polymers

Article
Physically Crosslinked Hydrogels Based on Poly
(Vinyl Alcohol) and Fish Gelatin for Wound Dressing
Application: Fabrication and Characterization
Teng Ren 1,2 , Jing Gan 3 , Liping Zhou 1 and Hao Chen 1, *
1 Marine College, Shandong University, Wenhua West Road, Gao Strict, Weihai 264209, China;
[email protected] (T.R.); [email protected] (L.Z.)
2 Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and
Nutritional Engineering, China Agricultural University, Beijing 100083, China
3 College of Life Sciences, Yantai University, Yantai 264005, China; [email protected]
* Correspondence: [email protected]; Tel./Fax: +86-0631-568-8079




Received: 19 June 2020; Accepted: 20 July 2020; Published: 2 August 2020


Abstract: We developed the interpenetrating double network composite hydrogel based on poly
(vinyl alcohol) (PVA) and fish gelatin (FG) via thermal treatment and repeated freeze-thawing.
A function of salicylic acid was incorporated into the hydrogel to improve its antibacterial properties.
The color values, water contents, water evaporation rate, and swelling behavior were investigated.
The drug-loading performance of the composite hydrogel was demonstrated by loading salicylic
acid in various hydrogel systems. Moreover, the cumulative dissolution percentage of salicylic acid
and the antibacterial activity of composite hydrogel were carried out. The results revealed that as
FG concentration increased from 0% to 3.75% (w/v), gels changed from white to slight yellow and
the swelling ratio increased from 54% to 83% (within 8 h). The presence of FG decreased the water
content of gels which ranged from 86% to 89% and also decreased water evaporation rate. All gels
presented the swelling index within 0.5–1.0, indicating a non-Fickian diffusion mechanism. The drug
sustained dissolution behavior of pure PVA and composite hydrogel showed the same trend. Besides,
the presence of the obvious bacteriostatic zones means that drug-loaded composite hydrogels have
an effective antibacterial property. These results demonstrated that PVA/FG-based interpenetrating
hydrogel is an appropriate biomaterial for drug-carrying wound dressing application.

Keywords: poly (vinyl alcohol); fish gelatin; salicylic acid; hydrogels; wound dressing

1. Introduction
Nowadays, healthcare-associated infections have caused severe problems in clinicians, with a
large number of people suffering from acute and chronic wounds. Designing new wound dressing
materials has been an imperative issue in modern medical technology findings. Functional active
wound dressings are expected to provide a moist wound environment, offer protection from secondary
infections, remove wound exudate, accelerate tissue regeneration, and improve the efficiency of wound
repair [1]. Many systems such as foams, hydrogels, and films have been developed for wound dressings
in recent years. Among these wound dressing types, hydrogels are the optimal candidates because
they could meet all requirements for wound healings [2].
Hydrogels are three-dimensional cross-linked hydrophilic polymers networks being used for
various biomedical applications. These polymeric materials do not disintegrate in water at physiological
temperature and pH but swell considerably in an aqueous medium because of their cross-linked
structures [3]. Hydrogels possess many advantages such as large water content, soft elasticity,
cooling effect, and so forth [4]. High water content of hydrogels assists to promote granulation

Polymers 2020, 12, 1729; doi:10.3390/polym12081729 www.mdpi.com/journal/polymers

Polymers 2020, 12, 1729 2 of 13

and epithelialization due to the moist environment [5]. The soft elastic property of hydrogels could
provide easy application and removal after wound was healed without any damage [6]. Additionally,
temperature of cutaneous wounds could be lowered by hydrogels providing soothing and cooling
effect [7]. Moreover, hydrogel wound dressings are non-irritant, non-reactive with biological tissue
and permeable to metabolites. At the same time, hydrogels can be exploited as platforms to transport
bioactive molecules e.g., antibiotics, and pharmaceuticals to wound sites [2]. The released drugs play
an active role in the healing process either directly as debriding agents for removing necrotic tissue,
or indirectly as antimicrobial drugs, which prevent infection and aid tissue regeneration [8].
Admittedly, hydrogels are not flawless. Single-network hydrogels have weak mechanical
properties and slow response at swelling. Multicomponent networks are usually designed as
interpenetrating polymer networks to address this drawback [9]. A wide variety of hydrophilic
polymers have been utilized to fabricate hydrogels, including natural polymers (polysaccharides and
proteins) and synthetic polymers containing hydrophilic functional groups such as –COOH, –OH,
–NH2 , and so on [10,11]. Natural polymers e.g., alginate, gelatin, chitosan [12], and synthetic polymers
e.g., polyvinyl alcohol and polyvinyl pyrrolidone [13] have been widely used to fabricate hydrogels
for biomedical applications.
PVA is a hydrophilic, biodegradable, and biocompatible synthetic polymer and has been widely
used in different areas of the biomedical field [14]. PVA molecules would cross-linked physically under
repeated freeze-thawing [15]. Compared with other synthetic polymers, PVA hydrogel possesses
desirable physical properties such as good biodegradability [16], non-toxicity [17], and favorable
mechanical strength [16,18], especially it is relatively cheap in contrast to many other synthetic
polymers. However, single PVA hydrogel exhibits weak mechanical strength and insufficient swelling
properties [19,20], which restrict its utilization as a dressing material [15].
Gelatin is a water soluble and biocompatible polymer, which is produced by partial hydrolysis
of collagen extracted from skin and bones [21]. Among these, gelatin from marine sources such as
fish skin or bone has gained attention as a base material in the biomedical scaffold, food packaging,
and pharmaceutical industry because of its low cost and multi-functionality. FG possesses desirable
properties such as biocompatibility, biodegradability, hydrophilia, and water retaining capacity [20,22].
In addition, FG is deemed as an ideal hemostatic and wound dressing material [23] owing to its good
coagulation effect on platelets which can promote blood coagulation [24] and is also widely used for the
manufacturing of hard and soft capsules, plasma expanders, and in wound care in the pharmaceutical
industry. Thus, FG was elected to blend with PVA, attempting to enhance the mechanical strength and
swelling response of single PVA hydrogel.
The biggest obstacle to wound healing is infections that can lead to systemic complications [25,26].
Sustained delivery of bioactive agents was reported as highly beneficial for wounds. Salicylic
acid is one of the earliest antibacterial and anti-inflammatory drugs. In the current investigation,
a function of salicylic acid was to be incorporated into the hydrogels to protect its antibacterial and
anti-inflammatory properties.
The objective of this work was to obtain interpenetrating polymer network hydrogels based on FG
and PVA using the methods of thermal treatment and repeated freeze-thawing, attempting to modify
the mechanical properties of pure FG hydrogel and the re-swelling performance of pure PVA hydrogel.
The effect of FG concentration on gel properties was investigated. Then salicylic acid was added for
improving the anti-microbial and anti-inflammatory properties, and the release of salicylic acid in vitro
was investigated to analyze the drug-loading performance.

2. Materials and Methods

2.1. Materials
FG with model 100G NET/BAG was a kind gift from Vinh Hoan Collagen Corporation; PVA1977
was obtained from Anhui Weiwei Group Co., Ltd. (Anhui, China); analytical-grade salicylic acid
Polymers 2020, 12, 1729 3 of 13

was supplied by Xilong Scientific Co., Ltd. (Shantou, China); analytical-grade sodium chloride was
purchased from Tianjin Ruijinte Chemical Co., Ltd. (Tianjin, China) All other chemicals are analytical
grade, and without further purification unless otherwise described.

2.2. Preparation of Hydrogel

2.2.1. Preparation of PVA/FG Composite Hydrogel

The PVA/FG composite hydrogels were fabricated by thermal treatment and cyclic freeze-thawing
method [5]. In brief, PVA (10 g) was dissolved in 100 mL deionized water at 90 ◦ C and was magnetically
stirred for 1 h. Proper amounts of FG (0, 0.75, 1.50, 2.25, 3.00, 3.75 g) were then added to the solutions
(80 ◦ C) respectively under magnetic stirring, followed by ultrasonic defoaming for 20 min to remove
the bubbles. Subsequently, proper amounts of these mixtures were poured into Petri dishes, followed
by freezing at −20 ◦ C for 24 h and thawing for 3 h at room temperature for four continuous cycles.
Finally, the PVA/FG composite hydrogels with different FG contents were obtained.

2.2.2. Preparation of Drug-Loaded PVA/FG Hydrogel

PVA/FG mixed solution with 1.50% (w/v) FG and 10% (w/v) PVA was obtained according to
Section 2.2.1. Salicylic acid (0.5%, w/v) was added into the PVA/FG solution at 50 ◦ C under magnetic
stirring (for 2 h). After ultrasonic defoaming for 20 min, the composed solution was poured into the
Petri dish and repeatedly frozen-thawed four times following a procedure outlined in Section 2.2.1 to
obtained the drug-loaded PVA/FG composite hydrogel.

2.3. Characterization of Hydrogels

2.3.1. Measurement of Color Values

The color values of hydrogels with different FG contents were measured by a precision colorimeter
(NR110, Shenzhen Sanenchi technology co., Ltd., Shenzhen, China). The CIE Lab scale chromaticity
parameters L*, a*, b* were recorded respectively. L* denotes the brightness index, L* = 0 means black,
L* = 100 means white; a* denotes red and green, +a* means red and −a* green; b* denotes blue and
yellow, +b* is for yellow and −b* is for blue. The color values can objectively evaluate the magnitude
of the chromatic aberration and its visual difference. The implications of general color values ∆E are
shown in Table 1. ∆E can be calculated by the following equation.
i1/2
∆E = (L∗ − L)2 + (a∗ − a)2 + (b∗ − b)2
h
(1)

where L*, a*, and b* are the color parameter values of hydrogel sample, L, a, and b are the color
parameter values of the control hydrogel (without FG).

Table 1. General color values and their corresponding implications.

Color Values Implications

1.6 < ∆E < 3.2 Cannot distinguish its color difference
3.2 < ∆E < 6.5 A few people can tell the difference in colors
6.5 < ∆E < 13 The color difference is very obvious
13 < ∆E < 25 Most belong to different colors
∆E > 25 Different colors

2.3.2. Determination of Water Content in Hydrogels

The thawing hydrogels were cut into cylinders with a diameter of 3.3 cm using a circular cutter.
Then the samples were gently wiped with filter papers to remove surface water and weighted.
Subsequently, they were dried in an oven (105 ◦ C) to constant weight. The weights of all samples were
Polymers 2020, 12, 1729 4 of 13

recorded as the average value of three measurements. The water content of hydrogel was determined
using the following equation.

M0 − M1
Water content % = × 100% (2)
M0

where M0 and M1 are the weight of the thawed hydrogel and the weight of hydrogel at dry
state, respectively.

2.3.3. Swelling Properties

The hydrogels were cut into cylindrical shaped specimens (3.3 cm in diameter) for drying in an
oven to constant weight. The dried hydrogel samples were then immersed in deionized water and saline
solution (0.90% w/v of NaCl in deionized water) at room temperature respectively. Subsequently these
samples were taken out at the regular time intervals. The excess water on the surfaces of the samples
was removed by blotting gently with filter papers and the samples were weighed immediately [27].
The swelling degree (SD %) was calculated as the following equation:

Mt − M1
SD% = × 100% (3)
M1

where Mt is the weight at interval time t during water absorption, M1 is the initial weight of the
dry gels.

2.3.4. Swelling Kinetic Study

The water absorption character of the hydrogels in pharmaceutics resembles to the swelling of the
hydrogel in polymer science. Generally, the diffusion behavior and transport of small molecules in
polymers have been classified into three clear types [28], which can be distinguished by the shape of
the swelling curve, represented by Equation (4).

Mt − M1
F= = ktn (4)
Me − M1

lnF = lnk + nlnt (5)

where Me is the weight of the swollen hydrogel at equilibrium, Mt is the weight of swollen hydrogel at
interval times, M1 is the weight of dried hydrogel, k is the rate constant characteristic of the hydrogel,
and n is the transfer exponent indicating the mechanism of swelling. According to the value of n,
the diffusion behavior and transport of small molecules in polymers have been classified into three
clear types.
Type 1: The Fickian diffusion, where penetrate diffusion rate is the slowest and hence the diffusion
controlled (n ≤ 0.5).
Type 2: The other extreme, where the segmental relaxation processes are the slowest and hence,
the stress relaxation-controlled mechanism (n = 1).
Type 3: The anomalous diffusion is an intermediate situation when the penetrate mobility and
segmental relaxation are on a comparable time scale (0.5 < n < 1).
Type 1 and type 2 can be regarded as two limiting cases of transport processes with type 3 being
an intermediate case, where both processes are operative in a coupled manner.
The slope value of n represents the swelling exponent. In order to clarify the diffusion process
of water molecules in PVA/FG composite hydrogels, the results of the swelling measurement were
used to calculate by Equations (4) and (5). The slope (n) of the double logarithmic plot of Equation (5)
was calculated. As mentioned above, the value of n indicates the type of transport mechanism. When
n ≤ 0.5, it is Fickian diffusion, when 0.5 < n <1, it is non-Fickian diffusion.
Polymers 2020, 12, 1729 5 of 13

2.3.5. Measurement of Water Evaporation Rate

The pure PVA hydrogel and PVA/FG composite hydrogel were cut into squares of 3 × 3 cm and
then kept in an incubator at 37 ◦ C (relative humidity of 50%) for 24 h. The hydrogels were taken out
and weighed every 2 h until reached the constant weight. The water evaporation rate was calculated
by the following equation:
W0 − Wt
Water lost = × 100% (6)
W0 − Wd
where W 0 , Wt , Wd are, respectively, the initial weight, the measured weight after evaporating for
predetermined time and the final weight of the hydrogels.

2.4. The Estimation of Drug Release In Vitro

To study the release pattern of salicylic acid from the hydrogels, a known weight of salicylic acid
loaded hydrogel was immersed in 400 mL saline and placed in a thermostatic rotary shaker at shaking
speed of 100 rpm at 40 ◦ C. Subsequently the solution (7 mL) was withdrawn at 0, 3, 5, 7, 10, 15, 20, 30,
60, 90, 150 min respectively and equal volume of the same dissolution medium was added back to
maintain a constant volume. The amount of salicylic acid released from the hydrogel was determined
by UV-visible spectrophotometer at 290 nm and calculated from a previously calibrated standard curve.
All release experiments were conducted in triplicate.

2.5. Antibacterial Activity Test

The antibacterial efficacy of the salicylic acid-encapsulated hydrogel against E. coli (ATCC25922,
Gram-positive) and S. aureus (CMCC (B) 26003, Gram-negative) was evaluated according to the
inhibition zone. Sterile physiological saline was used to prepare various bacterial species into a
suspension with a concentration of 1 × 106 –1 × 107 CFU/mL and the concentration of bacteria was
determined by a UV/VIS spectrometer (T6 new century, Beijing Puxi General Instrument Co., Ltd.,
Beijing, China) at 625 nm. Afterwards, 0.1 mL inoculums containing approximately 106–107 CFU/mL
of tested bacteria were seeded on the surface of the solid LB media (1% tryptone, 0.5% yeast extract, 1%
agar, and 1% NaCl, sterilization at 120 ◦ C for 20 min). Finally, the salicylic acid-encapsulated hydrogels
were cut into a disc form with a 6-mm diameter mold and then placed on the LB plates. The plates
were incubated at 37 ◦ C for 24 h before the diameters of inhibitory zones were measured.

2.6. Statistical Analysis

All the analyses were carried out at least triplicates to find mean and standard deviation values
and the results were expressed as a mean ± standard deviation. Figures were generated with Origin 8.5.

3. Results and Discussion

3.1. Sensory Characteristics of Hydrogels

The photographs of PVA/FG composite hydrogels with a function of FG contents are shown in
Figure 1. All samples exhibited good formability. As FG concentration ranged from 0% to 3.00% (w/v),
the gels showed exceptional uniformity because of the mutual compatibility of FG and PVA molecules.
While as to the composite hydrogel containing 3.75% (w/v) FG, FG particles could be clearly figured out
on the surface of the hydrogel. This could be attributed to the over-saturated compatibility between
PVG and FG molecules at this concentration. Hence, they failed to form a uniform composite hydrogel.
The colors of the composite hydrogels with a function of FG contents are shown in Figure 2.
Owing to the color of light yellow in FG particles, the color of PVA/FG composite hydrogels gradually
turned to yellow with the increasing amount of FG. Since 6.5 < ∆E < 13 denotes the distinguished color
is quite obvious and 13 < ∆E < 25 means that the tested samples belong to different colors. It could
be concluded that the FG contents showed great influences on the color of composite gels. When the
Polymers 2020, 12, x FOR PEER REVIEW 6 of 13

Polymers 2020, 12, 1729 6 of 13

FG content is less than 2.25%, the color differences of PVA/FG composite hydrogels are not obvious.
It can be Figure 1. Images
considered thatof the PVA/FG
these composite
hydrogels hydrogel
have the with different
same color. When the fishFG
gelatin (FG)iscontents.
content between 2.25%
and 3.75%, the color difference of the gel can be clearly seen, and as the FG content exceeds 3.75%,
The colors
the composite of the composite
hydrogel displays a hydrogels
completelywith a function
different color. of FG contents are shown in Figure 2.
Polymers
Owing2020, 12,color
to the x FORofPEER REVIEW
light yellow in FG particles, the color of PVA/FG composite hydrogels gradually 6 of 13

turned to yellow with the increasing amount of FG. Since 6.5 < ΔE < 13 denotes the distinguished
color is quite obvious and 13 < ΔE < 25 means that the tested samples belong to different colors. It
could be concluded that the FG contents showed great influences on the color of composite gels.
When the FG content is less than 2.25%, the color differences of PVA/FG composite hydrogels are not
obvious. It can be considered that these hydrogels have the same color. When the FG content is
between 2.25% and 3.75%, the color difference of the gel can be clearly seen, and as the FG content
exceedsFigure
3.75%,1.the composite hydrogel displays a completely different color.
Images of the PVA/FG composite hydrogel with different fish gelatin (FG) contents.
Figure 1. Images of the PVA/FG composite hydrogel with different fish gelatin (FG) contents.

(A) colors of the composite hydrogels with a function

The (B) of FG contents are shown in Figure
a* 2.
80 L* 0.00
Owing to the color of light yellow in FG particles, the color of PVA/FG composite hydrogels gradually
turned to yellow with the increasing amount of FG. Since 6.5 < ΔE < 13 denotes the distinguished
color is quite
75 obvious and 13 < ΔE < 25 means that the tested samples belong to different colors. It
could be concluded that the FG contents showed great influences on the color of composite gels.
-1.00
When the FG content is less than 2.25%, the color differences of PVA/FG composite hydrogels are not
70
L*

obvious. It can be considered that these hydrogels have the same color. When the FG content is
a*

between 2.25% and 3.75%, the color difference of the gel can be clearly seen, and as the FG content
65
exceeds 3.75%, the composite hydrogel displays a completely different color.
-2.00

(A) 60 (B) a*
80 0.00 1.00 2.00 3.00 L* 4.00 0.00 0.00 1.00 2.00 3.00 4.00
FG content（%） FG content（%）

(C) 75 (D) ΔE
b*
0.50 16.00
-1.00
70 14.00
0.00
L*

a*

12.00
-0.50
10.00
65
-1.00 -2.00
8.00
ΔE
b*

-1.50 6.00
60
-2.00 0.00 1.00 2.00 3.00 4.00 4.00 0.00 1.00 2.00 3.00 4.00
FG content（%） 2.00 FG content（%）
-2.50
0.00
(C) 0.00 1.00 2.00 3.00 4.00 (D) 1.00 2.00 3.00 ΔE
4.00
b*
FG content (%) 16.00 FG content (%)
0.50
14.00
Figure 2. Effects
0.00 2.
Figure Effects of
of FG
FG contents
contents on
on the
the color
color of
of PVA/FG
PVA/FG composite
composite hydrogels (A) L*,
hydrogels(A) (B) a*,
L*,(B) (C) b*,
a*,(C) b*,and
and
(D) ∆E, (10% PVA).
(D) ΔE, (10% PVA). 12.00
-0.50
10.00
3.2. The-1.00
Water Content of Hydrogels
3.2. The Water Content of Hydrogels 8.00
ΔE
b*

The water
-1.50 content of PVA/FG hydrogels with a function
6.00 of FG amounts is presented in Figure 3.
The water content of PVA/FG hydrogels with a function of FG amounts is presented in Figure
The water content of the pure PVA hydrogel was 89.2%, with the increase of FG content, the water
4.00
3. The -2.00
water content of the pure PVA hydrogel was 89.2%, with the increase of FG content, the water
content of the composite hydrogel decreased, but these differences 2.00
were not significant, and the water
content of the composite hydrogel decreased, but these differences
-2.50 were not significant, and the water
content of PVA/FG composite hydrogels still ranged from 86.0% to 88.8%. There are the two possible
content of PVA/FG composite hydrogels still ranged 0.0086.0% to 88.8%. There are the two possible
from
reasons for all0.00 1.00 hydrogels
composite 2.00 exhibiting
3.00 4.00
desirable 1.00
water retention 2.00 The PVA
ability. 3.00 molecule
4.00 was
abundant of hydroxyl groups which
FG content (%) could easily form hydrogen bonds FGwith
contentwater
(%) molecules and
retain water molecules [21]. FG also exhibited strong hydrophilicity owing to a mass of hydrophilic
Figure 2. Effects of FG contents on the color of PVA/FG composite hydrogels (A) L*, (B) a*, (C) b*, and
groups of FG proteins such as carboxyl groups, amino groups, and hydroxyl groups. Consequently,
(D) ΔE, (10% PVA).

3.2. The Water Content of Hydrogels

The water content of PVA/FG hydrogels with a function of FG amounts is presented in Figure
3. The water content of the pure PVA hydrogel was 89.2%, with the increase of FG content, the water
 Polymers 2020, 12, x FOR PEER REVIEW 7 of 13

reasons for all composite hydrogels exhibiting desirable water retention ability. The PVA molecule
was abundant of hydroxyl groups which could easily form hydrogen bonds with water molecules
and 2020,
Polymers retain water molecules [21]. FG also exhibited strong hydrophilicity owing to a mass
12, 1729 7 of 13 of
hydrophilic groups of FG proteins such as carboxyl groups, amino groups, and hydroxyl groups.
Consequently, compared with pure PVA hydrogel, the obtained composite hydrogels still have good
compared with purethey
water retention, PVAwere
hydrogel, theofobtained
capable retainingcomposite hydrogels
enough water still have
molecules [20].good water retention,
they were capable of retaining enough water molecules [20].

90.00 Water content

89.00
Water content (%)

88.00

87.00

86.00

85.00
0.00 0.75 1.50 2.25 3.00 3.75
FG content (%)

Figure 3. Water content of different PVA/FG composite hydrogels (10% PVA).

Figure 3. Water content of different PVA/FG composite hydrogels (10% PVA).
3.3. Swelling Behavior Analysis
3.3. Swelling Behavior Analysis
One essential property of wound dressing material is good hydration capacity which facilitates
One essential
rapid wound healingproperty of wound
and proceeds dressing material
to improve is good hydration
the re-epithelialization capacity
process which
[29]. facilitates
Therefore,
rapid wound
evaluation healing
of swelling and proceeds
capacity of hydrogelto improve
is of greatthe re-epithelialization
significance. process [29].
This characteristic Therefore,
indicates the
evaluation
capabilities ofof swelling fluids
absorbing capacityandofexudates
hydrogel[30].is ofThe
great significance.
swelling This of
behaviors characteristic
hydrogels in indicates
distilledthe
capabilities
water as well asofinabsorbing fluids
normal saline and
were exudates
studied. [30].4A,B
Figure The displays
swellingthebehaviors
swellingof hydrogels
properties of in distilled
PVA/FG
water aswith
hydrogels welldifferent
as in normal saline
ratios of FG inwere studied.
distilled waterFigure 4A,B displays
and normal the swelling
saline respectively. properties of
Noteworthily,
thePVA/FG
swellinghydrogels
properties with differentwere
of hydrogels ratios of FG in
enhanced by distilled water
the presence and Furthermore,
of FG. normal saline therespectively.
swelling
Noteworthily, the swelling properties of hydrogels were enhanced by
property was improved steadily as FG concentration increased. The increased swelling ratio occurred the presence of FG.
Furthermore,
because of the highthesolubility
swellingofproperty
FG in water was improved
[31]. steadily
Additionally, as FG
the PVA andconcentration
FG moleculesincreased.
cross-linkedThe
increased
each other and swelling
formedratio occurred because
interpenetrating double of network
the high gelation
solubilityunder
of FGthese
in water [31]. Additionally,
processes, which wouldthe
PVA
bring and the
about FG molecules cross-linked each
denser microstructure. As a other
result,and
moreformed interpenetrating
capillary structure could double network
be formed gelation
to retain
under [5,24,32,33].
moisture these processes, which would bring about the denser microstructure. As a result, more
capillary structureofcould
A comparison be formed
swelling degreetoofretain
PVA/FGmoisture hydrogel (10% PVA + 1.5% FG) in
[5,24,32,33].
composite
A comparison
physiological saline andof distilled
swelling water
degreeisof PVA/FG
shown composite
in Figure hydrogel
4C. The PVA/FG (10% PVA + 1.5%
composite FG) in
hydrogel
physiological
showed saline
slight larger and distilled
swelling ratio inwater is shown
distilled in Figure
water than 4C. The PVA/FG
in physiological composite
saline. This phenomenonhydrogel
mayshowed slightbylarger
be caused swellingosmotic
the different ratio in pressure
distilled water than in
of medium inphysiological saline. This
which the composite phenomenon
hydrogel was
may [29].
placed be caused by the pressure
The osmotic different of
osmotic pressuresaline
physiological of medium in which
was higher the composite
than distilled water,hydrogel
so the rate was
of placed
diffusion[29].
of The
waterosmotic pressure
molecules intoofthe
physiological
hydrogel insaline was higher
physiological thanwas
saline distilled
slower water,
thanso thein
that rate
of diffusion
distilled water. of water molecules into the hydrogel in physiological saline was slower than that in
distilled water.
 Polymers2020,
Polymers 12,x1729
2020,12, FOR PEER REVIEW 88of
of13
13

A
100

80

Swelling ratio (%)

60

40 FG0.00%
FG0.75%
20 FG1.50%
FG2.25%
FG3.00%
0
0 1 2 3 4 5 6 7 8 9
Time (h)

B
100

80
Swelling ratio (%)

60

40
FG0.00%
FG0.75%
20 FG1.50%
FG2.25%
FG3.00%
0
0 1 2 3 4 5 6 7 8 9
Time (h)

C
80

60
Swelling Ratio（%)

40

Normal saline
20 Distilled water

-1 0 1 2 3 4 5 6 7 8 9
Time（h）

Swellingratio
Figure4.4.Swelling
Figure ratio of
of PVA/FG
PVA/FG composite
composite hydrogel
hydrogel (PVA
(PVAcontent
contentisis10%)
10%)inindistilled
distilledwater
water(A), in
(A),
physiological saline (B) and a comparison of swelling degree of composite hydrogel (10%
in physiological saline (B) and a comparison of swelling degree of composite hydrogel (10% PVA + PVA + 1.5%
FG) in
1.5% FG)distilled waterwater
in distilled and physiological salinesaline
and physiological (C). (C).
Polymers 2020, 12, 1729 9 of 13

3.4. Polymers 2020, 12, x FOR Rate

Water Evaporation PEER REVIEW
Analysiss 9 of 13

Moist
3.4. environment
Water can promote
Evaporation Rate Analysiss wound healing, and clinical wound dressings need to be replaced
repeatedlyMoist environment can [5],
before recovering as a result,
promote wound the water
healing, andevaporation
clinical woundrate dressings
of wound dressing
need to be is of
importance. The hydrogel
replaced repeatedly beforedressings
recoveringwith smaller
[5], as a result,water evaporation
the water evaporationrate can
rate of reduce the replacing
wound dressing
times
is leading to quicker
of importance. The healing,
hydrogel less pain, and
dressings withgreat costwater
smaller savings [34]. Therate
evaporation water
can evaporation
reduce the rate
of pure PVA hydrogel
replacing and PVA/FG
times leading to quickercomposite hydrogel
healing, less pain, is shown
and greatincost
Figure 5. The
savings water
[34]. The loss
waterof pure
evaporation rate of pure PVA hydrogel and PVA/FG composite hydrogel is shown
PVA hydrogel was 84.38% in 24 h while the composite hydrogels was 81.05%. This result could be in Figure 5. The
waterto
ascribed loss of pure
that PVA hydrogel
the addition of FGwas 84.38% the
increased in 24crosslinking
h while the composite hydrogels
density, led wasnetwork
to denser 81.05%. This
structure
result could be ascribed to that the addition of FG increased the crosslinking density, led to denser
and smaller pores of hydrogel eventually [35]. The results show that the PVA/FG composite hydrogel
network structure and smaller pores of hydrogel eventually [35]. The results show that the PVA/FG
has a better water evaporation rate than the pure FG gel, so that PVA/FG composite hydrogel is more
composite hydrogel has a better water evaporation rate than the pure FG gel, so that PVA/FG
suitable as a wound dressing compared with pure FG hydrogel.
composite hydrogel is more suitable as a wound dressing compared with pure FG hydrogel.

Figure
Figure 5. 5. Waterevaporation
Water evaporation rate
rate of
ofpure
purePVA
PVAhydrogel
hydrogeland PVA/FG
and composite
PVA/FG hydrogel.
composite hydrogel.

3.5. 3.5.
Swelling Kinetics
Swelling Kinetics

TheThe solvent
solvent diffusion
diffusion into
into thethe hydrogelnetwork
hydrogel network is
is not
not passive
passive diffusion
diffusioninto
intothe
thevoid
voidspaces of of the
spaces
the network
network but includes
but includes a concomitant
a concomitant stretching
stretching of the
of the network
network segments
segments bybyadvancing
advancing solvent
solvent front,
front,
which which
results in results in the plasticization
the plasticization of the material
of the material with change
with a large a large change in the volume
in the volume of the [24].
of the sample
sample [24]. The swelling kinetics parameters of PVA/FG composite hydrogels with different FG
The swelling kinetics parameters of PVA/FG composite hydrogels with different FG contents in distilled
contents in distilled water and physiological saline are shown in Table 2. All the values of the
water and physiological saline are shown in Table 2. All the values of the correlation coefficient, R2 ,
correlation coefficient, R2, were above 0.99, and with the increase of FG concentration, the values of
wereswelling
above 0.99, and with
exponent the increase
n decreased of FG
(but not lessconcentration,
than 0.5). This the valuesthe
indicated of swelling process of nwater
diffusion exponent decreased
(butmolecules
not less than 0.5). This indicated the diffusion process of water
in PVA/FG composite hydrogels was non-Fickian diffusion [24,32]. molecules in PVA/FG composite
hydrogels was non-Fickian diffusion [24,32].
Table 2. n values (swelling exponent) for composite hydrogels at various FG contents in distilled
water
Table 2. nand normal
values saline (PVA
(swelling content
exponent) foris composite
10%). hydrogels at various FG contents in distilled water
and normal saline (PVA content is 10%). Distilled Water Normal Saline
FG Content (%)
Distilled n Water R2 n R2
Normal Saline
FG Content (%) 0.00 0.6028 0.9977 0.6130 0.9986
0.75 n R2
0.5832 0.9991
n
0.5795 0.9997 R2
0.00 1.500.6028 0.5631 0.99770.9996 0.5444 0.6130
0.9998 0.9986
0.75 2.250.5832 0.9991 0.5795
0.5454 0.9990 0.5276 0.9999 0.9997
1.50 3.000.5631 0.9996 0.5444
0.5255 0.9999 0.5141 0.9999 0.9998
2.25 0.5454 0.9990 0.5276 0.9999
3.00 0.5255 0.9999 0.5141 0.9999
 Polymers 2020, 12, x FOR PEER REVIEW 10 of 13
Polymers 2020, 12, 1729 10 of 13

3.6. In Vitro Salicylic Acid Release

3.6. InSalicylic
Vitro Salicylic
acid asAcida Release
model drug was chosen for delivery in this study. The effect of FG
concentration
Salicylic acid as a model drugacid
on the salicylic releasefor
was chosen behaviors
delivery infrom hydrogel
this study. was of
The effect investigated under
FG concentration
physiological saline. In vitro cumulative release profiles of salicylic acid
on the salicylic acid release behaviors from hydrogel was investigated under physiological saline. from pure PVA hydrogel
(10%
In vitroPVA) and PVA/FG
cumulative release composite hydrogel
profiles of salicylic(1.5% FG + pure
acid from 10% PVA) are exhibited
PVA hydrogel (10%inPVA)
Figure 6. PVA/FG
and As seen,
these two kinds of hydrogel systems showed obvious burst release
composite hydrogel (1.5% FG + 10% PVA) are exhibited in Figure 6. As seen, these two kinds in the initial 30 min, with slowlyof
releasing systems
hydrogel in the following
showed2.5 h. The burst
obvious release percentage
release in theofinitial
pure 30 PVA min,hydrogel and PVA/FG
with slowly hydrogel
releasing in the
were 33.67%
following and
2.5 h. 33.63%
The releaserespectively
percentageinofthe first
pure PVA0.5 hydrogel
h, and 45.10% and 46.41%
and PVA/FG respectively
hydrogel in the and
were 33.67% first
1 h. After 3 h, the cumulative release of the composite hydrogel was slightly
33.63% respectively in the first 0.5 h, and 45.10% and 46.41% respectively in the first 1 h. After 3 h,higher than pure PVA
hydrogel,
the cumulativewhich was consistent
release with the
of the composite changewas
hydrogel of swelling state of
slightly higher thepure
than composite hydrogel.
PVA hydrogel, This
which
result showed that the PVA hydrogel with 1.5% FG exhibited no significant
was consistent with the change of swelling state of the composite hydrogel. This result showed that the differences in the
cumulative release. It could be inferred that 1.5% FG exerted little influence
PVA hydrogel with 1.5% FG exhibited no significant differences in the cumulative release. It could be on the drug release
behavior.
inferred The
that reasons
1.5% for thelittle
FG exerted above phenomena
influence on themaydrugberelease
that the salicylicThe
behavior. acid was not
reasons forchemically
the above
attached to the polymer and the only interactions were intermolecular
phenomena may be that the salicylic acid was not chemically attached to the polymer and attraction and entrapment
the only
within the polymer
interactions matrix. Thus,
were intermolecular the drug
attraction andrelease largely
entrapment depended
within on thematrix.
the polymer swelling process
Thus, and
the drug
three-dimensional polymer network [32].
release largely depended on the swelling process and three-dimensional polymer network [32].

80
70
60
Dissolution percentage（%）

50
40
30
Pure hydrogel
20
Composite hydrogel
10
0
-10
-20 0 20 40 60 80 100 120 140 160
Time（min）
Figure 6. In vitro salicylic acid release profile of pure PVA hydrogel and PVA/FG composite hydrogel
Figure
(1.5% 6. In
FG) in vitro
normalsalicylic
saline.acid release profile of pure PVA hydrogel and PVA/FG composite hydrogel
(1.5% FG) in normal saline.
3.7. Antibacterial Activity
3.7. Antibacterial Activity
Antibacterial activity is an important property of hydrogel dressings. We evaluated the antibacterial
Antibacterial
activity activity ishydrogels
of PVA/FG composite an important
loadedproperty
with 0.5%ofsalicylic
hydrogelaciddressings.
by observingWetheevaluated the
range of the
antibacterial activity of PVA/FG composite hydrogels loaded with 0.5% salicylic acid by
zone of inhibition. From the photos shown in Figure 7, the presence of the obvious bacteriostatic zone observing
the range of
represents thecomposite
that zone of inhibition.
hydrogelsFrom the photos
encapsulated shown
with in Figure
salicylic 7, the presence
acid exhibited good of the obvious
antimicrobial
bacteriostatic
activity againstzone representsbacteria
Gram-positive that composite
(S. aureushydrogels
CMCC (B)encapsulated with salicylicbacteria
26003) and Gram-negative acid exhibited
(E. coli
good antimicrobial
ATCC activityaverage
25922). The largest againstdiameters
Gram-positive bacteria zone
of inhibition (S. aureus
were CMCC
even 17(B)mm.26003) and Gram-
Consequently,
negative
the PVA/FGbacteria (E. coli
composite ATCC 25922).
hydrogel The largest
encapsulated with average
salicylic diameters of inhibition
acid has good zoneeffect
antibacterial wereand
evencan17
mm.
be Consequently,
used the PVA/FG composite hydrogel encapsulated with salicylic acid has good
as a wound dressing.
antibacterial effect and can be used as a wound dressing.
Polymers 2020, 12, 1729 11 of 13
Polymers 2020, 12, x FOR PEER REVIEW 11 of 13

Figure 7.
Figure 7. Inhibitory
Inhibitory effect against E.
effect against E. coli
coli (A),
(A), S.
S. aureus
aureus (B).
(B).

4. Conclusions
thisresearch,
In this research, PVA/FG
PVA/FG interpenetrating
interpenetrating polymer
polymer network
network hydrogels
hydrogels were synthesized
were synthesized by thermalby
thermal treatment
treatment and cyclicand cyclic freeze-thawing
freeze-thawing method and method and
salicylic salicylic
acid releaseacid release
test was usedtest was used to
to demonstrate
demonstrate
the excellent in thevitro
excellent in vitrobehavior
drug release drug release behavior
of PVA/FG of PVA/FG
composite composite
hydrogels. The FGhydrogels. The FG
content showed
content showed
significant significant
influences on the influences on the apparent
apparent characteristics, characteristics,
color values, swellingcolor values,
ratio, water swelling ratio,
evaporation
waterand
rate, evaporation rate, andof
swelling kinetics swelling
PVA/FG kinetics of PVA/FG
composite hydrogel composite hydrogelthat
and discovered andthediscovered
dose of FGthatwas
the
dosekey
the of FG wasinthe
factor key factor
obtaining in obtaining
PVA/FG PVA/FG
hydrogels withhydrogels with desirable
desirable properties. properties.the
Additionally, Additionally,
composite
the composite
hydrogels hydrogels
exhibited highexhibited
capabilityhigh capabilityfluid
in absorbing in absorbing
based onfluid based onbehavior.
the swelling the swelling Thebehavior.
study of
Theswelling
the study ofkinetics
the swelling kinetics
revealed revealed
that the thatprocess
swelling the swelling process of hydrogel
of the composite the composite
was nothydrogel was
influenced
notthe
by influenced
addition by the addition
of FG. The results of of
FG. inThe results
vitro modelofdrug
in vitro model
salicylic drug
acid salicylic
release showedacidthat
release showed
the PVA/FG
that the PVA/FG
composite hydrogelscomposite hydrogelsrelease
had good sustained had good sustained
property. release
Moreover, property. Moreover,
the antibacterial activity testthe
of
antibacterial
PVA/FG activity
hydrogels test of PVA/FG
showed their good hydrogels showed
antibacterial their
effect. Asgood antibacterial
a result, the PVA/FG effect. As a result,
hydrogels the
showed
PVA/FG hydrogels
excellent showed excellent
physical properties, which met physical properties,
the essential which metfor
requirements theideal
essential requirements
medical for
applications.
ideal medical
Thus, applications.
it is a potential wound Thus, it is awith
dressing potential wound
excellent dressing
forming andwith excellent
physical forming and physical
properties.
properties.
Author Contributions: Conceptualization, T.R. and H.C.; formal analysis, J.G.; funding acquisition, H.C.;
investigation, L.Z.; methodology, T.R.; project administration, H.C.; software, J.G.; supervision, T.R. and H.C.;
Author Contributions: Conceptualization, T.R. and H.C.; formal analysis, J.G.; funding acquisition, H.C.;
visualization, J.G. and L.Z.; writing—original draft, T.R. and L.Z.; writing—review and editing, T.R. All authors
investigation,
have read and L.Z.;
agreemethodology, T.R.;
to the published projectofadministration,
version the manuscript.H.C.; software, J.G.; supervision, T.R. and H.C.;
visualization, J.G. and L.Z.; writing—original draft, T.R. and L.Z.; writing—review and editing, T.R. All authors
Funding: This work was financially supported by Natural Science Foundation of Shandong Province
have read and agree to the published version of the manuscript.
(No. ZR2019BC053), Beijing Food Nutrition and Human Health High Precision Innovation Center Open Fund
(No. 20171014),
Funding: Chinawas
This work Postdoctoral
financiallyScience Foundation
supported (No.Science
by Natural 2017M612281) andof
Foundation China Postdoctoral
Shandong ProvinceScience
(NO.
Special Foundation (No.2018T110693).
ZR2019BC053), Beijing Food Nutrition and Human Health High Precision Innovation Center Open Fund (No.
Acknowledgments: We thank Jiajun
20171014), China Postdoctoral ScienceXian (Octogone
Foundation (Guangzhou)
(No. Trading
2017M612281) Co., Limited)
and China for his
Postdoctoral assistance
Science to
Special
supply FG. (No.2018T110693).
Foundation
Conflicts of Interest: The authors declare no conflict of interest.
Acknowledgments: We thank Jiajun Xian (Octogone (Guangzhou) Trading Co., Limited) for his assistance to
supply FG.
References
Conflicts of Interest: The authors declare no conflict of interest with respect to the authorship and/or publication
1.
of thisLiu, H.; Wang, C.Y.; Li, C.; Qin, Y.G.; Wang, Z.H.; Yang, F.; Li, Z.H.; Wang, J.C. A functional chitosan-based
article.
hydrogel as a wound dressing and drug delivery system in the treatment of wound healing. RSC Adv. 2018,
8, 7533–7549. [CrossRef]
Polymers 2020, 12, 1729 12 of 13

2. Kamoun, E.A.; Kenawy, E.R.S.; Chen, X. A review on polymeric hydrogel membranes for wound dressing
applications: PVA-based hydrogel dressings. J. Adv. Res. 2017, 8, 217–233. [CrossRef] [PubMed]
3. Pal, K.; Banthia, A.K.; Majumdar, D.K. Preparation and characterization of polyvinyl alcohol-gelatin hydrogel
membranes for biomedical applications. Aaps Pharmscitech 2007, 8. [CrossRef] [PubMed]
4. Dhivya, S.; Padma, V.V.; Santhini, E. Wound dressings—A review. Biomedicine-Taiwan 2015, 5, 24–28.
[CrossRef]
5. Fan, L.H.; Yang, H.; Yang, J.; Peng, M.; Hu, J. Preparation and characterization of chitosan/gelatin/PVA
hydrogel for wound dressings. Carbohydr. Polym. 2016, 146, 427–434. [CrossRef]
6. Gonzalez, J.S.; Maiolo, A.S.; Hoppe, C.E.; Alvarez, V.A. Composite gels based on Poly (vinyl alcohol) for
biomedical uses. Proc. Mat. Sci. 2012, 1, 483–490. [CrossRef]
7. Bullock, A.J.; Pickavance, P.; Haddow, D.B.; Rimmer, S.; MacNeil, S. Development of a calcium-chelating
hydrogel for treatment of superficial burns and scalds. Regen. Med. 2010, 5, 55–64. [CrossRef]
8. Broughton, G.; Janis, J.E.; Attinger, C.E. A brief history of wound care. Plast. Reconstr. Surg. 2006, 117, 6S–11S.
[CrossRef]
9. Dragan, E.S. Design and applications of interpenetrating polymer network hydrogels. A review. Chem. Eng. J.
2014, 243, 572–590. [CrossRef]
10. Ullah, F.; Othman, M.B.H.; Javed, F.; Ahmad, Z.; Akil, H.M. Classification, processing and application of
hydrogels: A review. Mater. Sci. Eng. C Mater. Biol. Appl. 2015, 57, 414–433. [CrossRef]
11. Hamedi, H.; Moradi, S.; Hudson, S.M.; Tonelli, A.E. Chitosan based hydrogels and their applications for
drug delivery in wound dressings: A review. Carbohydr. Polym. 2018, 199, 445–460. [CrossRef]
12. Kumar, P.T.S.; Lakshmanan, V.K.; Anilkumar, T.V.; Ramya, C.; Reshmi, P.; Unnikrishnan, A.G.; Nair, S.V.;
Jayakumar, R. Flexible and Microporous Chitosan Hydrogel/Nano ZnO Composite Bandages for Wound
Dressing: In Vitro and In Vivo Evaluation. ACS Appl. Mater. Interfaces 2012, 4, 2618–2629. [CrossRef]
[PubMed]
13. Razzak, M.T.; Darwis, D. Irradiation of polyvinyl alcohol and polyvinyl pyrrolidone blended hydrogel for
wound dressing. Radiat. Phys. Chem. 2001, 62, 107–113. [CrossRef]
14. Jiang, S.; Liu, S.; Feng, W.H. PVA hydrogel properties for biomedical application. J. Mech. Behav. Biomed. Mater.
2011, 4, 1228–1233. [CrossRef] [PubMed]
15. Kamoun, E.A.; Chen, X.; Eldin, M.S.M.; Kenawy, E.R.S. Crosslinked poly (vinyl alcohol) hydrogels for wound
dressing applications: A review of remarkably blended polymers. Arab. J. Chem 2015, 8, 1–14. [CrossRef]
16. Sonker, A.K.; Rathore, K.; Teotia, A.K.; Kumar, A.; Verma, V. Rapid synthesis of high strength
cellulose-poly(vinyl alcohol) (PVA) biocompatible composite films via microwave crosslinking. J. Appl.
Polym. Sci. 2019, 136. [CrossRef]
17. Ahmadian, Y.; Bakravi, A.; Hashemi, H.; Namazi, H. Synthesis of polyvinyl alcohol/CuO nanocomposite
hydrogel and its application as drug delivery agent. Polym. Bull. 2019, 76, 1967–1983. [CrossRef]
18. Tanan, W.; Panichpakdee, J.; Saengsuwan, S. Novel biodegradable hydrogel based on natural polymers:
Synthesis, characterization, swelling/reswelling and biodegradability. Eur. Polym. J. 2019, 112, 678–687.
[CrossRef]
19. Gao, T.L.; Jiang, M.H.; Liu, X.Q.; You, G.J.; Wang, W.Y.; Sun, Z.H.; Ma, A.G.; Chen, J. Patterned Polyvinyl
Alcohol Hydrogel Dressings with Stem Cells Seeded for Wound Healing. Polymers 2019, 11, 171. [CrossRef]
20. Hago, E.E.; Li, X.S. Interpenetrating Polymer Network Hydrogels Based on Gelatin and PVA by Biocompatible
Approaches: Synthesis and Characterization. Adv. Mater. Sci. Eng. 2013. [CrossRef]
21. Mahnama, H.; Dadbin, S.; Frounchi, M.; Rajabi, S. Preparation of biodegradable gelatin/PVA porous scaffolds
for skin regeneration. Artif. Cells Nanomed. Biotechnol. 2017, 45, 928–935. [CrossRef] [PubMed]
22. Chen, L.; Cheng, H.H.; Xiong, J.; Zhu, Y.T.; Zhang, H.P.; Xiong, X.; Liu, Y.M.; Yu, J.; Guo, Z.X. Improved
Mechanical Properties of Poly (butylene succinate) Membrane by Co-electrospinning with Gelatin. Chin. J.
Polym. Sci. 2018, 36, 1063–1069. [CrossRef]
23. Xing, Q.; Yates, K.; Vogt, C.; Qian, Z.C.; Frost, M.C.; Zhao, F. Increasing Mechanical Strength of Gelatin
Hydrogels by Divalent Metal Ion Removal. Sci. Rep. 2014, 4, 4706. [CrossRef] [PubMed]
24. Rathna, G.V.N.; Chatterji, P.R. Swelling kinetics and mechanistic aspects of thermosensitive interpenetrating
polymer networks. J. Macromol. Sci. Pure Appl. Chem. 2001, 38, 43–56. [CrossRef]
Polymers 2020, 12, 1729 13 of 13

25. Zhu, Y.N.; Zhang, J.M.; Song, J.Y.; Yang, J.; Xu, T.; Pan, C.; Zhang, L. One-step synthesis of an antibacterial
and pro-healing wound dressing that can treat wound infections. J. Mater. Chem. B 2017, 5, 8451–8458.
[CrossRef] [PubMed]
26. Cao, Z.N.; Luo, X.G.; Zhang, H.; Fu, Z.; Shen, Z.; Cai, N.; Xue, Y.A.; Yu, F.Q. A facile and green strategy
for the preparation of porous chitosan-coated cellulose composite membranes for potential applications as
wound dressing. Cellulose 2016, 23, 1349–1361. [CrossRef]
27. Oliveira, R.N.; McGuinness, G.B.; Ramos, M.E.T.; Kajiyama, C.E.; Thire, R. Properties of PVA Hydrogel
Wound-Care Dressings Containing UK Propolis. Macromol. Symp. 2016, 368, 122–127. [CrossRef]
28. Wang, T.; Zhu, X.K.; Xue, X.T.; Wu, D.Y. Hydrogel sheets of chitosan, honey and gelatin as burn wound
dressings. Carbohydr. Polym. 2012, 88, 75–83. [CrossRef]
29. Varaprasad, K.; Mohan, Y.M.; Vimala, K.; Raju, K.M. Synthesis and Characterization of Hydrogel-Silver
Nanoparticle-Curcumin Composites for Wound Dressing and Antibacterial Application. J. Appl. Polym. Sci.
2011, 121, 784–796. [CrossRef]
30. Kokabi, M.; Sirousazar, M.; Hassan, Z.M. PVA-clay nanocomposite hydrogels for wound dressing.
Eur. Polym. J. 2007, 43, 773–781. [CrossRef]
31. Kamoun, E.A.; Kenawy, E.R.S.; Tamer, T.M.; El-Meligy, M.A.; Eldin, M.S.M. Poly (vinyl alcohol)-alginate
physically crosslinked hydrogel membranes for wound dressing applications: Characterization and
bio-evaluation. Arab. J. Chem. 2015, 8, 38–47. [CrossRef]
32. Wen, X.; Cao, X.L.; Yin, Z.H.; Wang, T.; Zhao, C.S. Preparation and characterization of konjac
glucomannan-poly (acrylic acid) IPN hydrogels for controlled release. Carbohydr. Polym. 2009, 78,
193–198. [CrossRef]
33. Chen, X.L.; Chen, Q.H.; Yan, T.T.; Liu, J.K. Characterization of konjac glucomannan-gelatin IPN physical
hydrogel scaffold. IOP Conf. Ser. Mater. Sci. Eng. 2017, 207, 012029. [CrossRef]
34. Huang, Y.C.; Chu, H.W.; Huang, C.C.; Wu, W.C.; Tsai, J.S. Alkali-treated konjac glucomannan film as a novel
wound dressing. Carbohyd. Polym. 2015, 117, 778–787. [CrossRef]
35. Hwang, M.R.; Kim, J.O.; Lee, J.H.; Kim, Y.I.; Kim, J.H.; Chang, S.W.; Jin, S.G.; Kim, J.A.; Lyoo, W.S.;
Han, S.S.; et al. Gentamicin-loaded wound dressing with polyvinyl alcohol/dextran hydrogel: Gel
characterization and In Vivo healing evaluation. AAPS Pharmscitech 2010, 11, 1092–1103. [CrossRef]

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