RESEARCH ARTICLE

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Gelatin-Based Versus Alginate-Based Hydrogels: Providing

Insight in Wound Healing Potential
Oana Maria Ionescu, Arn Mignon, Manon Minsart, Jasper Van Hoorick,
Ioannis Gardikiotis, Irina-Draga Caruntu, Simona Eliza Giusca, Sandra Van Vlierberghe,*
and Lenuta Profire*

wounds, including highly exuding wounds

Wound dressings under the form of films constituted of modified alginate such as leg ulcers and burns as well as their
(methacrylated alginate – AlgMA) versus a gelatine derivative containing comorbidities, to exceed £ 5 billion annu-
norbornene functionalities (GelNB) are developed and evaluated for their ally in the United Kingdom.[2,3] Wound care
moisturizing effects, followed by further in vivo testing to assay their wound nowadays mostly requires the use of ad-
vanced wound dressings. Several commer-
healing potential. The gel fraction results shows that AlgMA and GelNB films
cial wound dressings exist based on nat-
displayed a high crosslinking efficiency while the swelling assay reveals a ural polymers such as alginate (Alg) (e.g.,
stronger water uptake capacity for AlgMA films compared to GelNB and to Kaltostat, Algosteril, Carboflex) and gelatine
commercial dressing AquacelAg, used as positive control. Referring to the in (Gel) (Duoderm, Granuflex, Tegasorb).[4]
vivo wound healing effect, the GelNB films not only exhibit proper healing Commercial dressings based on Alg or
Gel are especially interesting because they
properties, yet is higher to the AquacelAg, while the AlgMA films exhibit
have the ability to absorb large amounts
similar wound healing effect as the positive control. On a microscopic level, of exudate,[5,6] are nonadhesive and are
the healing phases (from inflammation to proliferation and contraction) are biocompatible.[7,8] However, the physical in-
present for both materials, yet at a faster rate for the GelNB films, which is in tegrity of these dressings is often limited.
line with the macroscopic findings. These results provide data which support Alg is a water-soluble polysaccharide ex-
that GelNB films outperform AlgMA films, but both can be used for wound tracted from the cell walls of brown al-
gae. It is a copolymer of mannuronic
healing applications.
and guluronic acid, which is covalently
linked in varying blocks. Commercially,
it is available as a sodium salt (NaAlg).
Alg use in commercial wound dressings is based on NaAlg or
1. Introduction ionically crosslinked by combining with multivalent cations such
as Ca2+ .[7,9,10] These physical gels exhibit some drawbacks due
Wound healing is an elaborate and dynamic process which re-
to their limited stability and the possible exchange of the di-
mains an ever-increasing healthcare problem.[1] Although this
valent ions with monovalent ions in the surrounding media.[7]
has witnessed increased progress during the past decades,
The gelation mechanism is also difficult to control.[7] By incor-
the National Health Service (NHS) estimates the cost to treat
poration of methacrylate functionalities, Alg can be modified

O. M. Ionescu, L. Profire A. Mignon

Department of Pharmaceutical Chemistry Smart Polymeric Biomaterials
Faculty of Pharmacy Campus Group T
“Grigore T. Popa” University of Medicine and Pharmacy of Iasi Surface and Interface Engineered Materials
16 University Street, Iasi 700115, Romania KU Leuven, Andreas Vesaliusstraat 13, Leuven 3000, Belgium
E-mail: lenuta.profire@umfiasi.ro I. Gardikiotis
A. Mignon, M. Minsart, J. Van Hoorick, S. Van Vlierberghe Advanced Centre of Research and Development in Experimental
Polymer Chemistry and Biomaterials Group Medicine
Centre of Macromolecular Chemistry “Grigore T. Popa” University of Medicine and Pharmacy of Iasi
Department of Organic and Macromolecular Chemistry 16 University Street, Iasi 700115, Romania
Ghent University I.-D. Caruntu, S. E. Giusca
Krijgslaan 281, S4-bis, Ghent 9000, Belgium Department of Morphofunctional Sciences
E-mail: sandra.vanvlierberghe@ugent.be Faculty of Medicine
“Grigore T. Popa” University of Medicine and Pharmacy of Iasi
16 University Street, Iasi 700115, Romania
The ORCID identification number(s) for the author(s) of this article
can be found under https://doi.org/10.1002/mabi.202100230
DOI: 10.1002/mabi.202100230

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to form Methacrylated-alginate (AlgMA) which allows covalent (Antwerp, Belgium). Gel type B, isolated from bovine hides by
crosslinking.[11,12] The concomitant increased stability together an alkaline treatment was provided by Rousselot (Ghent, Bel-
with the strong swelling and hemostatic properties render Al- gium). Wistar rats were purchased from the Cantacuzino Insti-
gMA an interesting material to function as wound dressing. tute, Romania. The controls, AquacelAg were made at Convatec
Gel is a purified protein which is extracted from animal-derived and Mölnlycke. Ethanol, formalin, isoflurane, hematoxylin, and
collagen and acts as a biomaterial, known for its excellent bio- eosin were bought from Merck Company. Normal saline (0.9%
compatibility and cell-interactive properties due to the presence m/v) was purchased from B. Braun, Germany and Help (sterile
of Arg-Gly-Asp motives in its backbone. However, while this ma- cotton gauze) was produced by Jiangsu Jiele Medical Dessing Co.,
terial forms a hydrogel at room temperature, it dissolves at phys- Ltd, China.
iological conditions due to the loss of the triple helices which
are based on interchain hydrogen bonds.[13] Gel thus mimics
the natural extracellular matrix and may be considered as a vi- 2.1.1. Development of AlgMA Films
able option to provide a suitable wound healing environment,
by developing a covalently crosslinked hydrogel network result- The modification of NaAlg was performed as earlier described.[21]
ing from chemical modifications.[13] Many modifications have In brief, 4 equivalent of methacrylic anhydride with respect to
already been reported to date. However, a versatile strategy is the amount of alcohol functionalities were added dropwise to a
to introduce photo-crosslinkable functionalities based on thiol- 2% wt/) solution of NaAlg in demineralized water, while continu-
ene chemistry as they provide spatiotemporal control and associ- ously monitoring and adjusting the pH to 8 using a 5 m NaOH so-
ated straightforward processing.[13–15] One of the most common lution. After 24 h reaction at room temperature, purification was
chemical modifications consists of introducing chain growth- performed by dialysis (molar mass cut off 12–14 kDa) in dem-
polymerizable MA functionalities.[14] However, besides this of- ineralized water for 72 h, changing the dialysis bath twice daily.
ten reported strategy, thiol-ene photochemistry systems are gain- Afterwards the purified product was lyophilized by means of a
ing popularity due to the faster reaction kinetics and the ab- Christ freeze-dryer alpha 2–4 LSC at −85 °C and 0.37 mbar. The
sence of nondegradable kinetic chains after crosslinking in con- guluronate (G) content of the selected Alg and the degree of sub-
trast with methacrylamides.[13,16–19] In this respect, especially the stitution (DS) were determined using 1 H-NMR spectroscopy as
use of norbornene functionalities has gained importance (result- reported earlier (see Figure S1 in the Supporting Information).[11]
ing in gelatine derivative containing norbornene functionalities, The G content corresponded to 42.8%, while the DS, as a function
GelNB) as thiol-norbornene is only susceptible to light-based of the present hydroxyl groups, was determined to be 31.5%.[21]
crosslinking in contrast with other “ene” functionalities which In order to obtain hydrogel films, 5% wt/v solutions of AlgMA
can also undergo competitive thiol-Michael addition reactions in were prepared containing 2 mol (%) Irgacure 2959 in double dis-
the absence of light.[13] In commercial wound dressings, Gel is tilled water and poured between two glass plates separated with a
typically not used as only component.[20] It is usually combined silicone spacer (1 mm thick) and subsequently crosslinked using
with pectin and sodium carboxymethylcellulose in hydrocolloid UV-A irradiation for 1.5 h.
wound dressings such as Granuflex or in absorbable sponges for
hemostatic use, such as Surgifoam.
Based on the considerations presented above, modified forms 2.1.2. Development of GelNB films
of Alg and Gel, developed by our research group,[11,12] were used
as starting materials in the current work to create novel wound GelNB derivative was developed following a previously reported
dressings. The aim of this work was to develop new AlgMA and protocol.[22] In brief, the carboxylic acid functionalities in 5-
GelNB hydrogels and to investigate their moisturizing properties norbornene-2-carboxylic acid were converted into activated suc-
and wound healing effects in an in vivo acute wound model, in cinimidyl esters via reaction with EDC and NHS during 25 h, us-
order to evaluate their potential benefits over commercially avail- ing a 1.5 molar excess of 5-norbornene-2-carboxylic acid (relative
able wound dressings. to the amount of EDC added) (Figure 1).
To this end, EDC and NHS were dissolved in a respective 1:1.5
2. Experimental Section ratio in dry DMSO under argon atmosphere. Afterward, the tem-
perature was raised to 50 °C and Gel type B (10 g) was added
2.1. Materials to the reaction mixture resulting in a 2.89 mmol norbornene
succinimidyl ester relative to the primary amines present in Gel
Sodium alginate (NaAlg), methacrylic anhydride, 5-norbornene- (0.385 mmol g−1 ) and allowed to react for another 20 h.
2-carboxylic acid (predominantly endo), D,L-dithiothreitol (DTT), Next, the mixture was precipitated in a tenfold excess of ace-
deuterium oxide and sodium hydroxide (NaOH) were pur- tone, filtered on filter paper (VWR, pore size 12–15 μm) using
chased from Sigma-Aldrich. Spectra POR-4 dialysis mem- a Büchner filter to remove the formed urea side product and
branes with molar mass cut-off of 12–14 kDa were obtained DMSO, followed by dissolving in double distilled water and dialy-
from Polylab. 1-Ethyl-3-(3-dimethylamino)propyl)-carbodiimide sis for 24 h against distilled water (molar mass cut-off 12–14 kDa).
hydrochloride (EDC) was obtained from TCI Europe (Zwijn- After dialysis, the reaction mixture appeared turbid as a result of
drecht, Belgium). Dimethyl sulfoxide (DMSO) (99.85%) and the modification of the primary amines resulting in a pH close to
N-hydroxysuccinimide (98%) (NHS) were purchased from the isoelectric point of Gel (i.e., 5). Therefore, the pH of the mix-
Acros (Geel, Belgium). Irgacure 2959 (1-(4-(2-hydroxy)-phenyl)- ture was adjusted to ≈7.4 using 5 m NaOH resulting in a clearing
2-hydroxy-2-methyl-1-propane-1-one) was obtained from BASF of the solution. Finally, the pure product was isolated by freezing

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Figure 1. Synthesis of GelNB derivative.

and subsequent lyophilization. The DS was assessed using 1 H-

NMR spectroscopy using D2 O as solvent at 40 °C (Bruker WH
500 MHz) (see Figure S2 in the Supporting Information).The ap-
plied DS was 53%.[22]
To obtain hydrogel films, 10% wt/v solutions of GelNB were
prepared at 40 °C in the dark in the presence of 2 mol (%) Irgacure
2959 (relative to the number of norbornene functionalities) and
50 mol (%) DTT (relative to the number of norbornene function- Figure 2. Click-dressing applied on top of the wounds.
alities) to result in an equimolar thiol/ene ration, in double dis-
tilled water. Next, the solution was placed into two glass plates
separated with a silicone spacer (1 mm thick) and subsequently Medicine and Pharmacy from Iasi (14.07.2020) and was run ac-
crosslinked using UV-A irradiation for 0.5 h. cording to the deontology and ethics guidelines concerning lab-
oratory animal studies (Law no. 206/27 May 2004, EU/2010/63
– CE86/609/EEC). The study took place at Advanced Research
2.2. Gel Fraction and Swelling Capacity Experiments and Development Center for Experimental Medicine (CEMEX)
(certificate no. 2/22.09.2017) of “Grigore T. Popa” University of
Freeze-dried samples were weighed (m0 ) and placed in double Medicine and Pharmacy from Iasi.
distilled water, allowing them to swell for 24 h at 37 °C. The
swollen weight was then recorded (ms ) after which the samples
were freeze-dried again (mfd ). The experiments were performed 2.4.2. Wound Model
in triplicate at 37 °C.
Gel fraction (G) and swelling capacity (S) were measured, us- The rats were randomly divided into four groups, four animals
ing the following formulas[21] each group. They were anesthetized with isoflurane inhalation (2
L min−1 ) and intraperitoneally injected with tramadol solution to
G [%] = mfd ∕m0 x 100% (1) attain analgesia. Their dorsal surface skin was shaved, and two
[ ] ( ) areas (25 mm2 ) were excised, according to an established exci-
S gwater ∕gmaterial = ms − mfd ∕mfd (2) sion protocol (5 cm below the scapula and 1 cm from the clos-
est vertebral body). The tested materials were first immersed in
phosphate buffered saline (PBS) for 60 min and then the samples
2.3. Sterilization
were applied on the wound:
Sterilization was performed at the University Hospital Leuven by • Group 1 (AlgMA) – was treated with AlgMA films;
a cold ethylene oxide cycle (35 °C) for 7 h. Afterward, they were • Group 2 (GelNB) – was treated with GelNB films;
placed in a ventilation cabinet for 36 h. • Group 3 (AquacelAg) – was treated with commercial dressing
AquacelAg, and served as positive control;
• Group 4 (Help) – was treated with sterilized cotton gauze, and
2.4. In Vivo Wound Healing Assay
served as negative control;
A surgical wound model was applied to evaluate the healing ef-
fects of AlgMA and GelNB films for which the monitored param- Finally, a ʺclickʺ dressing made of a sterile gauze and a clamp-
eters included the wound contraction area and the epithelializa- ing device[23] was applied on top to secure the samples (Figure 2).
tion.

2.4.3. Wound Contraction Assessment and Macroscopic Evaluation

2.4.1. Animals
Every 3 days, the damaged tissue, fibrin, dead cells, and excess
The in vivo experiment was carried out using white adult Wis- of exudates were cleared away and the tested material samples
tar male rats (6–8 weeks old, 350–400 g). First, the animals were renewed. The renewal timeline was based on the following
were housed for 7 days, in separate polypropylene cages and time points: on the 3rd, 6th, 9th, and 12th day. At these predeter-
at constant temperature (23 ± 2 °C), relative humidity (37– mined time points, the wound surface was macroscopically an-
60%), dark/light cycles (12 h) and were fed with standard pel- alyzed and photographed. At the end of the experiment (on the
let and water ad libitum. This study was authorized by the Re- 12th day), the rats were euthanized via intracardiac administra-
search Ethics Committee of “Grigore T. Popa” University of tion of KCl (1–2 cc) under isoflurane anesthesia.

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Table 1. The healing effects of the tested materials (AlgMA, GelNB) in ref-
erence to the control groups, expressed as wound contraction (%).

Wound contraction [WC, %]

a)
Day AlgMA GelNB AquacelAg Help

Day 3 7 ± 0.8 7± 1# 6±1 7 ± 0.8

Day 6 19 ± 0.6# 23 ± 0.1* 22 ± 1* 18 ± 1.7
Day 9 36 ± 0.9# 44 ± 0.3*# 38 ± 0.4 38 ± 1.7
Figure 3. The gel fraction (G, %) and swelling capacity (S) values of the Day 12 56 ± 0.7# 80 ± 0.3*# 59 ± 0.2* 56 ± 0.8
tested materials (AlgMA, GelNB).
a)
The values are expressed as mean ± SD (n = 8 wounds), where * indicates
p < 0.05 when compared to Help cotton gauze (negative control) and # indicates
In order to assess the healing rate, wound contraction (WC, %) p < 0.05 when compared to AquacelAg (positive control).
was calculated, according to the following formula[24]

W0 − Wt characteristic for polysaccharides, which can result in the scav-

WC (%) = x100 (3) enging of free radicals.[26,27]
W0
The water uptake capacity of a dressing is an important pa-
where: W0 = wound size at day 0 and Wt = wound size at a spe- rameter in wound healing context as it provides an indication
cific time point (day 3, 6, 9, or 12). of the potential to absorb exudate from the wound. Compared
to AquacelAg (17.5 ± 1.3), especially AlgMA (32.6 ± 0.7) has a
significantly (p < 0.05) stronger swelling capacity. This is related
2.4.4. Histopathology Assay to the presence of the carboxylate and alcohol – groups caus-
ing the AlgMA to become more hydrophilic than the sodium
For the microscopic evaluation, a biopsy was harvested on the carboxymethylcellulose of AquacelAg.[28] The significantly lower
6th and 12th day from the whole wound thickness with a supple- swelling capacity of the GelNB (7.8 ± 0.2) films could be ex-
mentary 0.5 cm of healthy tissue surrounding the wound edge. A plained on the one hand by the fact that Gel is less hydrophilic
haematoxylin and eosin (H&E) staining was performed, and the than Alg. On the other hand, the films were prepared at a higher
analysis was executed using a Leica DM3000 microscope, while polymer concentration (i.e., 10% wt/v GelNB vs 5% wt/v Al-
the pictures were analyzed with Leica Application Suite (LAS) gMA), thereby already resulting in a more densely crosslinked
software which permits the visualization of the image, the pos- structure.[29] Previous research has also shown that the swelling
sibility of archiving the images obtained, a 2D measurement of capacity of Alg based hydrogels is significantly higher compared
either individual or global morphological features (such as size to Gel based hydrogels.[30]
and area of parameters defined for the entire Field of View), data Previous research has indicated that both AlgMA and GelNB
collection and correlation. are biocompatible over 7 days[18,21,31] and they remained stable
with no significant biodegradation over 3 weeks, greatly outper-
forming the required 3 days after which the dressings are typi-
2.4.5. Statistical Analysis cally changed.

The results are expressed as mean ± standard deviation (SD) and

the software package StatView was used. Data were analyzed us- 3.2. Wound Contraction Assessment and Macroscopic Evaluation
ing Analysis of Variance (ANOVA). A p value less than 0.05 is
considered statistically significant in the analysis. The wounds were evaluated throughout the 12 days of the ex-
periment and the healing effects of the materials tested (AlgMA,
GelNB) and the controls (AquacelAg and Help) were determined.
3. Results and Discussion WC (%) was determined for each group and the results are pre-
sented in Table 1.
3.1. Gel Fraction and Swelling Capacity Experiments The healing rate was consistent during the experiment. GelNB
films displayed a significant improvement of the healing process,
The gel fraction of a hydrogel provides an indication of the cross- when compared to the negative control- Help and the AlgMA
linking efficiency of a polymer network.[25] It enables to deter- films. More specifically, it displayed a WC (%) on day 12 of 80 ±
mine the amount of hydrogel chemically incorporated within the 0.3% compared to the negative control (56 ± 0.7%). This trend
polymer network, compared to the sol fraction, which is the part was continuous over the course of the experiment.
that is redissolving after incubation in an aqueous solution. It was The macroscopic assay indicated that the healing process took
found that both AlgMA (98.5 ± 0.6%) and GelNB (88.4 ± 4.4%) place without any possible complications, and no indication of
films exhibited a gel fraction exceeding 85%, with AlgMA films necrosis was observed (Figure 4).
having a significantly (p < 0.05) higher value close to 100%, in At the end of the investigation, the wounds presented more
line with literature[21] (Figure 3). As both values are above 85%, than 50% wound contraction in case of the two tested materials
this indicates a successful cross-linking. The long curing time re- groups, which suggest an accelerated healing rate, when com-
quired for AlgMA (i.e., 1.5 h) is related to the antioxidant activity pared to the negative control group. Of the two tested materials,

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Figure 4. Macroscopic evaluation of wound area of the tested materials (AlgMA, GelNB) in reference to the controls (AquacelAg, Help) at various
timelines.

only GelNB films presented significant improvement when com- adipose tissue was absent and replaced by mature granulation tis-
pared to the positive control group treated with AquacelAg. Still, sue. On the 12th day, the epidermis was denuded and covered by
AlgMA proved its efficacy, with similar results to the negative leukocytic exudate, yet with regenerated epidermis at the periph-
control group (wound contraction started from 7 ± 0.8% when ery. In the superficial dermis, granulation tissue was present in
checked on day 3 and up to 57 ± 0.8% on day 12). To further in- proliferative phase (as fibro-vascular granulation tissue) and ves-
tegrate these results, a histopathology assay was conducted. sels were also present, with vertical orientation, while in the deep
dermis, the granulation tissue was in the maturation phase (ma-
ture granulation tissue, fibrosis with numerous myofibroblasts)
3.3. Histopathology Assay and there was a sudden transition from the regenerated dermis
to the normal dermis.
As both Alg and Gel are natural polymers frequently used for The group treated with AlgMA films presented similar char-
wound healing applications,[30,32,33] films constituted of a Gel ver- acteristics as the GelNB group in the epidermis layer, yet in
sus an Alg derivative were evaluated for their in vivo wound heal- the dermis, oedema was present as well as acute inflammatory
ing potential, while benefits and limitations were highlighted for infiltrate organized in a thin band, with hair adnexa still absent.
both material classes. This may have caused the slightly slower healing rate compared
On the 6th day, the group treated with GelNB films presented to the GelNB group. On the 6th day, there was a large area of
a large area of denuded epidermis (Figure 5), covered by leuko- denuded epidermis, with regenerative aspects at the borders:
cytic exudate (without underlying fibrinoid necrosis), granulation thick epidermis with balonised cells in the basal layer, spon-
tissue in proliferative phase (fibro-vascular granulation tissue) giosis, acanthosis in the spinous layer and para-keratinization.
in the superficial dermis and granulation tissue in maturation In continuity with thin epidermis (cubic cells in basal layer,
phase (mature granulation tissue, with reactive fibroblasts), with minor aspects of spongiosis and acanthosis in spinous layer),
extension into the muscular cells adjacent to the lesion in the keratohyalin granules indicated the granulous layer with thin
deep dermis layer. Hair adnexa were absent. In the hypodermis, lamellar keratin being present. Fibrous connective tissue, with

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Figure 5. Microscopic evaluation of wound areas treated with the hydrogel films (AlgMA, GelNB) in reference to the controls (AquacelAg, Help cotton
gauze).

regenerated hair follicles (buds) was observed in the superficial sis on the 6th day toward a denuded epidermis, partially covered
and deep dermis. On the 12th day, the healing process evolved by fibrino-leukocytic exudate with regenerated epidermis at the
toward the appearance of fibrous connective tissue, yet with a periphery and mature granulation tissue in the dermis layer on
poorly represented inflammatory infiltrate in the dermis layer. the 12th day.
In the case of the AquacelAg group the healing process evolved Previous studies suggest that an Alg-based matrix may pro-
from an atrophic epidermis alternating with denuded epidermis mote wound healing by keeping a moist microenvironment at
and hemato-fibrino-leukocytic exudate on the 6th day toward a the wound site, while calcium ions present in such commercial
regenerated epidermis with granulation tissue in proliferative dressings or at the wound site can be helpful in early stages
phase which is evolving toward maturation phase on the 12th day. of wound healing as they are important in regulating clotting
The Help negative control group evolved from a denuded epider- mechanisms.[34] A Gel-based matrix may promote epithelializa-
mis and thick leukocytic exudate with underlying fibrinoid necro- tion and the formation of granulation tissue, while it presents a

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high biocompatibility, strong biodegradability, and low antigenic- Keywords

ity as it is produced by the hydrolysis of its precursor compound,
collagen. alginate, gelatin, hydrogels, wound healing
Based on the present findings and previous studies, especially
Received: June 6, 2021
GelNB films are promising toward the wound healing market as
Revised: July 31, 2021
it is even outperforming the commercially available AquacelAg. Published online:

4. Conclusions
In this study, AlgMA and GelNB films were developed and char- [1] K.-P. Wilhelm, D. Wilhelm, S. Bielfeldt, Ski. Res. Technol. 2017, 23, 3.
acterized through gel fraction and swelling capacity experiments. [2] C. K. Sen, Adv. Wound Care 2019, 8, 39.
This has shown by a successful crosslinking as reflected by the [3] J. F. Guest, N. Ayoub, T. Mcilwraith, I. Uchegbu, A. Gerrish, D. Wei-
gel fractions exceeding 85%, while both materials showed a high dlich, K. Vowden, P. Vowden, Int. Wound J. 2017, 14, 322.
swelling capacity, in particular AlgMA. Subsequently, the films [4] J. Koehler, F. P. Brandl, A. M. Goepferich, Eur. Polym. J. 2018, 100,
were tested in vivo on a Wistar rat wound model for their healing https://doi.org/10.1016/j.eurpolymj.2017.12.046
effects. The GelNB films were found to promote wound healing [5] S. Hasatsri, A. Pitiratanaworanat, S. Swangwit, C. Boochakul, C. Tra-
activity (a wound contraction of 80 ± 0.3% on the 12th day of goonsupachai, Dermatol. Res. Pract. 2018, 2018, 9367034.
[6] V. Vachhrajani, P. Khakhkhar, in Science of Wound Healing and Dressing
the experiment) to a greater extent compared to the AlgMA films
Materals, Springer, Singapore 2020, p. 59.
(56 ± 0.7%), AquacelAg (used as positive control) and Help cot-
[7] K. Y. Lee, D. J. Mooney, Prog. Polym. Sci. 2012, 37, 106.
ton gauze (used as negative control). The AlgMA films performed [8] G. Klöck, A. Pfeffermann, C. Ryser, P. Gröhn, B. Kuttler, H.-J. Hahn,
significantly less than AquacelAg yet similar to Help. Further- U. Zimmermann, Biomaterials 1997, 18, 707.
more, H&E staining results suggest that the GelNB films pro- [9] G. D. Mogoşanu, A. M. Grumezescu, Int. J. Pharm. 2014, 463, 127.
moted transition to normal dermis, which is indicative for an [10] H. M. C. Azeredo, K. W. Waldron, Trends Food Sci. Technol. 2016, 52,
improved wound healing process. The hypothesis of this study 109.
was that the wound dressings based on AlgMA and GelNB would [11] A. Mignon, J. Vermeulen, G.-J. Graulus, J. Martins, P. Dubruel, N. De
benefit the wound healing process when compared to the nega- Belie, S. Van Vlierberghe, Carbohydr. Polym. 2017, 168, 44.
tive control (Help cotton gauze) and positive control AquacelAg, [12] G.-J. Graulus, A. Mignon, S. Van Vlierberghe, H. Declercq, K. Fehér,
M. Cornelissen, J. C. Martins, P. Dubruel, Eur. Polym. J. 2015, 72,
due to the hydrogel maintaining a moist environment and the
494.
results confirm it.
[13] J. Van Hoorick, L. Tytgat, A. Dobos, H. Ottevaere, J. Van Erps, H.
Moreover, these results indicate the potential of films consti- Thienpont, A. Ovsianikov, P. Dubruel, S. Van Vlierberghe, Acta Bio-
tuting GelNB versus AlgMA as effective treatment alternatives mater. 2019, 97, 46.
to support wound healing. Also in future research, the wound [14] A. I. Van Den Bulcke, B. Bogdanov, N. De Rooze, E. H. Schacht, M.
healing potential of AlgMA films could possibly be improved by Cornelissen, H. Berghmans, Biomacromolecules 2000, 1, 31.
for example introducing cell-interactive properties with Laponite [15] J. Van Hoorick, P. Gruber, M. Markovic, M. Tromayer, J. Van Erps, H.
nanoparticles. Thienpont, R. Liska, A. Ovsianikov, P. Dubruel, S. Van Vlierberghe,
Biomacromolecules 2017, 18, 3260.
[16] J. Van Hoorick, A. Dobos, M. Markovic, T. Gheysens, L. Van Damme,
Supporting Information P. Gruber, L. Tytgat, J. Van Erps, H. Thienpont, P. Dubruel, A.
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