalpy
values of chlorinated starch and PCL blends were about 50
J/g, though the corresponding value for pure PCL and SPCL
were 72.39 and 70.51 J/g. The decrease in the enthalpy
value of chlorinated starch and PCL blends was due to
improved miscibility caused by more efficient chemical reac-
tions between the chloride groups of starch and the
hydroxyl groups of PCL.
Evaluations of the crystallinity and crystallization behav-
ior of SPCL blends reveal that starch acts as an effective
nucleation agent for PCL that can speed up crystallization.
This finding indicates that the crystallinity of PCL within
SPCL is larger than that in pure PCL. The concentration of
spherulites is higher in SPCL than in PCL; the size of spher-
ulites, however, is smaller in the former than in the lat-
ter.108,136,137 However, the crystallinity of the SPCL
composite is lower than that of pure PCL. Moreover, the
greater the starch ratio, the greater the decrease in crystal-
linity.22 Wu104 believed that the decrease in crystallinity is
probably due to the starch prohibiting the movement of the
polymer segment, which causes difficulty in rearranging the

JOURNAL OF BIOMEDICAL MATERIALS RESEARCH A | MONTH 2014 VOL 00A, ISSUE 00 5

FIGURE 5. The SEM micrographs of PCL/TPS specimen with (a) 10, (b) 20, (c) 30, (d) 40, and (e) 50 wt % starch content. After 40% starch content,
the dispersed granules showed tendency to form clusters.4
polymer chain. The hydrophilic nature of starch and its
poor adhesion with the hydrophobic PCL can motivate the
decrease in crystallinity of the blend.
PROPERTIES OF SPCL COMPOSITE
Mechanical properties of SPCL
Mechanical properties are of great importance for any appli-
cation because the construct must be able to maintain sta-
ble conditions and withstand all loads from the
environment. The law of mixtures states that when poly-
mers are miscible, the resultant blend properties are close
to the sum of the polymer properties (as a function of their
proportions); however, when polymers are not miscible,
their properties are even lower. Several researchers studied
the mechanical behavior of SPCL composites, including the
parameters that can influence this behavior. Several
researchers also showed that low adhesion between starch
and PCL is due to poor interfacial interactions leading to a
decrease in mechanical properties. However, the SPCL com-
posite obviously behaves as a thermoplastic polymer; thus,
6 POLYCAPROLACTONE/STARCH COMPOSITE
it undergoes elastic deformation followed by plastic
deformation.
An increase in Young’s modulus was observed by
increasing the starch content of the composite; decreases in
tensile strength and elongation at break, however, were also
observed. Researchers agree that this behavior is due to the
effect of rigid particles as fillers of thermoplastic poly-
mers.116,117 As PCL is flexible whereas starch is highly stiff,
starch high Young’s modulus can increase the resultant
Young’s modulus of the composite.101,138,139 Averous
et al.28,140 evaluated the effect of adding PCL to TPS and
observed that when the glycerol content is 10%, increasing
PCL contents decreased the Young’s modulus and tensile
strength of the composite; at higher glycerol contents, how-
ever, the mechanical properties of PCL were enhanced. The
authors also found that when starch has a glassy behavior,
addition of PCL can decrease the Young’s modulus of the
composite; by contrast, adding PCL to starch with a rubbery
behavior can improve the mechanical properties of the
product. The same results were obtained by Lim et al.141

Addition of large amounts of glycerol to highly thermoplas-
tic causes a reduction in the Young’s modulus of the SPCL
compared with that of pure PCL. Reductions in the tensile
strength of SPCL compared with that of PCL are explained
by increases in starch particle size, which causes coales-
cence, as well as the low compatibility and interfacial adhe-
sion between PCL and starch.4,142
As discussed earlier, starch and PCL are immiscible, and
any changes affecting their compatibility will alter their
mechanical properties. Campos et al.143 observed increases
in tensile strength, elongation at break, and elasticity modu-
lus of SPCL composites after UV irradiation. Sarka et al.122
reported an increase in elastic modulus and strength of PCL
composites with acetylated starch in comparison with those
of composites obtained from native starch. According to
Yavuz and Babaç,121 crosslinked starch composited with
PCL shows improved tensile strength and elongation at
break. Wu131 grafted PCL with acrylic acid and then blended
it with starch, thereby yielding greater tensile strength and
elongation at break compared with the ungrafted PCL-starch
composite. Odusanya et al.101 declared that pre-dried starch
mixed with PCL yields better tensile strength because the
moisture of the native starch is trapped in the hydrophobic
PCL construct, which could act as a second filler or void
that cause stress concentration and failure. Avella et al.119
used a precompatibilizer while blending starch and PCL, sig-
nificantly increasing the modulus of the final product. Koe-
nig and Huang144 observed that PCL/HA-corn starch blends
have better mechanical properties than SPCL because of the
small granule size and good dispersion of HA-corn starch
granules in the PCL matrix.
Degradation of SPCL composite
As soon as the SPCL composite is immersed in an aqueous
environment, its interaction with the surrounding fluid
begins and water uptake and degradation process take
place. Higher water uptake enhances the hydrolysis pro-
cess.145 Studying the water uptake of degradable SPCL is
important because the composite consists of both hydro-
philic and hydrophobic components, which can affect the
degradation and susceptibility to hydrolysis of the compos-
ite. Many researchers have studied the biodegradation of
SPCL in aqueous solution. Mano et al.146 described the deg-
radation of SPCL in three phases: mass loss because of addi-
tive leaching, degradation of starch, and degradation of PCL.
The most important factor influencing SPCL composite deg-
radation is the component ratio. According to Shin et al.,116
the biodegradability of SPCL increases with increasing
starch content. Blends containing greater starch contents
underwent more rapid degradation during the first few
days of immersion, which is due to starch degradation,
which creates holes and speeds up blend degradation. Rosa
et al.22 reported that by increasing the starch content of the
blend, the extent of composite degradation can be increased.
Other factors crucial in controlling water uptake and SPCL
degradation include morphology of the component, orienta-
tion of the construct, porosity, additives used, and further
modification. Gomes et al.145 evaluated the water uptake of
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH A | MONTH 2014 VOL 00A, ISSUE 00
REVIEW ARTICLE
SPCL fiber mesh, which significantly increased in compari-
son with compact SPCL prepared under the same condi-
tions. The authors declared that improvements in water
uptake are due to the high surface-to-volume ratio of the
fiber meshes. Vikman et al.115 suggested that ball-milled
SPCL samples show higher degradation rates because of
increases in surface area. Duarte et al.113 investigated the
effect of surface porosity on water uptake and concluded
that macroporosity can have a great influence on water
uptake; in this experiment, the authors found that the scaf-
fold they created through supercritical assisted phase inver-
sion has same water uptake as the fiber bonding scaffolds
synthesized by Gomes et al.,107 likely because of the similar
porosities and pore interconnectivities of the scaffolds.
As described earlier, the orientation of the construct can
change its water uptake capability. A precise study on SPCL
surfaces was conducted by Pashkuleva et al.,147 who
revealed that the surface and bulk compositions of SPCL are
completely different. The dominant presence of PCL may be
observed on the surface of constructs, which is caused by
processing techniques that can reversely affect degradation.
Alix et al.109 produced a three-layer film through extrusion
and found that the external layer is mainly composed of
PCL. Water penetration into this film was limited compared
with that in one-layer films. Myllymaki et al.117 blended
starch and PCL with glycerol and then oriented a film. In
this study, the water permeability decreased likely because
the PCL was oriented in such a way as to prevent water
uptake during processing. According to the literature, the
higher the miscibility of PCL in conventional plastics, the
lower its degradation will be. As such, chemical modifica-
tions and additives that compatibilize the two phases of
SPCL composite can have a great influence on SPCL degra-
dation.115,148 Chemical manipulation of starch through chain
modification can change the kinetics and decrease the rate
of SPCL degradation. DemirgoEz  et al.2 found that cross-
linked starch can inhibit chains with low molecular weight
from diffusion from macromolecular domains to the film
surface. Wu104 grafted PCL using maleic anhydride and
observed more water resistance. Due to poor adhesion of
starch to PCL, water resistance in the SPCL composite is
less than that in PCL-g-maleic anhydride as the latter forms
an ester carbonyl functional group, which causes lower
water absorption. Di Franco et al.149 claimed that low fiber
contents improve water uptake in sisal fiber and SPCL
blends; however, as the fiber content increased, this effect is
reversed. Cellulose fibers first act as channels that acceler-
ate water penetration but then inhibit water penetration
with increasing content because of strong fiber-fiber and
fiber matrix interactions.
Polymer degradation is known to be affected by several
specific enzymes depending on the interactions between the
enzymes and polymeric chains.150 In the case of SPCL, a-
amylase151 and lipase152 are well known to accelerate deg-
radation of the composite by interacting with starch and
PCL, respectively. Duarte et al.113 indicated that the mass
loss of SPCL samples immersed in a solution containing
a-amylase and lipase noticeably increased. However,
7
a-amylase alone does not influence SPCL degradation. Pash-
kuleva et al.147 also observed that lipase induces faster deg-
radation compared with a-amylase. This difference is
probably due to the hydrophobic character of PCL, which
inhibits diffusion of water and a-amylase into the bulk. Aze-
vedo and Reis153 encapsulated a-amylase into the SPCL
structure and observed significant accelerations in degrada-
tion rate. This finding supported the idea that PCL inhibits a-
amylase penetration into the bulk because of the high hydro-
phobicity of the component. Gomes et al.145 claimed that the
co-effect of lipase and a-amylase causes slower degradation
compared with lipase alone. This finding could be attributed
to absorption of a-amylase into the SPCL surface, which
reduces the surface area available for lipase penetration.
Other enzymes accelerating SPCL degradation include
proteinase K,22 amyloglucosidase,154,155 and glucoamy-
lase,150 which have similar functions as a-amylase and
slightly accelerate degradation by affecting starch.
Enhancing SPCL properties by compositing with
other materials
To enhance SPCL composite properties, particularly their
mechanical properties, research devoted to compositing
SPCL with other polymers or ceramics has been undertaken.
Taghizadeh and Favis156 dispersed carbon nanotubes with
PCL and TPS to improve the morphology and mechanical
properties of the SPCL blend. Perez et al.157 enhanced the
fracture behavior and toughness of a commercial SPCL
blend (MaterBi-Z) by reinforcing them with montmorillon-
ites Cloisite 30B and Cloisite 10A, respectively. Vertuccio
et al.108 added sodium montmorillonite to SPCL blends, thus
producing an increase in elastic modulus of the composite.
TPS and PCL biocomposites with sisal bleached fibers have
also investigated by Campos et al.,158 who found an increase
in crystallinity because of the good dispersibility of the
fibers and consequent improvements in mechanical proper-
ties. The same results were obtained by Carmona et al.159
Campos et al.143 reported a decrease in crystallinity by addi-
tion of high contents (10%) of sisal fiber caused by a
decrease in lamellar distance and increase in crystalline dis-
order. Perez et al.160 melt-intercalated organo-modified
nanoclay to commercial SPCL blends and obtained signifi-
cant improvements in creep resistance. Matzinos et al.161
fabricated low-density polyethylene/plasticized SPCL blends
and observed better mechanical properties and increased
biodegradability. According to Fei et al.,162 adding nano-TiO2
to the SPCL composite formed an interpenetrating network
structure that significantly improved the mechanical proper-
ties and water resistance of the composites. However, the
transparency of the product decreased. Jukola et al.163
proved that the initial mechanical properties of SPCL are
enhanced by reinforcement with bioactive glass fibers.
Research to improve the other properties of SPCL has
been conducted. Alix et al.109 added chitosan to SPCL com-
posites to reduce the bacterial adhesion potential of packag-
ing for food applications. Mariani et al.133 added soy protein
isolate and sorbitol to SPCL blends with the aim of balanc-
ing the C/N ratio of the blend and control biodegradation.
8 POLYCAPROLACTONE/STARCH COMPOSITE
However, while the starch and soy protein isolates reduced
the thermal and mechanical properties of the materials
compared with those of PCL, reducing the starch ratio could
recover these properties. Wu et al.90 used clay in SPCL to
develop a “controlled-release” bacterial fertilizer with con-
trolled degradation behavior. Sisal fiber-reinforced SPCL
blend was produced by Di Franco et al.149 to control com-
posite hydrolysis. The fibers favored water uptake, swelling,
and starch hydrolysis. At higher fiber contents, however, the
composites become more hydrolytically stable, probably
because of the presence of a physical fiber-fiber network.
Cyras et al.164 also used sisal fibers to increase the Young’s
modulus of SPCL and found that increases in fiber content
cause a reduction in the creep compliance of the composite.
No improvement in crystallization of SPCL was observed.165
PCL/starch/pine-leaf composites were prepared by Kim
et al.166 to obtain biodegradable food packaging materials
with a natural pine flavor. Adding pine-leaf to the composite
brought about good interfacial adhesion between the PCL
matrix and the starch fillers. Table II summarizes research
focusing on composites of SPCL with other materials.
BIOMATERIAL APPLICATIONS OF SPCL COMPOSITE
To utilize biomaterials as a biodegradable substitute in body
tissues, important features to control are biological and
mechanical properties and biodegradation behaviors. As dis-
cussed earlier SPCL has higher modulus and lower strength
compared with PCL. The dominant agent controlling the final
mechanical properties is composite component ratio, which
make it possible to design a highly stiff (more starch content)
biomaterials or more flexible and thermoplastic (more PCL
content) one. Controllable mechanical behavior which can
adjust different tissues made SPCL appropriate for different
biomedical applications. Besides, SPCL inhibits fast starch
degradation and promotes slow PCL degradation. Obviously,
the controllable degradation can adapt different tissue regen-
eration rate. So, starch compounded with PCL offer the
opportunity of controllable degradation and mechanical prop-
erties as well as combining the processability and better
mechanical withstand of synthetic polymer (PCL) with affin-
ity of natural polymer (starch). These advantageous over
many other existing polymeric composites drew researchers’
attention to applying SPCL as biomaterials.
SPCL biomaterials have proven to be biocompatible, and
they do not promote any inflammatory response. Marques
et al.167 determined that SPCL substrates do not promote
inflammatory responses by evaluating leukocyte activation
and adhesion on SPCL surfaces. They reported the low poten-
tial of SPCL to induce inflammation. They also subcutane-
ously installed starch-based implants in a rat model and
observed no inflammatory response.168 Santos et al.169 eval-
uated the inflammatory response of SPCL composites after
subcutaneous and intramuscular implantations in rats. Nor-
mal progress of inflammation was provoked by implantation
of the SPCL composite. However, no fibrotic capsule was his-
tologically observed surrounding the fibers of the scaffolds.
Scaffolds induced a moderate inflammatory reaction after
 REVIEW ARTICLE

TABLE II. Composite of SPCL with Other Materials and the New Properties

Research Group The Composited Component The Properties Enhancement

149
Taghizadeh et al. Dispersing carbon nanotubes To improve the morphology and mechan-
ical properties
 rez et al.150
Pe Reinforcing with montmorillonites Cloisite To enhance fracture behavior
30B
 rez et al.150
Pe Reinforcing with montmorillonites Cloisite To enhance fracture toughness
10A
Vertuccio et al.106 Adding sodium montmorillonite To increase in the elastic modulus
Campos et al.151 Compositing with sisal bleached fibers To increase in crystallinity and improving
of mechanical properties
Carmona, et al.152 Compositing with sisal bleached fibers To improve mechanical properties
Perez et al.153 Melt-intercalating organo-modified To improve creep resistance
nanoclay
Matzinos et al.154 Adding Low-density polyethylene To improve mechanical properties and
increase biodegradability
Fei et al.155 Adding nano-TiO2 to SPCL To improve mechanical properties and
water resistance
Jukola et al.156 reinforcing with bioactive glass fibers To enhance initial mechanical properties
Alix et al.107 Adding chitosan to SPCL To reduce the bacterial adhesion potential
Mariani et al.157 Adding soy protein isolate and sorbitol to To control the biodegradation
SPCL
Wu et al.89 Using clay in SPCL To control degradation behavior.
Di Franco et al.143 Reinforcing with Sisal fiber To control hydrolysis of the composite.
Cyras et al.158 Adding sisal fiber to increase young modulus
Kim et al.160 Adding pine-leaf To add natural pine flavor to biodegrad-
able food packaging materials

subcutaneous and intramuscular implantation. More interest-
ingly, long-term implantation in subcutaneous tissues showed
good integration of the SPCL scaffolds into the host tissue
and pro-wound healing cytokine profile expression. Silva
et al.110 further evaluated the inflammatory response of SPCL
scaffolds and showed that hybrid three-dimensional tubular
structures do not cause cell death among the L929 cells in
vitro. No formation of fibrotic capsules was observed after
SPCL was subcutaneously implanted in Wistar rats, which
supports the finding of lack of inflammatory response trig-
gered by the implanted scaffolds. After implanting the scaf-
folds on a spinal cord injury (SCI) model, no major
inflammation processes around SPCL structures was
observed. Salgado et al.111 reported that hippocampal neu-
rons and glial cells were viable after primary cultures on
SPCL linear parallel filaments deposited on polystyrene cov-
erslips. The results proved low cytotoxicity of the tested
SPCL based biomaterial on neurons and glial cells.
Composite of starch and PCL was extensively used as
biomaterials in different tissue engineering and several drug
delivery devices.
Tissue engineering
Extensive research has been conducted to evaluate the abil-
ity of SPCL composite to enhance tissue repair. Scaffolds
made from SPCL blends have been used in different tissue
engineering applications.170 Figure 6 shows the morphology
of some of the scaffolds made by SPCL.
Bone tissue engineering. One of the most significant bio-
logical specifications of SPCL composites is their ability to
enhance and stimulate osteoblast cell proliferation. SPCL
scaffolds are highly beneficial in bone engineering, as pro-
ven by several research groups.174–176 Wang et al.177 proved
that SPCL exhibits interesting damping properties at 37 C
that are relevant in orthopedic applications. This blend may
help in the dissipation of mechanical energy generated by
patient movements. Pavlov et al.178 declared that fibers
made from SPCL composites possess appropriate mechani-
cal properties for hard tissue engineering. Using different
method of scaffold fabrication and different cell types, many
researchers examined SPCL scaffolds capability for bone tis-
sue engineering.
Gomes et al.107,145,179 focused on the culturing of
highly porous SPCL fiber mesh scaffolds with stromal cells,
harvested from femoras and tibias of Wistar rats, under
both static and flow perfusion conditions. The results
showed the development of adequate in vitro engineered
substitutes for the repair of bone tissue. These scaffolds
were able to induce cell adhesion and proliferation and
enhance the osteogenic differentiation of marrow stromal
cells. Their results demonstrated the potential of these
scaffolds as materials for regenerating bone tissue defects.
Also, they investigated the in vitro localization of several
bone growth factors that are usually associated with bone
formation in vivo by culturing rat bone marrow stromal
cells seeded onto biodegradable fiber-mesh SPCL scaffolds
in a flow perfusion bioreactor. The growth factors includes
transforming growth factor-1, platelet-derived growth
factor-A, fibroblast growth factor-2, vascular endothelial
growth factor, and bone morphogenetic protein-2. Their
results show the presence of regions positively stained for

JOURNAL OF BIOMEDICAL MATERIALS RESEARCH A | MONTH 2014 VOL 00A, ISSUE 00 9

FIGURE 6. Morphology of different scaffolds made by SPCL composite: (a) microscopic image of micro- and nanofiber combined scaffold.114 (b)
SEM image of nanofiber meshes processes using electrospinning.171 (c) SEM image of fiber mesh scaffolds.172 (d) SEM and microscopic image
of fiber mesh SPCL scaffolds.173
all the growth factors considered, except platelet-derived
growth factor-A. They declared that marrow stromal cells,
combined with the use of appropriate biodegradable fiber
meshes, may constitute a useful model to study bone for-
mation and assess bone tissue engineering strategies in
vitro.180 Also, Mendes et al.181 found that rat bone marrow
cells are able to proliferate, differentiate, and form ECM on
SPCL scaffolds. However, compared with hydroxyapatite,
they declared that SPCL still need to be modulated for
higher osteoconductive capacity.
To mimic the biophysical structure of natural extracellu-
lar matrix (ECM), Tuzlakoglu et al.114 developed a nano-
and microfiber combined scaffolds from starch and PCL
composite. The constructs were capable of supporting
human osteoblast-like cell line and rat bone marrow stro-
mal cells proliferation. They proved that the developed
structures have a great potential on the three-dimensional
organization and guidance of cells that is provided for engi-
neering of three-dimensional bone tissues. Also, SPCL scaf-
folds designed and fabricated using the wet-spinning
technique by Tuzlakoglu et al.182 have been used for bone
tissue engineering applications. They observed that SPCL
surfaces are completely covered by osteoblast cells, which
indicates the ability of SPCL scaffolds to enhance osteoblast
attachment and proliferation. The alkaline phosphatase
(ALP) activity of cells cultured on SPCL fiber meshes also
increased with the culture period and modification with Ar
plasma led to higher cell viability and ALP enzyme activity.
Alves et al.,171 also, evaluated the proliferation of
osteoblast-like osteosarcoma cells on both untreated and
plasma-treated SPCL surfaces. Cell adhesion and prolifera-
tion were promoted in both situations.
10 POLYCAPROLACTONE/STARCH COMPOSITE
Martins et al.112 fabricated SPCL scaffolds by mimicking
the morphology of natural ECM using a combination of
micro and nano motifs for bone tissue engineering. Hier-
archical SPCL scaffold was seeded with human osteoblast-
like cells. A homogeneous distribution of cells throughout
the entire scaffold was observed, and osteoblastic cells pref-
erentially adhered to the nanofibrous meshes. Significant
increments in cell proliferation and maturation, assessed by
DNA and ALP activity quantification, were observed along
the culture time. In another study, same research group
seeded fiber-mesh SPCL scaffolds with rat marrow stromal
cells for further bone tissue engineering applications. The
osteogenic media used in their research supplemented with
a-amylase, or with a-amylase and lipase together. It was
observed that SPCL fiber mesh scaffold/MSC constructs cul-
tured with osteogenic medium supplemented with lipase
under flow perfusion were more mineralized, which indi-
cates late stage osteoblastic differentiation of MSCs.183
Rodrigues et al.172,174 implanted SPCL scaffolds seeded
with goat marrow cells and/or amniotic fluid stem cells into
the femur of goat and/or rat and then observed bone neofor-
mation. They, also, prepared a blend of corn starch with PCL
to produce three-dimensional fiber meshes scaffolds by the
wet-spinning technique. After in situ functionalization with
Si–OH groups, in vitro assessment, using human adipose
stem cells (ASCs), were conducted. The scaffolds proved to
exhibit the capacity to sustain cell proliferation and induce
their differentiation into the osteogenic lineage. The forma-
tion of mineralization nodules was observed in cells cultured
on the SPCL scaffolds. Their results indicate the potential of
the scaffolds for bone tissue engineering applications.184,185
Carvalho et al.186 studied bone regeneration potential of
 REVIEW ARTICLE

FIGURE 7. Different cell attachment and proliferation on SPCL substrate: (a) human osteoblast like cells (SAOS-2) seeded on nano- and micro-
fiber combined scaffolds.178 (b) SEM images of SPCL scaffolds which were seeded with bovine articular chondrocytes and cultured for 28
days.190 (c) SEM of rat bone marrow cells cultured on SPCL scaffolds.177 (d) SEM micrographs of HUVEC cells on SPCL nano/micro-fiber-com-
bined scaffold.194 (e) Confocal laser micrographs of stained neurons (left) and astrocytes (right). As indicated by arrows, neurons and astrocytes
were contacting the surface of SPCL directly.111. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

undifferentiated human ASCs loaded in SPCL scaffolds, in a
critical-sized nude mice calvarial defect. Improved new bone
deposition and osseointegration was observed in SPCL loaded
with human ASC engrafted calvarial defects. They declared
that human ASCs enhance ossification of nonhealing nude
mice calvarial defects, and wet-spun SPCL confirmed its suit-
ability for bone tissue engineering. Link et al.187 examined
same fiber-mesh SPCL scaffolds in the regeneration of a
critical-sized cranial defect in male Fisher rats. They reported
high osteoconductivity of the scaffolds to use for bone regen-
eration purposes.
Recently, Requicha et al.188 assessed the behavior of the
double layer scaffold, functionalized with silanol groups or
without in a mandibular rodent model after 8 weeks of
implantation. The analysis revealed that the SPCL scaffolds
induced significantly high new bone formation.
Neural tissue engineering. SPCL composites enhance not
only bone cell proliferation and functionality but also the
viability of other types of cells. Salgado et al.111 evaluated
the effect of SPCL scaffolds on hippocampal neurons and
glial cells for SCI repair. They observed that both neurons
and astrocytes occasionally contacted the surface of SPCL
filaments through their dendrites and cytoplasmatic proc-
esses, respectively, while microglial cells were unable to do
so. Besides hippocampal neurons were observed growing
within the patterned channels. Proliferation of both cell
populations was not negatively affected by the presence of
SPCL filaments which shows SPCL potential ability as a scaf-
fold in SCI regenerative medicine. Silva et al. also, conducted
research on the fabrication of SPCL scaffolds for spinal cord
injuries and found that SPCL scaffolds strongly support the
growth and migration of olfactory ensheathing cells (OECs)
and Schwann cells (SCs). OECs and SCs successfully colon-
ized on SPCL fibers were capable of migrating and growing
on SPCL scaffolds in a three-dimensional manner. These
results indicate that the scaffolds are beneficial for SCI
repair and motor skills improvements.189 In another
research by the same group, three-dimensional tubular
structures of SPCL were developed and a polysaccharide-
based hydrogel of Gellan Gum was injected into the central
area of the structures to encapsulate oligodendrocyte-like
cells. The resultant hybrid structures were very useful in
promoting SCI repair as they integrated within the injured
side of rat hemisection SCI models.110
Cartilage tissue engineering. Research devoted to the
application of SPCL scaffolds in cartilage tissue engineering
has been reported. Oliveira et al.190 observed that SPCL
fiber-based scaffolds may serve as valid alternatives in carti-
lage tissue engineering; these authors proved that SPCL
scaffolds can support bovine articular chondrocyte adhesion,
proliferation, and presented homogeneous cell colonization
throughout the scaffold structure and exhibited acceptable
amounts of glycosaminoglycans. Da Silva et al.191 found that
bovine articular chondrocytes proliferate well in SPCL elec-
trospun nanofiber meshes and are able to produce ECM
under static or dynamic conditions and are therefore appli-
cable for cartilage tissue engineering.
Vascularization in tissue engineering. Synthetic constructs
for biomedical use must favor vascularization because

JOURNAL OF BIOMEDICAL MATERIALS RESEARCH A | MONTH 2014 VOL 00A, ISSUE 00 11

FIGURE 8. SEM micrographs of SPCL microparticles obtained under same experimental condition of 1% PVA as emulsification medium, 600
rpm stirring rate and 4 h experiment time. (a and b) SPCL 5% results in spherical and smooth morphology. (c and d) SPCL 10% results in round
and highly porous morphology.206

ingrowth of tissues can only take place when enough food
and waste transportation in cells are available. Numerous
studies on SPCL scaffolds show that the composite can
enhance vascularization. Ghanaati et al.192 proved that sub-
cutaneously implantation of SPCL can promote formation of
perfused vascular structure within 48 h. According to San-
tos et al.,106 human dermal microvascular endothelial cells
and human osteoblasts seeded in SPCL fiber-mesh scaffolds
recreates a physical and chemical microenvironment favor-
able for the formation of vascular-like structures. They also
examined the co-culture of human umbilical vein endothelial
cell (HUMVEC) together with HPMEC-ST1.6R as a model of
macrovascular and microvascular endothelial cells on fiber
mesh SPCL scaffolds, respectively. The results indicate that
endothelial cells growing on SPCL fiber-mesh scaffolds
maintain a normal expression of EC-specific genes/proteins,
indicating a cell compatibility and potential suitability of
these scaffolds for the vascularization process in bone tissue
engineering in vivo.193 Finally they observed the endothelial
cells growth and proliferation on nano/micro-fiber com-
bined SPCL scaffolds. The architecture of the scaffolds eli-
cited and guided the three-dimensional distribution of ECs
without compromising the structural requirements for bone
regeneration.194 Fuchs et al.195 evaluated the effect of SPCL
scaffolds on vascularization. Human outgrowth endothelial
cells cultured on SPCL fiber meshes supported the vascula-
rization of a complex tissue-engineered construct for bone.
Co-culture of outgrowth endothelial cells with human pri-
mary osteoblasts on SPCL induced angiogenic activation of
OECs toward microvessel-like structures. In Figure 7, the
attachments of some cell strains on SPCL substrates are
shown.
Drug delivery
PCL have been widely used in drug delivery applica-
tions.196–199 Starch and its blend, as well, drew so many
attentions in drug delivery systems.200–205 But SPCL as drug
and biological agent vehicles have only been sporadically
studied. Balmayor et al.206 developed SPCL microparticles
by using an emulsion solvent extraction/evaporation tech-
nique to produce spherical shape particles with size
between 5 and 900 mm with different surface morphologies
(Fig. 8). These microparticular systems appear to be very
promising for controlling the release of dexamethasone. The
drug release was proved to start with diffusion of dexa-
methasone, followed by release to do degradation of SPCL.
Thus, Balmayor et al. proved the functionality of SPCL to
carry differentiation agents in tissue engineering.
CONCLUSION
This article reviews the fabrication methods, structures,
properties, and applications of SPCL composites as biomate-
rials. SPCL composites are fabricated using different simple
methods like mixing and molding or advanced method, such
as rapid prototyping and electrospinning. PCL and starch
are thermodynamically immiscible; however, they can form
compatible blend through hydrogen bonding interactions.
Due to starch hydrophilic nature and weak phase interac-
tion between PCL and starch, the biodegradation rate of

12 POLYCAPROLACTONE/STARCH COMPOSITE

SPCL in aqueous solutions is greater than that of PCL.
Increasing starch contents can increase both water uptake
17.
and hydrolysis and control biodegradation rate of SPCL for
many biomedical applications. Blending starch with PCL
causes a decrease in mechanical strength and an increase in
18.
modulus. Thus, mechanical properties alter with component
ratio. The SPCL composite does not promote any inflamma-
tory response. It mainly enhances osteoblast-like cell differ- 19.
entiation and proliferation. Blend of starch and PCL has
been widely used as biodegradable materials for many tis-
20.
sue engineering applications, such as bone, cartilage and
spinal cord. Also, SPCL proved to be capable of enhancing 21.
further vascularization. However, potential of this composite
22.
in drug delivery applications were not much studied.
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