Journal of Membrane Science 355 (2010) 5359

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Journal of Membrane Science

journal homepage: www.elsevier.com/locate/memsci

Electrospun PLGA/collagen nanobrous membrane as early-stage wound

dressing
Shih-Jung Liu a, , Yi-Chuan Kau a,b , Chi-Yin Chou a , Jan-Kan Chen c , Ren-Chin Wu d , Wen-Ling Yeh e
a

Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan

Department of Anesthesiology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan
Department of Physiology and Pharmacology, Chang Gung University, Tao-Yuan, Taiwan
d
Department of Pathology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan
e
Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan
b
c

a r t i c l e

i n f o

Article history:
Received 2 February 2010
Received in revised form 3 March 2010
Accepted 5 March 2010
Available online 15 March 2010
Keywords:
Electrospinning
Nanobrous membranes
Polylactidepolyglycolide (PLGA)
Collagen
Cell behavior

a b s t r a c t
Electrospinning of polylactidepolyglycolide (PLGA)/collagen in 1,1,1,3,3,3-hexauoro-2-propanol
(HFIP) to fabricate a biomimetic nanobrous extracellular membranes for wound dressing and tissue
engineering was investigated. The morphology of as-spun PLGA/collagen nanobers was examined by
scanning electron microscopy. The average diameter of electrospun nanobers was 250 nm (range of
150650 nm). Degradation rate of PLGA/collagen nanobrous membranes, cytocompatibility and cellular responses to membranes, cell and nanobers interactions, and open wound healing in rats were
studied. It was found that nanobrous membranes made of PLGA/collagen were functionally active in
responses in human broblasts, and were very effective as wound-healing accelerators in early-stage
wound healing. The empirical results in this study indicate that electrospun PLGA/collagen nanobers
may be a good candidate as a wound dressing for skin regeneration.
2010 Elsevier B.V. All rights reserved.

1. Introduction
The prompt closure of full-thickness wounds is critical for survival for severely burned patients. Split thickness skin grafts are
commonly grafted to the wound to promote recovery [1]. However,
the limited donor sites and the potential advantages of reduced
numbers of surgical procedures and donor site surface areas are the
major impetus for development of bioengineered skin. Considerable effort has been directed towards developing matrices for tissue
engineering using biodegradable and biocompatible synthetic or
natural polymers [29]. An ideal wound dressing candidate should
mimic the structure and biological function of native extracellular
matrix (ECM) proteins, which provide support and regulate cellular activities. In addition, the dressing should also maintain the
normal state of differentiation within the cellular compartment. To
achieve this objective, an engineered matrix must be biocompatible and/or biodegradable, and should not induce adverse effects in
the surrounding tissue.
Wound dressing from electrospun nanobrous matrix (NFM)
potentially offers several advantages over conventional processes
[25]. With its huge surface area and microporous structure, the

Corresponding author. Tel.: +886 3 2118166; fax: +886 3 2118558.

E-mail address: shihjung@mail.cgu.edu.tw (S.-J. Liu).
0376-7388/$ see front matter 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.memsci.2010.03.012

NFM could quickly start signaling pathway and attract broblasts to

the dermis layer, which can excrete important extracellular matrix
components such as collagen and growth factors to repair damaged
tissue. The electrospun membrane is also important for cell attachment and proliferation in wound healing. In the electrospinning
process, a polymeric solution placed inside a syringe is driven out
from a metal capillary that is connected to high voltage power supply. Nanobers are collected in the form of a nonwoven matrix on
a grounded collector after solvent evaporation. By adopting appropriate process parameters such as solvent, polymer concentration,
and ow rate, electrospun nanobers with various diameters can
be obtained [10]. Previous studies have shown collagen and electrospun collagen nanobrous matrices were able to promote wound
healing [69].
Collagen is a natural ECM component of many tissues, such as
skin, bone, tendon, ligament, and other connective tissues. Among
the isotypes of collagen, type I is the principal structural and functional protein and is composed of two 1 chains and one 2 chain.
The underlying chains that form these natural polymers are
arranged into a repeating motif that forms a coiled structure. The
specic complement of subunits present within the bril denes
the material properties of the natural polymer [7]. In native tissues,
type I collagen brils range from 50 to 500 nm in diameter and are
very uniform in size. The brillar structure of type I collagen has
long been known to be important for cell attachment, prolifera-

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tion, and differentiated function in tissue culture [1114]. In native

ECM, collagen exists in a three-dimensional network structure
composed of multi-brils in the nanober scale (50500 nm) [8].
Collagen can be isolated from a variety of sources and is highly conserved and relatively non-immunogenic. A nonwoven-type matrix,
which is composed of nanobers, is easily produced via electrospinning and is architecturally similar to the collagen structure
of ECM. Previous studies of adaptations in electrospinning to produce tissue-engineering scaffolds composed of collagen nanobers
(a matrix composed of 100 nm bers) have found that the structural properties of electrospun collagen vary with the tissue of
origin, the isotope, and the concentration of the collagen solution
[8].
Scaffolds that are intended for cell culture purposes need
to exhibit mechanically supportive properties for cellular morphogenesis. The mechanical strength of electrospun collagen
nanobers can be enhanced with the addition of PLGA materials
[15]. Polylactidepolyglycolide (PLGA) is in the class of synthesized biodegradable and biocompatible copolymers from which
resorbable sutures, resorbable surgical clips, and controlled-release
implants are made. PLGA also falls within the class of copolymers
that have been used for implantable and injectable controlledrelease, drug delivery systems [16,17]. These copolymers have been
approved for, and have a history of safe use in, humans. After being
introduced into the body, PLGA material induces only a minimal
inammatory response and biodegrades through the hydrolysis of
its ester linkages to yield biocompatible lactic and glycolic acids.
Furthermore, the rate at which PLGA biodegrades is a function of
the ratio of lactide to glycolide [18,19].
In the present study, a nanobrous matrix of PLGA/type I
collagen blend was produced via electrospinning to develop
biodegradable and biomimetic scaffolds. To assay the cytocompatibility and cell behavior of electrospun collagen nanobers, cell
attachment and spreading of normal human broblasts seeded on
the PLGA/collagen nanobrous matrix and the interaction between
cells and PLGA/collagen nanobers were studied. Additionally, the
effect of PLGA/collagen nanobers on open wound healing in rats
was examined.

applied to polymer solutions was in the range of 1520 kV. All electrospinning experiments were carried out at room temperature.
2.3. Characterization of nanobers
The morphology of electrospun PLGA/collagen nanobers was
observed on a scanning electron microscope (SEM; Hitachi S-300N,
Japan) after gold coating. The average diameter and diameter distribution were obtained by analyzing SEM images using a commercial
image analysis program (Optimas version 5.22, U.S.A.).
2.4. Water uptake capacity of PLGA/collagen nanobers
The water uptake capacity of PLGA/collagen nanobers was
determined. Electrospun nanobers were rst immersed in distill
water. The sampled were removed from the water at 7, 14, 21 and
28 days and weighed after removing the surface water with a lter
paper. The water content (WC, %) was calculated according to the
follows:
WC (%) =

(W W0 )
100
W0

(1)

where W0 and W are the weight of the samples before and after
immersion in water for different times, respectively.
2.5. Weight variation
Weight variation of PLGA/collagen nanobrous matrix was
monitored by immersing the bers in a phosphate buffer, 0.15 mol/l
(pH 7.4), at 37 C. The sampled were removed from the solutions
and weighed at 7, 14, 21 and 28 days after being dried inside an oven
for 24 h. The weight retention (WR, %) of the nanobrous matrix was
calculated according to the follows:
WR (%) =

W1
100
W0

(2)

where W0 and W1 were the initial weight of the nanobrous matrix

samples and the weight of the samples at different days, respectively.

2. Materials and methods

2.6. pH value measurement

2.1. Materials

The pH values of eluted solution from the NFMs as described in

the above section at 7, 14, 21, and 28 days were monitored by a pH
meter (EuTech Model PH1100, Singapore).

Collagen from bovine achilles tendon, Type I, and 1,1,1,3,3,3hexauoro-2-propanol (HFIP) were purchased from SigmaAldrich
(Saint Louis, MO, U.S.A.). The poly (d,l)-lactide-co-glycolide (PLGA)
used was commercially available materials (Resomer RG 503,
Boehringer, Germany) and had a ratio of 50:50 and an intrinsic
viscosity of 0.4.
2.2. Electrospinning
The electrospinning setup utilized in this study consisted of a
syringe and needle (the internal diameter is 0.42 mm), a ground
electrode, an aluminum sheet, and a high voltage supply. The needle was connected to the high voltage supply, which could generate
positive DC voltages and current up to 35 kV and 4.16 mA/125 W
respectively. For the electrospinning of PLGA/collagen bers, PLGA
and collagen were rst dissolved in HFIP at concentrations of 15%
and 8% (W/V) respectively. A series of PLGA/collagen blend solutions (PLGA solution/collagen solution = 100/0, 80/20, 65/35, 50/50,
0/100, v/v) were prepared by mixing each solution at predetermined ratios and were then delivered by a syringe pump with a
volumetric ow rate of 4 ml/h. The distance between the needle
tip and the ground electrode was 15 cm, and the positive voltage

2.7. Cytotoxicity of electrospun nanobers

Cytotoxicity of the material was examined by MTT assay (Roche,
Germany) of cell viability. Electrospun PLGA/collagen nanobers
were cut out with punch and put onto 24-well culture plates.
Human broblasts obtained from foreskins of patients (13 years
of age) undergoing surgery were seeded (5 103 cells/well) in
Dulbeccos Modied Eagles Medium (DMEM) at 37 C under 5%
CO2 /95% air condition until cell conuence. Cell viability was monitored at 1, 3, 7, and 14 days by MTT assays and quantied using an
ELISA reader.
2.8. Cell cultures
Electrospun PLGA/collagen nanobers were cut out with punch
(14-mm in diameter) and put onto the 24-well culture plates.
Human broblasts were plated at 5 103 cells onto each electrospun PLGA/collagen nanober and cultured for 1 and 2 weeks
at 37 C in 5% CO2 . The culture plates containing PLGA/collagen
nanobers were washed twice with PBS to remove the unattached

S.-J. Liu et al. / Journal of Membrane Science 355 (2010) 5359

55

Fig. 1. SEM images of nanobers with various PLGA/collagen ratios. (A) 100/0, (B) 80/20, (C) 65/35, (D) 50/50, and (E) 0/100.

cells. Attached cells were xed with 99% ethanol solutions for 24 h
and rinsed twice with PBS. After critical point drying (Balzers CPD
030, Liechtenstein, Germany), the samples were sputtered with
gold, using an SEM coating system, and observed by a SEM (Hitachi
S-300N, Japan). In addition, the number of cells was counted under
an optical microscope (Olympus IMT-2, Japan).
2.9. Open wound-healing test
Twelve S.D. rats weighing 375 25 g were used in this study.
After anesthetization, two full-thickness rectangular wounds of
2 cm 2 cm were prepared on each of the rats back, parallel
with the vertebral column. The electrospun PLGA (50:50)/collagen nanobrous matrix were then applied to the wounds of each
rat, while a commercial wound-dressing material (DuoDerm, ConvaTec, U.S.A.) served as a comparison. The same wound was also
treated with gauze sponge as a control. No dressings were replaced
during the whole healing process. On the 7th, 14th and 21st postoperative days, macroscopic photographs of the wounds were taken,
and the wound area was measured using an image analysis program
(Optimas version 5.22, U.S.A.). Additionally, the wound dressing
was removed on the 7th and 21st postoperative days after the rats
are euthanized, for histological examination of epithelialization
and granulation.

in the polymers. The diameters of the spun nanobers ranged

between 170 nm and 650 nm, and the porosity of the nanobrous matrix was high. By adopting different PLGA solution to
collagen solution ratios, nanobers of various diameters could
be successfully fabricated. Fig. 1 shows the SEM micrographs
of the electrospun PLGA/collagen nanobers under magnication
of 3000. Clearly, the diameters of the nanobers varied with
the PLGA to collagen ratios. The image characterization of the
nanobers in Fig. 2 suggests that the ber diameter decreased with
the content of collagen in the blend solutions (ranging from 460 nm
for 100% PLGA to 190 nm for 100% collagen).
3.2. Characterization of the electrospun nanobrous matrix
Variations of water content in PLGA/collagen nanobers were
examined. The results in Fig. 3 shows that water content of the
nanobers increased with time as well as with the collagen. The
presence of collagen in the PLGA/collagen nanobers increases the
wettability of the electrospun matrices, which may promote cell
proliferation in the matrices [16].
The weight variation of the electrospun nanobrous matrix in
aqueous solution was also studied. Fig. 4 shows the weights of the
dried matrix at different days. The pure PLGA matrix showed the

2.10. Statistics and data analysis

Data were collected from quadruplicate samples and were analyzed by one-way analysis of variance (ANOVA). Differences were
considered statistically signicant for p values <0.05.
3. Results and discussion
3.1. Electrospinning of PLGA/collagen nanobers
The fabrication of PLGA/collagen nanobrous matrices via electrospinning is highly desirable because PLGA is non-toxic, elicits
minimal inammatory response and can be eventually absorbed
without any accumulation in the vital organs [18], while collagen
is a principal structural component of the ECM matrix. In this study,
continuous PLGA and collagen nanobers were obtained at a concentration of 15% and 8% respectively by weight, concentrations
that correspond to the onset of signicant chain entanglements

Fig. 2. Variation of ber diameter distribution with the PLGA to collagen ratio.

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S.-J. Liu et al. / Journal of Membrane Science 355 (2010) 5359

Fig. 3. Variation of water content in PLGA/collagen nanobers with time.

Fig. 5. Cytotoxicity tests from MTT assays of cell viability in NFM of various
PLGA/collagen ratios (* p < 0.05).

3.3. Effect of PLGA to collagen ratios on cell adhesion and

spreading of normal human broblasts

Fig. 4. Weight variation of electrospun nanobrous matrices.

greatest decrease in weight, while the pure collagen matrix exhibited the least weight variation. Furthermore, the result in Fig. 4
suggests that while PLGA degraded by 30% in 4 weeks, collagen
only degraded by 10% for the same time. This can be explained
by the fact that while collagen is degraded by mammalian collagenases, naturally occurring enzymes that attack the triple helical
molecules at a specic location, PLGA is a synthetic, biodegradable
material that can be hydrolyzed in aqueous solution. The weight
variations of electrospun PLGA/collagen nanobers in water thus
increased with the content of PLGA.

As a potential wound-dressing material and scaffolding for

tissue engineering, the nanobrous matrix should promote cell
growth and physiological function and should be able to maintain
normal states of cell differentiation. The biological properties of
an electrospun PLGA/collagen matrix in cell culture experiments
and the cytocompatibility of electrospun PLGA/collagen nanobers
were studied. Cytotoxicity tests from MTT assays of cell viability in
nanobrous matrix of various PLGA/collagen ratios were studied
and the result is shown in Fig. 5. All nanobers show no signs of
cytotoxicity. Furthermore, despite PLGA in the nanobrous matrices can be hydrolyzed in aqueous solution and releases lactic acid,
the measured pH values of eluted solution from the NFMs did not
show any signicant variations (7.5 0.13). The possible inuence
of released acid on cell proliferation is negligible. In addition, the
experimental data in Fig. 5 suggested that the 50/50 PLGA/collagen
ratio nanobers exhibited levels of signicance in cell proliferation
during culture. They were thus used for the subsequent woundhealing tests.
The initial cell adhesion and spreading could be important
factors in developing wound dressing and scaffolds for tissue
engineering [2022], the initial cell attachment and spreading of
electrospun PLGA/collagen nanobers were examined. To assess
cell adhesion, PLGA/collagen nanobrous matrices were seeded
with normal human broblasts. The adhesion of cultured broblasts was evaluated using a cell adhesion assay in serum-free
medium. Exponentially proliferating broblasts adherent to the
electrospun PLGA/collagen nanobers were microphotographed in

Fig. 6. SEM images of 50/50 PLGA/collagen nanobrous matrices at (A) 1 week, and (B) 2 weeks.

S.-J. Liu et al. / Journal of Membrane Science 355 (2010) 5359

57

Fig. 7. Appearance of would healings at 1, 2 and 3 weeks after grafting: (A) gauze group, (B) nanobers group, and (C) commercial dressing group (Rectangular wounds of
2 cm 2 cm were prepared on each of the rats back, as shown in A1, B1 and C1.)

the adhesion assay after washing and xing. The SEM microphotos
in Fig. 6 show a high level of cell adhesion of normal human broblasts on the surface of the matrix at 1 week, while in-depth cell
growth was also observed on PLGA/collagen nanobers at 2 weeks.
Kumbar et al. [16] studied the electrospun ber matrices composed
of scaffolds of various ber diameters and reported that human
skin broblasts showed signicantly higher proliferation on electrospun PLGA ber matrices having ber diameter in the range of
3501100 nm. Despite the diameter of the electrospun nanobers
in this study (range of 150650 nm) is less than the reported optimum value, the fabricated nanobrous matrices show good cell
adhesion in normal human broblasts. This might be due to the
fact that the presence of collagen in the matrices promotes cell
proliferation in the electrospun PLGA/collagen nanobers.
On the other hand, while it has been reported that the electrospinning process may denaturalize the biological and structural
properties of a natural protein such as collagen [8], the experimental result in this study suggest that the PLGA/collagen nanobrous
matrix remain intact during the processing procedure and can act
as an excellent scaffold for cell adhesion and growth. Furthermore,
compared to the result of Rho [8], the electrospun PLGA/collagen
nanobers showed good cell adhesion in normal human broblasts, even without being treated with ECM proteins. The results
here suggest that electrospun PLGA/collagen nanobers may be a
good candidate as a wound dressing for skin regeneration.

in the PLGA/collagen nanober group was visibly faster than those

of the gauze group and the commercial dressing group. Furthermore, grafts prepared with nanober scaffolds were well integrated
into surrounding skin. Fig. 8 shows the changes in wound areas at
different healing times. The wound areas decreased gradually and
reached about 40% and 15% after 21 days for gauze and commercial
dressing groups, respectively. Electrospun nanobers was found to
better than gauze and commercial dressing (p < 0.05) in promoting wound healing. The wound area covered by nanobrous matrix
dropped to approximately 5% at 21 days.
The images of histological examination in Fig. 9 revealed that
PLGA/collagen nanober demonstrated superior wound-healing
effect as compared to gauze and commercial dressing. At 1 week,
there was no discernible difference among histological sections of

3.4. Wound healing and histological examination

In open wound-healing tests, two full-thickness rectangular
wounds were made on the back of each rat. Fig. 7 shows representative animals from each group (gauze, nanobrous matrix, and
commercial dressing) at 1, 2, and 3 weeks after grafting. At 1 week,
wound closure in the PLGA/collagen nanober-covered wounds
was similar to the group that had wounds covered with a commercial dressing. In contrast, at 2 and 3 weeks after surgery the healing

Fig. 8. Wound-healing test of () gauge, () nanobrous matrix (50/50

PLGA/collagen), and () commercial dressing (* p < 0.05). The data are presented as
mean S.D. (N = 4).

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S.-J. Liu et al. / Journal of Membrane Science 355 (2010) 5359

Fig. 9. Histological images of (A) gauze group, (B) 50/50 PLGA/collagen nanober group, and (C) commercial dressing group, at 1 week (left) and 3 weeks (right). (No necrosis
was observed in B3.)

wounds treated by gauze, PLGA/collagen, and commercial dressing

(Figs. 9A1, B1, and C1), all showing ulcerated surface, granulation
tissue formation, and inammatory cell inltration. At 3 weeks
after surgery, the wound treated with PLGA/collagen nanober
(Fig. 9B3) was almost healed, with newly synthesized brous tissue
and sparse inammatory cells in the dermis and subcutis covered by completely re-epithelialized epidermis. On the contrary,
the wounds treated with gauze or commercial dressing showed
incomplete re-epithelialization and prominent inammatory cell
inltration. This further testies that the PLGA/collagen nanobrous membrane could be a suitable tissue-engineering scaffold
for skin regeneration.

4. Conclusions
In the present study, a PLGA/collagen nanobrous matrix
produced by the electrospinning process was introduced for
the application of wound dressing. The diameter of electrospun
nanobers was 250 nm on average and ranged from 150 to 650 nm.
Degradation rate of PLGA/collagen nanobers, cytocompatibility and cellular responses to PLGA/collagen nanobers, cell and
nanober interactions, and open wound healing in rats were
studied. In the cell activity assessment, the electrospun 50/50
PLGA/collagen ratio nanobers exhibited levels of signicance in
cell proliferation during culture. This may be a consequence of the

high surface area available for cell attachment due to their threedimensional features and of the restoration of natural ECM proteins
biological and structural properties. Nanobrous matrices made of
PLGA/collagen were very effective as wound-healing accelerators
in early-stage wound healing.
References
[1] G.D. Warden, J.R. Safe, M. Kravitz, A 2-stage technique for excision and grafting
of burn wounds, J. Trauma 22 (2) (1982) 98103.
[2] H.K. Noh, S.W. Lee, J.M. Kim, J.E. Oh, K.H. Kim, C.P. Chung, S.C. Choi, W.H. Park,
B.M. Min, Electrospinning of chitin nanobers: degradation behavior and cellular response to normal human keratinocytes and broblasts, Biomaterials 27
(2006) 39343944.
[3] B.M. Min, Y. You, J.M. Kim, S.J. Lee, W.H. Park, Formation of nanostructured
poly(lactid-co-glycolid acid)/chitin matrix and its cellular response to normal
human keratinocytes and broblasts, Carbohydr. Polym. 57 (2004) 285292.
[4] C.R. Yoo, I.S. Yeo, K.E. Park, J.H. Park, S.J. Lee, W.H. Park, B.M. Min, Effect of
chitin/silk broin nanobrous bicomponent structures on interaction with
human epidermal keratinocytes, Int. J. Biol. Macromol. 42 (2008) 324334.
[5] W.J. Li, C.T. Laurencin, E.J. Caterson, R.S. Tuan, F.K. Ko, Electrospun nanobrous
structure: a novel scaffold for tissue engineering, J. Biomed. Mater. Res. 60
(2002) 613621.
[6] J.A. Matthews, G.E. Wnek, D.G. Simpson, G.L. Bowlin, Electrospinning of collagen
nanobers, Biomacromolecules 3 (2002) 232238.
[7] H.M. Powell, D.M. Supp, S.T. Boyce, Inuence of electrospun collagen on would
contraction of engineered skin substitutes, Biomaterials 29 (2008) 834843.
[8] K.S. Rho, L. Jeong, G. Lee, B.M. Seo, Y.J. Park, S.D. Hong, S. Roh, J.J. Cho, W.H.
Park, B.M. Min, Electrospinning of collagen nanobers: effects on the behavior
of normal human keratinocytes and early-stage wound healing, Biomaterials
27 (2006) 14521461.

S.-J. Liu et al. / Journal of Membrane Science 355 (2010) 5359

[9] J.P. Chen, G.Y. Chang, J.K. Chen, Electrospun collagen/chitosan nanobrous
membrane as wound dressing, Colloids Surf. A: Physiochem. Eng. Aspect 313314 (2008) 183188.
[10] T.J. Sill, H.A. von Recum, Electrospinning: applications in drug delivery and
tissue engineering, Biomaterials 29 (2008) 19892006.
[11] D.A.D. Parry, A.S. Craig, Collagen bril during development and maturation and
their contribution to the mechanical attributes of connective tissue, in: M.E.
Nimni (Ed.), Collagen, vol. 2, CRC Press, Florida, 1988, pp. 120.
[12] S.N. Park, H.J. Lee, K.H. Lee, H. Suh, Biological characterization of EDCcrosslinked collagen-hyaluronic acid matrix in dermal tissue restoration,
Biomaterials 24 (2003) 16311641.
[13] I.V. Yannas, J.F. Burke, D.P. Orgill, E.M. Skrabut, Wound tissue can utilize a polymeric template to synthesize a functional extension of skin, Science 215 (1982)
174176.
[14] J. Hansbrough, S. Boyce, M. Cooper, T. Forman, Burn would closure with cultured
human keratinocytes and broblasts attached to a collagen-glycosaminoglycan
substrate, J. Am. Med. Assoc. 262 (1989) 21252130.
[15] Y. Yang, X. Zhu, W. Cui, X. Li, Y. Jin, Electrospun composites mats of poly[(d,lladctide)-co-glycolide] and collagen with high porosity as potential scaffolds
for skin tissue engineering, Macromol. Mater. Eng. 294 (2009) 611619.

59

[16] S.G. Kumbar, S.P. Nukavarapu, R. James, L.S. Nair, C.T. Laurencin, Electrospun
poly(lactic acid-co-glycolic acid) scaffolds for skin tissue engineering, Biomaterials 29 (2008) 41004107.
[17] D.F. Williams, Biodegradation of surgical polymers, J. Mater. Sci. 17 (1982)
12331246.
[18] S.A.M. Ali, P.J. Doherty, D.F. Williams, Mechanisms of polymer degradation in
implantable devices. 2. Poly(dl-lactic acid), J. Biomed. Mater. Res. 27 (1993)
14091418.
[19] H. Kobayashi, K. Shiraki, Y. Ikada, Toxicity test of biodegradable polymers by implantation in rabbit cornea, J. Biomed. Mater. Res. 26 (1992)
14631476.
[20] C.S. Chen, M. Mrksich, S. Huang, G.M. Whitesides, D.E. Ingber, Geometric control
of cell life and death, Science 276 (1997) 14251428.
[21] T.G. van Kooten, J.F. Whitesides, A.F. von Recum, Inuence of silicone (PDMS)
surface texture on human skin broblast proliferation as determined by cell
cycle analysis, J. Biomed. Mater. Res. 43 (1998) 114.
[22] T. Nishida, K. Yasumoto, T. Otori, J. Desaki, The network structure of corneal
broblasts in the rat as revealed by scanning electron microscopy, Invest. Ophthalmol. Vis. Sci. 29 (1988) 18871890.