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Nanofibrous scaffolds electrospun from elastomeric biodegradable poly(L-lactide-co-ε-

caprolactone) copolymer

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2009 Biomed. Mater. 4 015019

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IOP PUBLISHING BIOMEDICAL MATERIALS
Biomed. Mater. 4 (2009) 015019 (9pp) doi:10.1088/1748-6041/4/1/015019

Nanofibrous scaffolds electrospun from

elastomeric biodegradable
poly(L-lactide-co-ε-caprolactone)
copolymer
Sangwon Chung1,2, Ajit K Moghe1,2, Gerardo A Montero1,
Soo Hyun Kim3 and Martin W King1,4,5
1
Fiber and Polymer Science, North Carolina State University, Raleigh, NC 27695-8301, USA
2
Joint Department of Biomedical Engineering, North Carolina State University and University of North
Carolina Chapel Hill, Raleigh, NC 27695-7115, USA
3
Biomaterials Research Center, Korea Institute of Science and Technology, PO Box 131, Cheongryang,
Seoul 130-650, Korea
4
College of Textiles, Donghua University, Songjiang, Shanghai 201620, People’s Republic of China
E-mail: martin king@ncsu.edu

Received 8 August 2008

Accepted for publication 25 November 2008
Published 4 February 2009
Online at stacks.iop.org/BMM/4/015019

Abstract
Electrospinning has recently received much attention in biomedical applications, and has
shown great potential as a novel scaffold fabrication method for tissue engineering. The nano
scale diameter of the fibers produced and the structure of the web resemble certain
supramolecular features of extracellular matrix which is favorable for cell attachment, growth
and proliferation. There are various parameters that can alter the electrospinning process, and
varying one or more of these conditions will result in producing different nanofibrous webs.
So the aim of this study was to investigate the effect of material variables and process variables
on the morphology of electrospun 50:50 poly(L-lactide-co-ε-caprolactone) (PLCL)
nanofibrous structures. The morphology of the nanofibers produced was strongly influenced
by parameters such as the flow rate of the polymer solution, the electrospinning voltage and
the solution concentration. The diameter was found to increase with solution concentration in
a direct linear relationship. Finally, it has been successfully demonstrated that by increasing
the rotation speed of the collector mandrel, the alignment of the fibers can be controlled in a
preferred direction. These findings contribute to determining the functional conditions to
electrospin this biodegradable elastomeric copolymer which has potential as a scaffold
material for vascular tissue engineering.

1. Introduction diameters ranging from several microns down to 100 nm

Electrospinning has recently received much attention in
biomedical applications, especially in tissue engineering
[1–17], providing an alternative approach for the fabrication
of unique porous matrices and scaffolds. Electrospinning
is a spinning method that can produce polymer fibers with
5 Author to whom any correspondence should be addressed.
or less. Instead of using air or mechanical pressure and
applied tensile forces for polymer extrusion and attenuation
as with conventional fiber spinning and drawing processes,
it relies on the application of a high-voltage electrostatic
field between the extrusion capillary and a grounded metallic
collector so as to create and attenuate a continuous stream of
polymer [8, 18–20]. The nano scale diameter of the fibers
produced and the structure of the nonwoven web resemble

1748-6041/09/015019+09$30.00 1 © 2009 IOP Publishing Ltd Printed in the UK

Biomed. Mater. 4 (2009) 015019
certain supramolecular features of extracellular matrix (ECM)
[1, 13, 21]. Since the fibers, pores, ridges and grooves in
the basement membrane of ECM all have dimensions on the
nano scale [15], this characteristic is especially important
for the design of blood vessel tissue engineering scaffolds
because the monolayer of endothelial cells grows directly
on the basement membrane in native blood vessels [13].
The small diameter provides a high surface area to volume
ratio, and a high length to diameter ratio which are favorable
parameters for cell attachment, growth and proliferation. It
is hypothesized that the large surface area of nanofibers with
specific surface chemistry facilitates the attachment of cells
and controls their cellular functions [17]. In electrospinning,
depositing nanofibers on a static collector plate produces a
randomly oriented nonwoven fiber matrix; whereas deposition
on a rotating drum or mandrel can produce aligned nanofiber
matrices [13, 22, 23].
There are various parameters that can alter the
electrospinning process and hence influence the structure
and properties of the resulting nanofiber web [9, 24]. For
example, the properties of the solution such as conductivity,
viscosity, molecular weight and surface tension, can influence
the outcome of the spinning process. Controllable processing
parameters such as the electrical voltage applied on the needle
tip, the flow rate of the solution, and the distance between
the needle tip and the collector can also change the results
of the spinning process. Varying one or more of these
conditions will result in producing nanofibers with different
characteristics, and finding the optimal conditions for a specific
polymer/solvent system is critical to obtain predictable and
functional tissue engineering scaffolds.
Poly(L-lactide-co-ε-caprolactone) (PLCL) is a family of
copolymers of polycaprolactone (PCL) and polylactide (PLA)
where the characteristics differ widely according to the ratio
of PCL and PLA and their molecular weights. Studies
have shown that varying the composition of these monomers
changes the mechanical properties, biodegradability and the
physical state at room temperature, ranging from hard solids
and gummy solids to elastomers [2, 25]. The particular PLCL
random copolymer used in this study had a 50:50 L-lactide:ε-
caprolactone mole ratio with a molecular weight (Mw) of
350 000, exhibiting unique elastomeric properties and a single
glass transition temperature below room temperature.
Successful experiments to produce PLCL nanofibers via
electrospinning have been performed using solvents such as
acetone, methylene chloride (MC), 1,1,1,3,3,3-hexafluoro-2-
propanol (HFIP). Both Mo et al [4] and Xu et al [22] have
reported that PLCL scaffolds composed of nanofibers have
demonstrated favorable growth and proliferation of smooth
muscle cells and endothelial cells. Kwon et al [2, 26]
has successfully produced a compliant mechano-active small-
diameter vascular graft via electrospinning. Although these
studies have demonstrated that PLCL copolymers can be
successfully electrospun into nanofibers, they used different
molecular weights and monomer ratios which significantly
altered the processing conditions and structural performances.
Therefore, this study reports for the first time a systematic
investigation of the material characteristics and processing
2
S Chung et al
parameters for electrospinning this particular elastomeric
50:50 PLCL copolymer.
In this study, a number of variables have been
investigated using this specific PLCL copolymer to determine
the operational conditions for electrospinning nanofibrous
scaffolds. Rather than using a statistical experimental design
to determine the effects of both material characteristics and
process variables, the experimental approach relied on the use
of single parameter optimization.
2. Materials and methods
2.1. Materials
A sample of random poly(L-lactide-co-ε-caprolactone)
(PLCL) copolymer was received as a solid bulk polymer from
the Biomaterials Research Center, Korea Institute of Science
and Technology (KIST), Seoul, Korea. The mole ratio of the
two monomers (PLA and PCL) in the PLCL copolymers was
50:50. The average molecular weight of the copolymer was
Mw = 350 000. The samples were shipped and stored in sealed
plastic bags in a vacuumed desiccator.
2.2. Electrospinning
The custom designed electrospinning apparatus (figure 1)
consisted of a high-voltage power supply (Gamma High
Voltage Research, Inc.), an infusion pump (New Era Pump
Systems, Inc.), a plastic syringe, a stainless-steel straight-end
needle (20 gauge), two kinds of collectors and a grounded cage.
For collecting flat samples, a stainless-steel disc collector
plate (15 cm in diameter) was used, and for investigating the
effect of the mandrel rotation speed, rotating stainless-steel
mandrel (3/16 inch in diameter) was inserted instead of the
flat collector. The syringe was mounted horizontally against
the infusion pump and the sample solution was fed at a constant
rate through the syringe to the needle tip. The distance between
the needle tip and the collector was maintained at 15 cm. The
voltage applied to the needle tip was varied in the range of 12–
20 kV. The voltage that was applied to the cage was exactly
half of that applied to the needle tip. The flow rate of the
solution was controlled between 0.5 ml h−1 and 1.0 ml h−1.
To obtain structures with different degrees of fiber alignment,
samples were collected either on a static disc collector plate
or on a rotating mandrel with the rotation speeds of 20, 100 or
200 rpm.
2.3. Solution preparation
Acetone (Fisher Scientific) was selected as the solvent for
electrospinning PLCL copolymer based on the literature
review [2, 4, 12]. Acetone was selected over methylene
chloride (MC) and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP)
due to its ease of use and low toxicity. Solutions with
polymer concentrations varying from 4%, 12%, 15% and
20% (w/v) were prepared. Homogeneous solutions were
Biomed. Mater. 4 (2009) 015019 S Chung et al

Syringe Polymer Solution Rotating Mandrel

Maintained Flow Rate Needle MOTOR
(D=4.5mm)

Collector
Whipping jet
Cage

X kV
1/2 X kV
HIGH VOLTAGE
SUPPLY

Figure 1. Custom designed electrospinning apparatus.

(A) (B)

(C) (D)

Figure 2. SEM micrographs of electrospun fibers spun from PLCL at different polymer concentrations in acetone ((A): 4%, (B): 12%,
(C): 15% and (D): 20% (w/v)).

obtained by slow agitation at room temperature. This was concentrations and the solutions remained clear and stable
done by using a magnetic stirrer at 300 rpm for 3 h. The during storage at room temperature for up to 7 days prior to
polymer was readily dissolved at room temperature for all electrospinning.

3
Biomed. Mater. 4 (2009) 015019
900
800
700
Mean fiber diameter (nm)
600
500
400
300
200
100
0 2
Figure 3. Linear regression of the concentration of PLCL in acetone versus mean fiber diameter (error bars correspond to ±1 standard error).
2.4. Conductivity measurement
The conductivity of the prepared solutions was measured
using an Orion Model 162 conductivity meter (Orion, MA,
USA). Standard 1413 μS cm−1 (Cat. No. 011007) was used
for a routine calibration of the instrument. The conductivity
probe was cleaned with distilled water before and after use.
The conductivity of pure acetone and acetone with sodium
bromide added was compared and reported in μS cm−1. Other
salts, such as ammonium acetate have been investigated in
addition to sodium bromide. However, the rate of dissolution
of ammonium acetate in acetone was too slow for inclusion in
this study.
2.5. Scanning electron microscope (SEM)
In order to determine the morphology and the diameter of
the nanofibers, electrospun samples were viewed under a
scanning electron microscope (SEM). Images were acquired
from a JEOL JSM 5900-LV scanning electron microscope
using an accelerating voltage of 15 kV and spot size 20. Prior
to viewing, the specimens were coated with gold/palladium
using a HummerTM 6.2 Sputter Coating System (Anatech,
CA, USA) to obtain an average uniform coating of 100
Å thicknesses. The specimens were coated five times,
each time depositing a thickness of about 20 Å at different
angles.
2.6. Pore size and fiber diameter measurement by image
analysis
The captured images of electrospun webs were analyzed by
measuring the mean fiber diameters and mean pore areas. The
measurements were performed using Image J software (Java
version), which is commercially available from NIH. Fiber
diameters were measured on 100 randomly selected fibers from
each individual SEM image using the magnification recorded
during SEM viewing. The measurements were performed by
moving the cursor from one side to the other side of each
S Chung et al
y = 38.065x - 9.776
R2 = 0.9821
4 6 8 10 12 14 16 18 20 22
Concentration (w/v,%)
fiber along the transverse direction perpendicular to the fiber
axis. To obtain the pore size distribution, measurements were
also performed manually by first adjusting the contrast and
threshold of each image so as to clearly focus on the pores
of the top layer and then by moving the cursor to the various
edges of the pores so as to identify their relative positions in
the scaffold. The means and standard deviations of the pore
areas were then calculated in μm2.
To determine the fiber orientation, a fast Fourier transform
(FFT) method was used, utilizing Image J software (Java
version). The intensity spectra of the pixels in the image
were decomposed into a frequency domain with appropriate
magnitude and phase values, giving the rate at which intensity
transition occurs in a given direction in the image.
3. Results and discussion
3.1. Morphology
3.1.1. Effect of solution concentration. The effect of the
polymer solution concentration on nanofiber morphology was
evaluated by measuring the mean fiber diameters. The flow
rate for all concentrations was held constant at 0.5 ml h−1,
except for the 20% (w/v) polymer solution, which was fed at
1 ml h−1. This is because the 20% (w/v) polymer solution was
too viscous, so the flow rate was increased from 0.5 ml h−1
to 1 ml h−1 to prevent the clogging of the needle. As the
concentration of the polymer increased, more uniform fibers
were produced. At 4% (w/v) polymer solution, fibers were
produced but still the beads were dominant in the collected
sample (figure 2(A)). At 12% (w/v) polymer solution, although
there was some evidence of fusing fibers, there was a
significant decrease in bead formation and the beads were more
integrated into the fibers (figure 2(B)). It has been reported by
Zong et al [24] that at lower concentrations, not only are
beads formed, but they are slower to dry before reaching the
collector plate. Because of low surface tension, the jet breaks
up into droplets in the case of low viscosity liquids, whereas
4
Biomed. Mater. 4 (2009) 015019
Without sodium bromide
(A)
(C)
Figure 4. SEM micrographs of electrospun fibers showing the effect of conductivity at different polymer concentrations ((A) and (B): 12%,
(C) and (D): 15% (w/v)).
for high viscosity liquids, the jet does not break up and travels
as a continuous jet to the grounded target [9]. It has also
been observed that the shape of the beads changed from being
spherical to spindle like with increased polymer concentration
[27]. In this study, as the polymer concentration increased
up to 15% (w/v), we observed the most uniform fibers
(figure 2(C)). However, when the concentration reached 20%
(w/v), thicker fibers with irregular diameters were deposited
(figure 2(D)). Also since the solution had a high viscosity, it
was hard to maintain the processing conditions and the needle
became clogged.
Mean fiber diameters were compared between the samples
produced from 4%, 12%, 15% and 20% (w/v) polymer
concentrations. The results presented in figure 3 show the
mean fiber diameter in a linear relationship from 160 ± 60 nm
at 4% (w/v) concentration to 760 ± 390 nm for the 20% (w/v)
concentration. This confirms the results of the previous studies
[9, 10, 28], and leads us to recommend the use of a 15% (w/v)
polymer concentration and an applied voltage of 14 kV when
electrospinning this PLCL polymer from acetone.
5
S Chung et al
With sodium bromide
(B)
(D)
It has been reported that using different solvents other
than acetone can affect the diameter of the fibers produced by
electrospinning. Kwon et al [2] have produced thicker fibers,
with a mean diameter of 7 μm, by electrospinning PLCL
copolymer from methylene chloride (MC) solutions. On the
other hand, by using 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP)
as the solvent, they produced electrospun fibers with similar
dimensions to those reported here, i.e. with a diameter range
from 0.3–1.2 μm.
3.1.2. Effect of conductivity. Small amounts of electrically
conductive salt, such as NaCl, R4NCl or LiCl, are known
to increase the conductivity of the electrospinning solution,
stabilize the jet, and decrease the formation of beads [27, 29].
In this study, the conductivity of pure acetone was measured
and found to be 1.3 μS cm−1. By adding 1% (vol/vol)
sodium bromide conductivity increased to 165 μS cm−1.
The morphology of fibers electrospun from 12% and 15%
(w/v) polymer concentrations were evaluated with and without
the sodium bromide. By adding the salt at 12% (w/v)
Biomed. Mater. 4 (2009) 015019 S Chung et al

35

Mean 542 ± 189nm

30

Mean 453 ± 163nm

25

20
Frequency

15
15% PLCL
15% PLCL + Sodium Bromide
10

0
200 300 400 500 600 700 800 900 1000
Fiber diameter (nm)

Figure 5. Fiber diameter distribution with and without sodium bromide.

40

35

30

25
Frequency

20

15
15% PLCL
15% PLCL + Sodium Bromide
10

0
1 2 3 4 5 6 7 8
Pore size (μm 2 )

Figure 6. Pore size distribution with and without sodium bromide.

concentration, there was no improvement in fiber formation,
but increased fusing. However at 15% (w/v) polymer
concentration, the addition of salt reduced the diameter of
the electrospun fibers as shown in figure 4.
The fiber diameter distribution as well as pore size
distribution of the electrospun webs spun with and without
sodium bromide were compared. The diameter distribution of
nanofibers produced from 15% (w/v) polymer concentration
is presented in figure 5. It can be seen that the average diameter
of the fibers without salt was 540 ± 190 nm, which fell
significantly (p < 0.01) to 450 ± 160 nm by the addition
of sodium bromide. Figure 5 also shows the shift of the fiber
diameter distribution.
It has been reported that the addition of salt results in
a higher charge density on the surface of the jet during
electrospinning [24]. As the charge carried by the jet increases,
higher attenuating forces are imposed on the jet by the
electrical field, and the diameter of the final fibers becomes
significantly smaller. However, there was no equivalent shift
in the pore size distribution of the nanofibrous webs when
salt was added. Figure 6 presents the exponential pore area
distributions with and without salt for the 15% (w/v) polymer

6
Biomed. Mater. 4 (2009) 015019
12kv
Figure 7. SEM micrographs of electrospun fibers showing the effect of different applied voltages (electrospinning conditions: 12% (w/v),
1 ml h−1)).
0.5ml/h
Figure 8. SEM micrographs of electrospun fibers showing the effect of different flow rates (electrospinning conditions: 15% (w/v), 14 kV).
concentration. These two distributions overlap each other
and are not significantly different (p = 0.01) when analyzed
statistically.
3.1.3. Effect of applied voltage. To assess the effect
of different applied voltages, polymer solutions with
concentrations of 12% and 15% (w/v) were electrospun using
applied voltages between 12 and 20 kV. It was observed that on
increasing the kV, bead formation was reduced and the nano
fibers increased in diameter. The mean fiber diameter at 12 kV
was only 400 ± 150 nm, whereas at 20 kV, it was 620 ± 240 nm
(figure 7). And when the polymer solution concentration was
increased to 15%, the diameter of the electrospun fibers also
increased.
When the applied voltage is increased, the jet velocity
also increases and the solution is removed more quickly from
the tip of the capillary. The only mechanism for transporting
charge during electrospinning is the flow of polymer from the
7
S Chung et al
20kv
1ml/h
capillary tip to the target since the electric current due to ionic
conduction in the polymer solution is assumed small enough
to be negligible [9]. Thus, an increase in the electrospinning
voltage generally reflects an increase in the mass flow rate
from the capillary tip to the grounded target when all other
variables such as conductivity and solution flow rate are held
constant.
3.1.4. Effect of flow rate. The effect of polymer flow rate on
the resulting nanofibers morphology was studied by increasing
the flow rate from 0.5 ml h−1 to 1.0 ml h−1. It was found
that with a 12% (w/v) solution concentration, fibers with
spindle-like beads were formed at lower feeding rates. At
higher flow rates, the fibers showed more irregularity and non-
uniformity. This trend was consistent with an increase in
polymer concentration as seen in figure 8.
As the solution flow rate increased, the spun nanofibers
became thicker and more irregular. This is because at higher
Biomed. Mater. 4 (2009) 015019
0 rpm
Random
Figure 9. SEM micrographs and fast Fourier transform (FFT) of electrospun fibers showing the effect of rotation speed on diagonal
alignment (electrospinning conditions: 15% (w/v), 14 kV).
flow rates, the droplet suspended at the end of the needle
becomes larger, and the solution jet can carry the fluid away
with a faster velocity [24].
3.2. Effect of rotation speed
To investigate the alignment of the nano fibers at different
take-up speeds, the mandrel rotation speed was increased from
20 rpm (29.9 cm min−1) to 100 rpm (149.5 cm min−1), and
then to 200 rpm (298.9 cm min−1) while collecting the fibers.
A 15% (w/v) solution concentration was used to electrospin
fibers at 0.5 ml h−1 flow rate and at an applied voltage of 14 kV.
Up to 100 rpm, the nano fibers appeared to be collected at
random without showing any directional alignment. However,
at 200 rpm, it was possible to observe some preferred diagonal
alignment. The results are presented in figure 9.
Previously, it has been reported that mandrel rotation
speeds should exceed 1000 rpm before observing any change in
fiber alignment [30]. So contrary to this previous observation,
we were surprised to find that even at 200 rpm our nanofibrous
webs contained oriented fibers that were aligned in a diagonal
direction (figure 9). This alignment was confirmed by
converting the image by a fast Fourier transform (FFT) so
as to observe the relative spatial dimensions between fibers
in the form of brightness transitions. The relevance of
aligned nanofibers for tissue engineering applications is so
as to control cell orientation. It has been observed that cells
8
S Chung et al
200 rpm
Aligned
cultured on electrospun nanofiber scaffolds tend to proliferate
in the direction of the fiber alignment [22]. For example,
in native blood vessels the shear stress caused by blood flow
orientates the endothelial cells in the direction of blood flow,
whereas within the walls of blood vessels, smooth muscle
cells are concentrically aligned around the tubular structure
[13]. Therefore, tubular webs that show fiber alignment in
particular directions are considered preferred candidates as
scaffolds for tissue engineering blood vessels.
4. Conclusions
This work has explored the effects of material variables
and processing parameters on the morphology of electrospun
PLCL nanofibers. We have found that the morphology of the
nanofibers produced is strongly influenced by electrospinning
parameters particularly the polymer solution concentration,
the flow rate of the polymer solution, the applied voltage,
the addition of salt to increase conductivity, and the mandrel
take-up speed. Higher polymer solution concentrations were
found to avoid bead formation and to significantly increase
the diameter of the electrospun PLCL nanofibers. At the
same time finer nanofibers were electrospun by using a lower
applied voltage, a slower flow rate in the capillary and by
adding sodium bromide salt to increase the conductivity of
the polymer solution. In addition, it has been successfully
Biomed. Mater. 4 (2009) 015019
demonstrated that by increasing the rotation speed of the
collector mandrel, the alignment of the fibers can be controlled
in a preferred direction.
Although PLCL copolymers have been reported to
be fairly biocompatible, any residual solvent left from
electrospinning raises the question of cell viability. To answer
this question, a preliminary assay with fibroblasts has shown
that the initial cell viability of the electrospun structure is
low, but after 7 days in culture, it increases to an acceptable
level. This reminds us of the importance of including effective
cleaning and sterilization processes after electrospinning so as
to ensure complete removal of any solvent residue. Based
on these findings, further studies are being conducted to
design a functional tubular scaffold with adequate mechanical
properties and architecture to promote cell growth.
Acknowledgments
The authors acknowledge financial support from Boston
Scientific Corporation and the College of Textiles at North
Carolina State University. We wish to thank Dr. Bhupender
Gupta for his helpful advice and insights and Valerie Knowlton
for her technical assistance with the SEM analysis.
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