Macromolecular Research, Vol. 22, No. 2, pp 131-138 (2014) www.springer.

com/13233
DOI 10.1007/s13233-014-2023-z pISSN 1598-5032 eISSN 2092-7673

Fabrication of Poly(ethylene oxide) Hydrogels for Wound Dressing

Application Using E-Beam

Haryanto1, SeongCheol Kim*,1, Jeong Hwan Kim2, Jong Oh Kim2, SaeKwang Ku3,
Hyunkug Cho4, Do Hung Han4, and PilHo Huh5
1
Department of Advanced Organic Materials Engineering, Yeungnam University, Gyeongbuk 712-749, Korea
2
College of Pharmacy, Yeungnam University, Gyeongbuk 712-749, Korea
3
College of Oriental Medicine, Daegu Hanny University, Gyeongbuk 712-715, Korea
4
School of Chemical Engineering, Yeungnam University, Gyeongbuk 712-749, Korea
5
Department of Polymer Science & Engineering, Pusan National University, Pusan 609-735, Korea

Received May 21, 2013; Revised September 5, 2013; Accepted October 5, 2013

Abstract: Cross-linked poly(ethylene oxide) (PEO) hydrogel was developed for application to wound dressings. To
determine the optimum conditions for wound dressing materials, PEO with different molecular weights and various
PEO/poly(ethylene glycol) diacrylate (PEGDA) compositions were irradiated in order to obtain cross-linked hydro-
gels using an electron beam with various beam intensities. The contents of the PEGDA influenced the gel fraction,
swelling ratio, mechanical properties, and water vapor transmission rate. To evaluate the healing effect of PEO/
PEGDA cross-linked hydrogel for wound dressing, wounds on the backs of mice were covered with PEO/PEGDA
hydrogel films. Healing under the wet environment of the hydrogel dressing was faster than with a gauze control
and a commercial reference. The results demonstrate the possibility of the facile production of mechanically robust
and transparent wound dressing materials with improved wound healing characteristics.
Keywords: crosslinked hydrogel, electron beam, mechanical properties, wound dressing.

Introduction delivery systems.3-5 Hydrogel dressing consists of insoluble

polymers with a high water content making them an ideal
Wound dressing is usually used to encourage the various dressing to facilitate autolytic debridement of necrosis and
stages of wound healing and create better conditions for slough.6 The hydrogel-type wound dressings can be formed
healing. They often cover the wound surface in order to by crosslinking of water soluble polymers such as polyvinyl
accelerate its healing. The powdery hydrogel materials gen- alcohol, polyvinyl pyrolidone, polyacrilic acid, and poly(ethyl-
erally introduced to an open, draining wound in order to ene oxide) (PEO).7 Among water soluble polymers above,
absorb the exudate from the wound.1 A drawback of such PEO shows the merit of its relatively low toxicity.8,9 How-
hydrogel material is that the dry material can tend to clump ever, the pure PEO hydrogel has low mechanical strength
and form lumps prior to and during introduction of the and it is very fragile.10 Poly(ethylene glycol) diacrylate (PEGDA)
material to the wound site. Clumping can also occur after is a nontoxic, water soluble, and flexible polymer, which has
introduction of the material to the wound site. In addition, polymerizable end groups.11 PEGDA hydrogels are an attrac-
removal of lumps from the wound site without damaging tive potential scaffold system for tissue-engineered heart
the new tissue is difficult. Dressing should be easy to apply, valves (TEHVs) because they are not only cytocompatible and
be painless on removal, should create an optimal environ- modifiable but can also withstand bending deformations.12
ment for wound healing, and should require fewer dressing The biocompatible chitosan/poly(ethylene glycol) diacry-
changes, thereby reducing nursing time.2 Therefore, the hydro- late blend films were succesfully prepared by Michael addition
gel having better mechanical strength is expected to be bet- reaction as a potential wound dressing material which shows no
ter for use as a dressing material. cytotoxicity toward growth of L929 cell and had good in vitro
In recent years, significant attention has been focused on biocompatibility.11 Therefore it is expected that co-crosslink-
research and development of polymer hydrogels as bioma- ing of PEO with PEGDA with an e-beam irradiation can
terials, such as contact lenses, wound dressing, and drug increase the mechanical strength and modulate other physical
properties by increasing the crosslink density.
*Corresponding Author. E-mail: sckim07@ynu.ac.kr Physical, chemical, and radiation methods can be applied

The Polymer Society of Korea 131

 Haryanto et al.

to preparation of the crosslinked polymer hydrogels. Among oven at 55 oC for 24 h, and then remaining moisture was
them, radiation techniques γ-ray13 and electron beam14 are removed in a vacuum oven for 6 h at the same temperature.
relatively simple for improvement or modification of poly- Dry PEO films were sealed in an evacuated polyethylene
meric materials through cross-linking, grafting, and degra- bag, followed by irradiation at various doses (100, 150, 200,
dation reactions.15 However, the e-beam irradiation method 250, and 300 kGy) using an electron beam (EB) having a
is more advantageous because the radiation dose can be eas- beam current of 5 and 10 mA with an energy of 0.7 MeV
ily controlled and the experimental condition is straight for- generated from an Electron Beam Accelerator.
ward for mass production of products and also the product Determination of Gel Fraction. Immediately after irra-
is free from unwanted chemical impurities such as residues diation, the seal was opened and the weight of the dry PEO
from initiators, retarders, and/or accelerators for initiation film sample (2 cm×2 cm) was measured accurately. After that,
and for manipulation of the crosslinking reaction in chemical the crosslinked PEO film was placed in distilled water at
crosslinking methods. Moreover, the degree of crosslinking 50 oC for 24 h for removal of the soluble parts. The insolu-
and grafting can be controlled by controlling the radiation ble gel obtained was dried in the oven at 50 oC for 24 h and
dose.16 When the e-beam is irradiated on a polymer film, many then in a vacuum oven at 50 oC for 6 h in order to obtain a
free radicals are generated on the polymer backbone of PEO, as constant dry weight. The gel fraction was determined from
the main component in a polymer blend film. The radicals the weight ratio between the insoluble dry gel weight and
attack the double bonds of PEGDA to polymerize and finally the initial weight of the polymer,
crosslink the PEGDA and PEO or the radicals undergo the
Gel fraction (%) = (Wc/Wo)×100
chain scission reaction which reduces the molecular weight of
polymer. At high temperature the viscosity of polymer is Where Wc and Wo are the weight of insoluble dry gel and the
low, therefore, the radical has enough mobility to find the initial weight of a dry film.18
double bonds or another radical to make crosslinking reac- Determination of Swelling Ratio. The known weight of
tion before the decay of radicals causing chain scission.17 the crosslinked dry PEO film (2 cm×2 cm) was soaked in
In this article, we demonstrate the possibility of mass pro- distilled water at room temperature. The weight of the swollen
duction of the mechanically robust PEO hydrogel wound gel was measured at specific time intervals after removal of
dressing with water permeability similar to that of a natural excessive surface water using filter papers. The procedure
skin of human bodies. was repeated until there was no further weight increase. The
swelling ratio (SR) was calculated using the following equation:
Experimental SR (%) = (Wt/Wo)×100
Materials. Poly(ethylene oxide) (PEO) and poly(ethylene Where Wt and Wo are the weight of swollen gel at time t and
glycol) diacrylate (PEGDA) were purchased from Sigma- that of the dry PEO film, respectively.10
Aldrich, St. Louis, USA. Determination of the Percentage Increase of the Size.
Animals. Male Sprague-Dawley (SD) rats weighting 250- The pieces of dry crosslinked PEO film (2 cm×2 cm) was
280 g were purchased from Oreint Bio (Seongnam, Korea). soaked in distilled water at room temperature until the film
All rats received food and water at a temperature of 20-23 oC reach constant length (cm) of PEO gel. The PEO hydrogel
and a relative humidity of 50±5% for 24 h prior to the experi- was placed on a glass plate and then the length (cm) of PEO
ments. The rats were housed singly to prevent fighting and gel was measured. The following equation was used for cal-
atack the wound. All animal procedures were performed culation of percentage increase of the size (IS):
according to the Guiding Principles in the Use of Animals
IS (%) = (L-Lo)/Lo×100
in Toxicology, as adopted in 2008 by the Society of Toxicol-
ogy (20). The protocols for the animal studies were approved Where L and Lo are the length of swollen gel at an equilib-
by the Institute of Laboratory Animal Resources of Yeung- rium state and that of the dry PEO film.
nam University. Determination of Water Vapor Transmission Rate. The
Preparation of Hydrogel. Poly(ethylene glycol) diacrylate water vapor transmission rate was measured using JIS 1099A
(PEGDA) (Mn=700) and various molecular weights of poly standard test methods.20,29 A round piece of crosslinked dry
(ethylene oxide) (PEO), Mn=2×105, 4×105, 6×105 were used PEO film was mounted on the mouth of a cup with a diame-
for preparation of the hydrogel. Aqueous solution of PEO ter of 7 cm containing 50 g CaCl2 and placed in an incubator
(8% w/w) was prepared by stirring the solution at room of 90% RH at 40 oC. The water vapor transmission rate
temperature for 24 h. The composition of PEGDA/PEO was (WVTR) was determined as follows:
changed from 0/100, 2.5/100, 5/100, 7.5/100, and 10/100
WVTR (g m-2h-1) = ((W2-W1)/S)
(w/w), respectively. The calculated amount of aqueous solu-
tion was poured into a petri dish to formdry PEO film with a where W1 and W2 are the weight of the whole cup at the first
thickness of 0.3 mm. The PEO solution was dried in the and the second hours, respectively, and S is the transmitting

132 Macromol. Res., Vol. 22, No. 2, 2014

 Fabrication of Poly(ethylene oxide) Hydrogels for Wound Dressing Application Using E-Beam

area of the sample. number of microvessels in granulation tissues (vessels/mm2

Mechanical Properties. The tensile strength and Young’s of field), number of infiltrated inflammatory cells in granu-
modulus of crosslinked PEO/PEGDA hydrogel films were lation tissues (cells/mm2 of field), percentages of collagen
measured using a tensile test machine (Instron 4464,UK). occupied region in granulation tissues (%/mm2 of field), and
The hydrogels were cut into a dumbbell shape and the mechani- granulation tissue areas (mm2/crossly trimmed central regions
cal properties were measured with a constant extension rate of wounds) were measured on prepared crossly trimmed indi-
of 50 mm/min, at room temperature.21 vidual histological skin samples using a digital image analyzer
In vivo wound healing assay. To evaluate efficacy of in (DMI-300, DMI, Korea) according to previously described
vivo wound healing, twenty one male Sprague-Dawley rats methods.23,24 The histopathologist was blind to group distri-
weighing 250~280 g were selected as an animal model. The bution when this analysis was performed. In addition, re-
rats were devided in 3 group, 7 rats in each group. The oper- epithelization rates were also calculated according to some
ation was performed under the cocktail of two anesthetics, modification, as follows:26
Zoletil 50® (tiletamine/zolazepam) and Rompun® (Xylazine
hydrochloride), which were purchased from Virbac S.A. Re-epithelization (%)
and Bayer, by IP injection.22 prior to the operation, the dorsal Total length of wound (10 mm)
hair of rats was removed using an electric razor. Subsequently, - Desquamated epithelium regions (mm)
back skin was excised for development of two full thickness = Total length of wound ×100
wounds (1.5 cm×1.5 cm). Each wound was treated with gauze
(control), reference product (Medifoam H®, Ildong Pharm, Statistical Analysis. A multiple comparison tests for dif-
Co., Korea) or test material (PEO/PEGDA dressing sheet), ferent dose groups was performed. The Levene test was used
respectively. All materials were covered and fixed with the for examination of variance homogeneity.27 If results of the
elastic adhesive tape, Micropore® (3M), and replaced with Levene test indicated no significant deviations from vari-
new ones at the proper time. Every rat was cared for in detached ance homogeneity, the obtained data were analyzed by one
cages and digital images of the sites were collected every way ANOVA test followed by least-significant differences
three days using a digital camera. These macroscopic data were (LSD) multi-comparison test in order to determine which
utilized for measurement of the size reduction and the epi- pairs of group comparison were significantly different. In
thelizing rate using Adobe Acrobat 9 Professional®.22-24 Size the case of significant deviations from variance homogeneity
reduction and epithelializing rate (%) were calculated as observed on the Levene test, a non-parametric comparison
follows: test, Kruskal-Wallis H test was performed. When a signifi-
cant difference was observed in the Kruskal-Wallis H test,
W
Size reduction (%) = ------t × 100 the Mann-Whitney U (MW) test was performed in order to
W0
determine the specific pairs of group comparison, which are
Et significantly different. Statistical analyses were performed
- × 100
Epithelializing Rate (%) = ---------------
W t + Et using SPSS for Windows.28 In addition, changes between
gauze control and test material treated groups were calcu-
where Et=Epithelized area on time ‘t’, Wt=Wounded area on lated in order to help the understanding of the efficacy of
time ‘t’ and W0=Wounded area at initial time. Multiple com- test materials, as follows.
parisons test was performed for statistical clarification of
differences between the groups. One way ANOVA test followed Percentage changes compared with gauze control (%)
by the LSD method was used for analysis of the acquired Data of tested group-Data of gauze control
data. = Data of gauze control ×100
Histological Process. Full thickness wounded samples of
skin were collected containing dermis and hypodermis, and Results and Discussion
they were crossly trimmed one part/sample based on the wounds,
if possible central regions. All trimmed skins were fixed in Effect of Dose Rates on the Gel Fraction and Swelling
10% neutral buffered formalin. After paraffin embedding, Properties. Figure 1(a) shows the effect of irradiation dose
sections measuring 3-4 μm were prepared. Representative rate on the gel fraction of the e-beam irradiated polymer.
sections were stained with Hematoxylin and Eosin (H&E) The gel fraction showed a steady increase, from 0.21at 100 kGy
for light microscopic examination or Masson’s trichrome to 0.59 at 300 kGy dose rate. The radicals are generally pro-
for collagen fibers.22,25 Thereafter, the histological profiles duced as a result of an indirect effect of radiation and result
of individual skin were observed under a light microscope in crosslinking and scission reaction of polymer chains
(E400, Nikon, Japan). when the polymer films are irradiated with high doses of
Histomorphometry. For more detailed observation of histo- radiation. The swelling ratio decreases from 3567% to 1013%
pathological changes, desquamated epithelium regions (mm), with increasing dose rate from 100 kGy to 300 kGy due to

Macromol. Res., Vol. 22, No. 2, 2014 133

 Haryanto et al.

Figure 1. Effect of dose rate on (a) gel fraction, (b) swelling ratio, and (c) percentage increase of the size for PEO 200,000 Mn.

Figure 2. Effect of molecular weight on (a) gel fraction, (b) swelling ratio, and (c) percentage increase of the size.

the increase of the crosslink density, as shown in Figure 1(b). molecular weight may have increased physical crosslink due
All films swelled rapidly in water and reached equilibrium to the radical coupling in the polymer chains. The swelling
within 10 min, except for 100 kGy dose rate, which reached ratio decreases from 1013% with 200,000 MW to 800% with
equilibrium around 60 min. This result demonstrated that 400,000 MW and then decrease slightly to 780% at 600,000
the structure with the low crosslink density could sustain MW. On the other hand, Figure 1(b) showed that the swell-
much water within the gel structure, as expected from equa- ing ratio decreases very significantly from 3567% to 1013%
tion.29 The percentage increase of the size (IS) decreased with increasing dose rate from 100 to 300 kGy. It showed that
with increasing dose rates. The percentage increase of the the swelling ratio is more influenced by irradiation dose
size was 120%, which was obtained at 300 kGy, as shown at than by the molecular weight of PEO.
Figure 1(c). According to the result above, the maximum gel fraction
Effect of Molecular Weight on the Gel Fraction and and the minimum swelling ratio were reached at a dose rate
Swelling Properties. The influence of the molecular weight of 300 kGy with the molecular weight of 400,000. However,
on the gel fraction is shown in Figure 2(a). It shows that the when the molecular weight of PEO increased, the dissolu-
higher the molecular weight of PEO, the higher the gel frac- tion of PEO in distilled water was very poor due to increased
tion was. The gel fraction showed a significant increase viscosity. Therefore, medium molecular weight of PEO
from 59% at 200,000 MW to 66% at 400,000 MW and then (400,000) was used to make PEO and PEO/PEGDA film
just increase slightly to 69% at 600,000 MW. The effect of for further experiments.
the molecular weight of PEO on swelling ratio and percent- Effect of PEGDA Content on Gel Fraction and Swell-
age increase of the size is shown in Figure 2(b) and Figure ing Properties. A small amount of PEGDA was added to
2(c).The swelling ratio and percentage increase of the size the PEO in order to increase the mechanical strength of the
showed a significant decrease as the molecular weight of e-beam crosslinked PEO. Figure 3(a) shows the gel fraction
PEO increased from 200,000 to 400,000. Further decrease of PEO/PEGDA hydrogel. The result showed that the gel
of the swelling ratio and percentage increase of the size was fraction increased almost linearly with increasing the weight
observed with the molecular weight of 600,000, however, percentage of the PEGDA in a mixture. The swelling ratio
the decrease was reduced. The reason for different swelling of PEO/PEGDA hydrogel film with various compositions
ratio and percentage increase of the size with different molecu- as a function of swelling time is shown in Figure 3(b). It
lar weight may be explained as follows: although the radical shows that all of the hydrogel films absorb water very rapidly
density in irradiated PEO film is the same, the film with higher and reach an equilibrium weight within 10 min. The swell-

134 Macromol. Res., Vol. 22, No. 2, 2014

 Fabrication of Poly(ethylene oxide) Hydrogels for Wound Dressing Application Using E-Beam

Figure 3. Effect of content of PEGDA on (a) gel fraction, (b) swelling ratio, and (c) percentage increase of the size.

ing ratio decreased with the increasing content of PEGDA, from a wound at an optimal rate. The rate for normal skin is
and the equilibrium swelling ratio of the crosslinked hydro- 8.5 gm-2h-1, while that for injured skin can range from 11.6
gel films decreased from 771% in the film without the pres- gm-2h-1.31 Therefore, the ideal wound dressing should have a
ence of PEGDA to 310% in that with 10% of PEGDA. The WVTR similar or greater than 11.6 gm-2h-1. The WVTR of
result indicated that the higher content of PEGDA can decrease the PEO/PEGDA hydrogel was close to the ideal value for
the water absorption capacity of PEO/PEGDA hydrogel due wound dressing.
to the crosslinking of PEGDA together with radicals in PEO Effect of PEGDA Content on Mechanical Properties.
backbones via radical polymerization. Furthermore, PEGDA The tensile strength of PEO/PEGDA wet hydrogel film as a
also enhanced the crosslinking reaction of the PEO/PEGDA function of the PEGDA content is shown in Figure 5(a). It
film owing to reduced viscosity, which can enhance the cou- can be seen that the tensile strength of PEO/PEGDA hydro-
pling reaction of radicals before the radical decays into an gel increased exponentially with increasing PEGDA content
unreactive species.The percentage increase of the size declines due to the increased crosslink density and reached the maxi-
from 105% with pure PEO film to 58% with PEO/PEGDA
containing 10% of PEGDA, as shown in Figure 3(c).
Effect of PEGDA Content on Water Vapor Transmission
Rate (WVTR). The effect of the content of PEGDA on the
WVTR of the hydrogel is shown in Figure 4. The figure
shows that the WVTR value is almost constant for all com-
positions of PEGDA because most of the matrix is PEO.
The average WVTR was 19 gm-2h-1 for 2.5%-10% of PEGDA,
however, that of pure PEO was somewhat lower, 15.89 gm-2h-1.
When the value of WVTR is too high, the wound can dry
rapidly, resulting in scars. In addition, if the value is too low
to accumulate exudates, the healing process can be retarded,
resulting in increased risk of bacterial growth.30 Use of an
ideal dressing is known to control evaporation of water

Figure 5. (a) Tensile strength of PEGDA/PEO as a function of

Figure 4. Effect of content of PEGDA on water vapor transmis- PEGDA content and (b) Young’s modulus of PEGDA/PEO films
sion rate. as a function of PEGDA content.

Macromol. Res., Vol. 22, No. 2, 2014 135

 Haryanto et al.

Figure 6. Representative macroscopic data of wounds treated with gauze control, reference and test material on day 0, 3, 6, 9, 12, and 15,
respectively.

mum value (0.48 MPa) with 10% of PEGDA, of which strength whereas the reference and the test material exhibited a moist
was10 times higher than that of the pure PEO (0.044 MPa). surface. On the sixth postoperative day, reference and test
Figure 5(b) shows the Young’s modulus of the PEGDA/ material-applied wounds showed enhanced size reduction.
PEO films. The Young’s modulus increased even more rap- However, the gauze-applied wounds showed lower size
idly with the increasing content of PEGDA. reduction. After the 12th postoperative day, considerable clo-
In vivo Wound Healing. All animals survived until the sure of wounds was discovered in the reference and the test
sacrifice and there was no evidence for necrosis of epider- material-applied wounds, whereas comparatively large expo-
mal tissue. Slight inflammation and bleeding were detected sure was still detected in gauze-applied wounds (p<0.05,
throughout the experiment. Each representative macroscopic Figure 7). In addition, the trend of enhanced epithelization
data on wounds is shown in Figure 6 on the third postopera- was observed mainly in the reference and test material-
tive day, highly severe inflammation was detected in every applied groups. In the same way, both epithelizing rates of
group of wounds. In particular, hemorrhage was accompa- the test material and the reference were significantly (p<0.01 or
nied in the wounds to which sterile gauze only was applied. p<0.05) higher than that of gauze control (Figure 8). The
In addition, the control group showed a dry surface and scabs, test material and the reference displayed equivalent wound-

Figure 7. Size reduction (%) profiles of gauze control (■), refer- Figure 8. Epithelizing rate (%) profiles of gauze control (■), ref-
ence (▲), and test material (●). *; p<0.05 as compared with gauze erence (▲ ), and test material (●). *; p<0.05 as compared with gauze
control group. control group, †; p<0.01 as compared with gauze control group.

136 Macromol. Res., Vol. 22, No. 2, 2014

 Fabrication of Poly(ethylene oxide) Hydrogels for Wound Dressing Application Using E-Beam

Table I. Histomorphometrical Values

Material Applied Groups
Histomorphometry Gauze Control
Reference Test Material
a
Desquamated Epithelium Region (mm) 4.54±1.12 2.40±0.90 1.05±1.08ac
Re-Epithelization (%) 54.61±11.16 75.96±9.04a 89.47±10.84ac
In Granulation Tissues
Microvessels Number 120.43±35.88 51.29±11.48d 21.43±7.89de
Infiltrated Inflammatory Cell Number 403.86±114.92 206.86±27.73d 68.43±8.56de
Collagen Occupied Region (%) 34.14±3.99 49.05±5.81a 64.47±6.64ab
Granulation Tissue Area (mm2) 64.32±10.05 39.90±5.19a 27.61±5.23ab
Values are expressed as Mean±S.D. of seven rat wounds. p<0.01 as compared with gauze control by LSD test. p<0.01 and cp<0.05 as com-
a b

pared with reference by LSD test. dp<0.01 as compared with gauze control by MW test. ep<0.01 as compared with reference by LSD test.

healing effects in both size reduction and epithelizing rate

and showed significantly improved efficacy, compared with
gauze control.
Histopathological Analyses. The histomorphometrical
changes on the full thickness wounds of rat dorsal back skin-
desquamated epithelium regions, re-epithelization, number
of microvessels (neovascularization), infiltrated inflamma-
tory cells and percentages of collagen occupied regions in
granulation tissues, granulation tissue areas are shown in
Table I, and the representative histological profiles of the
experimental groups are shown in Figure 9, respectively. In
histopathological and histomorphometrical comparison with
gauze control, significant (p<0.01) decreases of desqua-
mated epithelial regions were detected in both reference and
test material-applied groups. The number of microvessels
(equal to neovascularization) and inflammatory cells infil-
trated in granulation tissues, and granulation tissue area
itself showed a remarkable (p<0.01) decrease in the refer- Figure 9. The representative histopathological profiles of full thick-
ence and the test material-applied wounds, as compared ness skin wounds (granulation tissues) of gauze control (A~C),
with gauze control, and significantly (p<0.01) increased reference (D~F) and test material (G~I) applied rats. Note that re-
collagen fibers were also observed in the reference and the epithelization - decreases of desquamated epithelial regions, was
test material-applied skin samples. In addition, the re-epi- more extendedly observed in reference and test material applied
thelization rate showed significant (p<0.01) improvement in wound as compared with gauze control wound, respectively. The
both. Impressively, more favorable accelerating efficacy on inflammatory cell infiltrations and neovascularization (arrows) in
the full-thickness wounds was observed in test material-applied granulation tissues (B, E, H) in reference and test material treated
rats. In particular, according to histopathological observa- groups were also less than that of gauze control, and more numerous
tions, significantly (p<0.01 or p<0.05) more rapid regenera- collagen proliferations (C, F, I; green colors) were detected in the
both reference and test material applied groups as compared with
tion of wounds, more rapid reconstruction of granulation
gauze control, respectively. These wound healing signs were more
tissues (decreases of granulation tissues and increase of re-
rapidly occurred in test material applied wounds than those of
epithelization rates), lower inflammatory cell infiltration, and reference, in this experiment. DE, dermis; EP, regenerated epithe-
lower neovascularization were detected in test material- lium; LP, lamina propria. Scale bars=160 μm.
treated wounds, as compared with reference-treated wounds.
In addition, more favorable collagen fiber regeneration was
demonstrated in the test material-applied wounds and the Conclusions
percentage of acollagen occupied region in the test material-
applied wounds was also significantly (p<0.01) enhanced, The PEO/PEGDA hydrogel prepared by e-beam irradiation
as compared to that of the reference-treated wounds (Table I was nontoxic and biocompatible with high mechanical strength.
and Figure 9). The PEO/PEGDA hydrogel contained no toxic ingredients

Macromol. Res., Vol. 22, No. 2, 2014 137

 Haryanto et al.

due to the absence of any organic inhibitor, accelerator, and 456 (2008).
inorganic catalyst. Moreover, the hydrogel had a water vapor (12) C. A. Durst, M. P. Cuchiara, E. G. Mansfield, J. L. West, and
transmission rate similar to that of skin, which could main- K. J. Grande-Allen, Acta Biomater., 7, 2467 (2011).
tain a moist environment on the interface of the wound and (13) Y. N. Sang, C. N. Young, and H. H. Seung, Macromol. Res.,
dressing in order to speed up the healing process. Results of 12, 219 (2004).
(14) K. M. Salmawi and S. M. Ibrohim, Macromol. Res., 19, 1029
in vivo study implied that the test material (PEO/PEGDA)
(2011).
has very favorable wound healing effects; size reduction
(15) J. M. Rosiak and P. Ulanski, Radiat. Phys. Chem., 55, 139
and epithelizing rate acceleration. In addition, PEO/PEGDA
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hydrogel film was able to successfully create amicable envi- (16) A. C. Mesquita, M. N. Mori, and L. G. A. Silva, Radiat. Phys.
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thelization and normalization of wounded sites. These findings Wohrmann B. V., Netherlands, 1992.
were considered direct evidence that PEO/PEGDA hydro- (18) M. Wu, B. Bao, F. Yoshii, and K. Makuuchi, J. Radioanal.
gel film definitely facilitated the wound healing. Therefore, the Nucl. Chem., 250, 391 (2001).
results confirmed the possibility of commercializing robust (19) M. H. Huang and M. C. Yang, Int. J. Pharm., 346, 38 (2008).
PEO/PEGDA gel type wound dressings using e-beam irra- (20) ASTM Standard E96/E96-10, Standard Test Methods for Water
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Acknowledgment. This research was supported by Basic (21) M. T. Razzak, D. Darwis, Zainuddin, and Sukirno, Radiat. Phys.
Chem., 62, 107 (2001).
Science Research Program through the National Research
(22) K. Hirose, H. Onishi, M. Sasatsu, K. Takeshita, K. Kouzuma,
Foundation of Korea (NRF) funded by the Ministry of Edu-
K. Isowa, and Y. Machida, Biol. Pharm. Bull., 30, 2406 (2007).
cation, Science and Technology (20110008342). (23) M. R. Hwang, J. O. Kim, J. H. Lee, Y. I. Kim, J. H. Kim, S.
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