Chemical Papers (2024) 78:1021–1031

https://doi.org/10.1007/s11696-023-03140-4

ORIGINAL PAPER

Dual‑adhesive and self‑healing alginate‑based hydrogel for wound

healing
Naglaa Salem El‑Sayed1 · Naiera M. Helmy2 · Samir Kamel1

Received: 25 July 2023 / Accepted: 6 October 2023 / Published online: 25 October 2023
© The Author(s) 2023

Abstract
Some of the wound dressings on the market cause skin tearing and bleeding when removed, slowing the healing process.
So, it is difficult to treat infected wounds of sensitive skin patients. Herein, antibacterial and biocompatibility self-healing
hydrogel loaded with 9-Aminoacridine and kanamycin sulfate were prepared by grafting poly(β-carboxyethyl acrylate-co-
acrylamide) onto sodium alginate. The biological assay demonstrated the hydrogels’ good biocompatibility, which showed
no harmful effects on normal human melanocyte cells. In addition, the hydrogels had a powerful antibacterial impact on the
various bacterial strains utilized in the investigation. From the study of the rheological properties of the prepared hydrogel,
it was found that it is a non-Newtonian fluid. These results suggest the possible utilization of the as-prepared hydrogels in
the fabrication of wound healing.

Keywords Sodium Alginate · Self-Healing · 9-Aminoacridine · Kanamycin · Interpenetrating and Antimicrobial Hydrogel

Introduction hydrogel-based-alginate can keep the surrounding region

wet, absorb wound exudate, and aid healing. Divalent cat-
Hydrogels are the most significant candidate for wound ion crosslinking (Lazow et al. 2021), Amidation reaction
dressing compared to other materials due to their high (Froelich et al. 2023), and carboxyl-based chemical modi-
water content, elasticity, biocompatibility, adequate flex- fication (Du et al. 2020) are the main preparation methods
ibility, and physiological sensitivity (Kamoun et al. 2017; of this hydrogel. Additionally, in vivo, alginate cannot be
Sood et al. 2014). Recently efforts have been dedicated to biodegraded, so oxidized alginate is utilized to prepare adhe-
developing hydrogels with multi-functional properties, such sive hydrogel (Cao et al. 2019). Except for divalent cation
as adhesive, high mechanical and self-healing. On the other crosslinking, amidation reaction, and dopamine-modified
hand, due to their distinctive biological activity (such as the alginate as the same as oxidized alginate can react with
hemostatic and antibacterial properties), low immunologi- a variety of amino-containing crosslinking agents (such
cal response, good biocompatibility, simplicity of physical as protein and amino-containing polysaccharides, etc.) to
and chemical modification, the abundance of supplies, and produce adhesives hydrogel by Schiff base reaction (Chen
inexpensive cost, polysaccharides are frequently utilized for et al. 2018). Wound adhesives hydrogel has varied adhe-
hemostasis and wound healing (Li et al. 2022b). Alginate sion strategies to deal with the various tissue surface and
is one of these polysaccharides, a structure similar to the environments of different types of wounds. The adhesion
native extracellular matrix, and is commonly used to make mechanisms can be chemical, physical, or bionic adhesion.
hydrogel wound dressing (Kamel et al. 2023). Adhesives Chemical adhesion relates to the covalent crosslinking
between carboxyl, amino, and thiol (amino acid residues
in proteins) of tissue and hydrogel active groups such as,
* Samir Kamel
[email protected] N-hydroxysuccinimide esters (Zhang et al. 2021), aldehyde
(Qu et al. 2018), polyphenols (Zhao et al. 2020), and aryl
1
Cellulose and Paper Department, National Research Centre, azides (Ono et al. 2000) of hydrogel. Physical adhesion
P.O. 12622, Giza, Egypt mainly includes hydrogen bond interactions (Zhang et al.
2
Microbial Biotechnology Department, Biotechnology 2020), van der Waals forces (Autumn et al. 2002), electro-
Research Institute, National Research Centre, P.O. 12622, static interactions, p–p or cation–p interaction forces (Zhao
Giza, Egypt

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1022 Chemical Papers (2024) 78:1021–1031

et al. 2020), electrostatic interactions (Wang et al. 2020), was purchased from Bio Basic Inc., Canada. Acridine orange
and hydrophobic interaction (Nishiguchi et al. 2020). While purchased from (oxford Lab Chem.). Normal human skin
bionic adhesion includes mussel adhesion, gecko adhesion, cell line (HFB-4) was purchased from VACSERA, Egypt.
etc. (Li et al. 2022a). All chemicals used throughout the work were of the highest
In addition to the adhesive property, self-healing is more analytical grade.
attractive due to their healing ability after damage like tissue
(Chen et al. 2018). The mechanisms of hydrogel self-heal- Preparation of hydrogel
ing include non-covalent and covalent bonds such as Schiff
bases, hydrogen bonds, coordination bonds, and Diels–Alder Hydrogels were prepared according to the method described
reactions (Khattab and Kamel 2022). Also, the cross-linked in reference (El-Sayed et al. 2023). In brief, to 25 mL of 4%
hydrogels by dynamic bonds lead to self-healing capaci- alginate solution, 0.060 g KPS was added after removing
ties. As the destruction of hydrogel, the internal dynamic dissolved oxygen by purging the nitrogen gas into the algi-
cross-linked networks reverse the fracture and reorganize nate solution for 10 min. Then, an aqueous miture of 2 g AM
the hydrogels. Wu et al. prepared a fast self-healing hydrogel and 1 g CEA was neutralized by KOH solution and mixed
by mixing polyvinyl alcohol and 3-aminophenylboronic acid with the above alginate solution; the pH of the mixture was
grafted alginate. To increase its cold resistance and electrical adjusted to 5.5. After 1 h, an aqueous MBA (0.124 g) was
conductivity, glycerin and inorganic salts were added to the added to the reaction mixture, raised the temperature to 70,
hydrogel (Wu et al. 2020). Lu et al. developed self-healing and continued stirring for 2 h additional. The formed hydro-
hydrogel based on dialdehyde alginate/ polyethyleneimine gel was washed with water, and the unreacted monomers,
and loaded strontium-ion. The prepared hydrogel could homopolymer, and alginate were removed by immersing
self-heal breaks in the gel and tightly adhere to the wound, the hydrogel in boiling acetone. The hydrogel was collected
solving the problems of skin defect repair and sports reha- and freeze-dried. For drug loading, 9-AA and KS sulfate
bilitation. In addition, the slow release of strontium ions aqueous solution were added individually onto the hydrogel
from hydrogel quickly heals the wound by promoting angio- mixture after adding MBA for 10 min.
genesis and collagen deposition (Lu et al. 2020). For drug loading, an aqueous solution of 9-Aminoacri-
In this study, a mechanically tough self-healing conduct- dine hydrochloric salt (25, 50, and 100 mg/5mL H ­ 2O) or
ing adhesive hydrogel was prepared for potential wound kanamycin sulfate (50 mg/5mL H ­ 2O) was added individually
dressing applications. The hydrogels were designed based onto the hydrogel mixture after adding MBA for 10 min. The
on sodium alginate grafted poly(β-carboxyethyl acrylate-co- as-prepared hydrogels have the following code names: (S1)
acrylamide), potassium persulfate was employed as initia- the hydrogel without drugs, (S2, S3, and S4) the hydrogel
tor, N, N-dimethylbisacrylamide was used as crosslinker. loaded with 9-AA at 25, 50, and 100 mg/1g of SA, (55) the
In addition, 9-Aminoacridine and kanamycin sulfate were hydrogel encapsulating KS (50 mg/gSA).
separately added to the hydrogel mixture following the addi-
tion of the crosslinker. The hydrogel formation proceeded Characterization
via the formation of free radicals on the alginate surface by
the persulfate free radicals. The alginate free radicals attack The FT-IR spectra for SA, S1, S3, and S5 were measured by
the vinyl double bonds of the monomers, leading to chain FT-IR (Nicolet Impact-400 FT-IR spectrophotometer) in the
propagation and crosslinked with dimethylbisacrylamide. range of 400–4000 ­cm−1.

Self‑healing ability of the hydrogel

Materials and methods
The ability of the hydrogel to repair after cutting was deter-
Material mined by longitudinal cutting of one piece of the hydrogel
into two pieces. The two pieces were kept in proximity and
Sodium alginate (SA), β-carboxyethyl acrylate (CEA), and assembling of the pieces into one piece was achieved with
kanamycin sulfate (KS) were purchased from Sigma Aldrich, in together, they were able to retain their original shape and
9-Aminoacrydine (9-AA) was purchased from Merck. gather into one piece within 60–90 s.
Acrylamide (AM) was from Fluka, and N,N-methylenebi-
sacrylamide (MBA) and potassium persulfate (KPS) were Adhesion test
purchased from Across. RPMI-1640 medium, fetal bovine
serum (FBS), and trypsin–EDTA was purchased from To measure the adhesive strength of hydrogel, Stainless-
GIBCO™, Grand Island, New York, USA, 3-(4,5-dimeth- steel, glass, rubber, and plastic were applied for the adhere
ylthiazol-2-yl)-2,5-diphenyl)- tetrazolium bromide (MTT) test.

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Chemical Papers (2024) 78:1021–1031 1023

Rheological measurement about 90% confluent when treated with compounds and incu-
bated for 24 h at 37 °C. After treatment, the Hydrogels were
Rheological measurements of the hydrogel were carried discarded then cells monolayers were washed with PBS. The
out through a rotational rheometer, MCR 301 Rheometers, cells were fixed with 10% paraforamaldehyde and stained
Anton Paar, GMbH, Germany. All rheology measurements with 60 µg/ml acridine orange. The cells were examined
were made using a 1 mm diameter, and the temperature was with ZOE Fluorescent Cell Imager fluorescence microscopy
controlled at 25 °C. Before testing, samples were left equili- (BIO-RAD,USA) (Thomé et al. 2016).
brating for five minutes to allow mechanical equilibrium.
Flow curves were made in control rate mode (CR), varying In vitro wound healing assay
the shear rate (0.1–10 rad/s) at 20 °C.
Normal Human skin cells (3 X 105 cells/well) were cultured
Electric conductivity measurement in 24 well plates and incubated in a humidified cell incuba-
tor containing 5% C ­ O2 and 95% air at 37 °C with RPMI
Electrical measurements were performed using stainless supplemented with 1% penicillin–streptomycin, 1% non-
steel electrodes and the powerful alpha analyzer described essential amino acids and 10% fetal bovine serum (FBS).
in our previous work. The measuring cell comprises two After incubation, the cell's monolayers were washed twice
parallel stainless-steel electrodes separated by a Teflon cir- with PBS. A vertical scratch was applied using 10–100 μL
cular ring of 2mm thickness and 20mm diameter (El-Sayed pipette tip across each well. The washing process through
et al. 2019). PBS helped to remove the detached cells; this was followed
by adding low serum fresh medium to each well, and then
Cytocompatibility assay the image for the scratch was token at zero time. The hydro-
gel samples S50A and S50K (20 mg), and a mixture from
MTT assay both hydrogels (20 mg each one) were used after steriliza-
tion for 30 min under UV. The scratch closure was imaged
Normal human skin cell line (HFB-4) were purchased from after 6 h using ZOE Fluorescent Cell Imager fluorescence
VACSERA, Egypt. Cells were allowed to grow in a humidi- microscopy (BIO-RAD, USA). The analysis of the scratch
fied cell incubator containing 5% ­CO2 and 95% air at 37 °C width is calculated using the Image J public domain software
with RPMI supplemented with 1% penicillin–streptomycin, (Kamel et al. 2023).
1% non-essential amino acids and 10% fetal bovine serum
(FBS). The cells were grown in 96 well plates to ~ 70% con-
fluence and the cells then were treated with along with the Results and discussion
DMSO control and incubated for about 24 h. The media
were removed and replaced with 120 µL and 30 µL of MTT Earlier, we described the preparation and characterization of
3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bro- new hydrogel based on sodium alginate. The hydrogel was
mide solution at 5 mg/ml was added to each well then plates prepared by graft polymerization on the surface of SA with
were incubated with for 4 h at 37 °C in a humidified C ­ O2 poly(β-carboxyethyl acrylate-co-acrylamide). Then, 9-AA
incubator. After removal of each well supernatant, addition was encapsulated into it. Similarly, KS (a broad-spectrum
of 100 µL Dimethylsulphoxide (DMSO) was into each well antibiotic) was also physically incorporated into the hydro-
for color development and then the plates were incubated gel loaded at 5% wt/wt. FT-IR confirmed the structure for
for 10 min under shaking conditions. Finally, the absorbance the as-prepared hydrogels. Also, the thermal stability and
was measured at 490 nm with a microplate reader (Nelson morphological features were determined by TGA and SEM
et al. 2020). in our previous report. Moreover, the hydrogel swelling
study, pH-responsive drug release, antimicrobial activity,
Cytocompatibility using acridine orange staining and cytocompatibility towards normal lung cell line (VERO)
cells were reported (El-Sayed et al. 2023) Fig. 1.
Normal human skin cell line (HFB-4) were purchased from
VACSERA, Egypt. Different concentrations of Hydrogels Characterization of hydrogels by FT‑IR
were prepared from each group (0.01, 0.02 and 0.03 gm).
The concentrations are used for treating previously cultured The grafting of SA and drug loading was characterized by
cells in 48 well plate in a humidified cell incubator contain- FT-IR spectra (Fig. 2). SA spectrum displayed characteristic
ing 5% C ­ O2 and 95% air at 37 °C with RPMI supplemented absorption bands at 3422 and 3223, 2923, 1608, 1415, 1393,
with 1% penicillin–streptomycin, 1% non-essential amino and 1123 ­cm−1. These peaks are assigned to the inter- and
acids and 10% fetal bovine serum (FBS). The cells reached intra-molecular hydrogen bonds, stretching bands for the

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1024 Chemical Papers (2024) 78:1021–1031

SA
9-AA
P(AM)
P(CEA)
KS
MBA

Fig. 1  Schematic representation for the hydrogels structures (adapted from (El-Sayed et al. 2023))

different −OH groups, aliphatic C–H, asymmetric vibra- N–H bonds. The slight red shift of the stretching vibration
tions of carboxylic and carbonyl groups, stretching (–C–O), peaks from 3422 for SA to 3405 ­cm−1 confirms that hydro-
and the bending band for –OH groups over the SA chains gen bonding is the main interaction between 9-AA and the
(El-Sayed et al. 2022a). The appearance of strong absorp- hydrogel network (Jafarigol et al. 2020). In comparison, the
tion bands at 1719, 1656, and 1458 ­cm−1 in the IR spec- stretching bands for the aliphatic and aromatic C–H bonds
trum of S1 hydrogel, which are correlated to the overlapped were recognized in the region between 2931–2846 ­cm−1.
ester, carboxylic, and amidic carbonyl groups of BMA, The characteristic sharp and moderate intensity peaks at
poly(ECA), poly(AM), and bending NH respectively proofed 1731, 1662, and 1604 ­cm−1 are assigned to the stretching
the success of graft polymerization. Meanwhile, the two dis- carboxylate anion and ­CONH2 groups (Zheng et al. 2023).
tinctive bands observed at 1485,1406 and 1028 ­cm−1 repre- The stretching C–O and C–N bonds displayed 1550 and
sent the bending C–O, C–N, and the deformation vibrations 1454 ­cm−1 peaks. Also, the sulphonic groups' symmetric
of C–O–C or C–O–H groups. The spectrum of S3 revealed and asymmetric S–O stretching vibration can be observed
the peaks at 3405 and 3186 ­cm−1 are due to the OH and at 1388 ­cm−1 for (υas S
­ O2) and 1172 ­cm−1 for (υsym ­SO2),
­NH2 groups, intermolecular H-bonds, and the stretching respectively. The stretching absorption band at 1110 ­cm−1

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Chemical Papers (2024) 78:1021–1031 1025

Fig. 2  FTIR-spectra of SA, S1,

S50K, and S25A, (adapted from
(El-Sayed et al. 2023))
S3

2836

1731
2926
3434 1602
1662
3175
S5

1388
2849 1733 1462
2919 1608
T ( %) 3442 3215 1654

S1

1719

1027

1611 1431 1119

3218
SA 3434

2850 1106
1393
2923
1608 1415
3422
4000 3500 3000 2500 2000 1500 1000

wavenumber[cm-1]

is for the stretching –C–O bond. For the S5 spectrum, a hydrogels were dyed individually with methylene blue and
similar assignment is applied for the peaks at 3409, 3215, methyl red into blue and red and molded in a rectangular-
2919–2849, 1733, 1654, 1608, 1575, 1462, 1388, 1171, and shaped mold. After cutting the hydrogel, the hydrogel was
1049 ­cm−1, respectively (El-Sayed et al. 2022c). simulated as destroyed, and the healing status was observed
as the two hydrogels healed together. However, by bring-
Self‑healing ability of the hydrogel ing the two halves into contact, hydrogen bonds between
hydroxyl and amino groups in the hydrogel and amide bond
Traditional hydrogel dressings cannot self-heal, and exter- between grafted alginate and drug-loaded functional groups
nal mechanical forces quickly damage them. However, the reformed, recovering the hydrogel.
self-healing hydrogels may repair themselves after breaking,
extending their useful life and reducing the risk of wound Rheology studies
infections (Li et al. 2023). To study the self-healing behav-
ior of S2 and S5 hydrogels, each hydrogel disc was cut into The rheological properties of the hydrogel are essential
two halves and brought into physical contact (Fig. 3). Con- factors in determining the mechanical properties of the
sequently, the author lifted the hydrogel after healing, and hydrogels. Consequently, we have measured the viscosity
it can be seen restoring the mechanical properties of the and Torque of the hydrogel loaded with 9-AA in a range
hydrogel after self-healing. Also, as shown in Fig. 3, the of 1–100 ­s−1 of shear rate (Fig. 4). Accordingly, it showed

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1026 Chemical Papers (2024) 78:1021–1031

Fig. 3  Photographs showing the cut–heal test; the hydrogel was cut in half and the two halves were contacted and self-healed

the strong hydrogen bonding between the substrate sur-

face (plastic, metal, glass, or rubber) and the hydrogel's
different functional groups. The free hydroxyl and amino
groups dispersed in the hydrogel could react with amine
or thiol-containing substrates via Michael-type addition
reactions or aryl–aryl coupling (Lee et al. 2006). Also,
many carbonyl groups in hydrogel chains can contribute to
adhesiveness through amide bonds with the amino group.

Electrical conductivity

The typical frequency dependence at room temperature

Fig. 4  Viscosity and Torque versus shear rate on the conductivity function σ′ and iσ′′ for the prepared
hydrogel was presented in Fig. 6. From the Figure, at
100 kHz frequencies, the transportation of the charge
a shear-thinning behaviour, non-Newtonian behaviour as is the response of conductivity and dielectric functions.
viscosity decreases under shear strain, and a high drop of Also, from Figure, it is noticed that at ~ 106 Hz, the
its viscosity was observed. Concurrently, the Torque, the complex conductivity (σ″) reduced to a minimum value
material's resistance to the shearing action, was increased by followed by sharp increase of the real permittivity (ε′),
increasing the shear rate (Belalia and Djelali 2014). which is the beginning of the electrode polarization devel-
opment. At the critical frequency (νc), the conductivity
Adhesive property of hydrogels rises parallel with the decrease in real permittivity. This
phenomenon is characteristic of the complete build-up
The hydrogels were checked for their adhesion ability to of the electrochemical double layer, or what is known as
various substrates. Figure 5 shows the strong adhesive electrode polarization. Decreasing frequency showed an
ability of the hydrogels, S2 and S3, on stainless steel, upward bending-like behavior at 10 Hz in imaginary and
glass, rubber, and plastic. The adhesion ability of the real parts of the complex conductivity, which is the final
hydrogels to adhere to the substrates surfaces is due to blocking of a second charge-transport mechanism.

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Chemical Papers (2024) 78:1021–1031 1027

Fig. 5  Photographs showing

the hydrogel tightly adhered to
various substrates

2017). In this assay, the cellular mitochondrial dehydro-

genase reduction capacity of the yellow water-soluble sub-
strate 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium
bromide (MTT) taken by the living cells. The formazan of
the insoluble dark blue/purple formazan product is directly
proportional to the number of living cells. MTT assay is
used to determine the cytotoxic effect of both the hydrogel
with and without the drugs, 9-AA, and KS, the results are
shown in Fig. 7.

Cytocombitability of the hydrogels using acridine orange

staining

Further investigation for cytocompatibility was done using

acridine orange dye to determine the viability of cells after
Fig. 6  Electroconductivity of the hydrogel loaded with 9-AA treatment, and the results are shown in Fig. 8. When the
hydrogel without the drugs (10 mg/mL) was incubated
with the cells in 96 well plates, the MTT assay revealed a
Cytocompatibility study by MTT assay reduction of 70% in the viable cells, which can be attrib-
uted to the hydrogel's ability to absorb the media from the
Cytocompatibility study by MTT assay well leading to insufficient nutrient which may contribute
to increased cell death. Surprisingly, the same hydrogel at
MTT detection of capability is considered a reliable, sen- the same concentration displayed a negligible cytotoxic
sitive, and quantitative cell viability assay (Ogbole et al. effect on the cells when live/dead cells assay was applied,

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1028 Chemical Papers (2024) 78:1021–1031

Fig. 7  Cell viability of KS,

9-AA using MTT assay at dif-
ferent drug concentrations

0.01g (I) 0.02g (II) 0.03g (III) Fig. 8. Meanwhile, 9-AA exhibited a powerful cytotoxic
effect in a dose-dependent manner. It is almost toxic at
a 0.25 and 0.5 µg/mL, as shown in Fig. 8a, b. Also, this
contributes to the determined I­ C 50 of 9-AA after MTT
assay 0.3 µg/mL. Instead, KS at 0.5 µg/mL was safe and
supported cell growth and proliferation.
The staining of live cells with acridine orange revealed
b the following observations.

• Hydrogels encapsulating 9-AA with three different

loading percents 92.5, 88.6, and 86.9%, displayed mini-
mal toxicity against the HFB-4 cells even with increas-
c
ing the hydrogel mass (10, 20, and 30 mg), suggesting
efficient encapsulation of the drugs in the hydrogel and
its sustained release at pH 7.4.
• The cytocompatibility for the hydrogel loaded with
d 9-AA was comparable to the hydrogel without the
drugs, as indicated in figures a (I-III), b (I-III), c (I-III).
• Similarly, the hydrogel loaded with 89.3% KS loading
was cytocompatible at all treatments, with a notable
e increase in the cell population with increasing hydrogel
masses, Fig. 7d (I–III) (Gu et al. 2022).
• 9-AA toxic effect was detected on cells when 0.25 and
B (hydrogel 0.5 µg/mL were incubated with monolayers HFB-4
Control
without drug) cells. o the other hand, the free kanamycin at 0.5 µg/
mL concentration, was considered safe on cell mon-
olayers. The cytotoxicity of 9-AA could be explained
by the reported ability of 9-AA to inhibit the activity of
f
topoisomerase enzymes and other regulatory proteins
such as PI3K/AKT/mTOR, p53, and TNF, that regulate
K(0.5µg/ml) 9AA(0.25µg/ml) 9AA(0.5µg/ml) the proliferation and migration (Baguley et al. 2003;
El-Sayed et al. 2022b; Mangueira et al. 2022).
Fig. 8  Live/Dead staining images of HFB-4 cells after culture in the
hydrogel for 24 h at 37 °C. a S2, b S3, c S4, d S5, e S1

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Chemical Papers (2024) 78:1021–1031 1029

Gel Scratch at zero time After 6 hours of incubation in curing the scratch (Fig. 10). The scratch examination
after treatment revealed that S50K was the most potent
in accelerating the wound healing process by decreasing
the scratch gap from both sides by 26.3%. On the other
S5 hand, the ability of S50A to heal the induced scratch was
neglectable (the gap between the two scratch sides was
reduced by 2.5%). However, treating the scratch with a
mixture of hydrogels led to a notable gab-closing ability
but still less than S50K. Overall, the results reflected a
remarkable impact of S50K in inducing the scratch closing
S3 within 6 h compared to S50A.

Conclusion

In summary, a self-healing hydrogel with conductive and

MIX
adhesive properties was prepared by grafting alginate with
poly(β-carboxyethyl acrylate-co-acrylamide) to have a car-
boxylic and carbonyl bonds, which can form a dynamic
bond. In addition, 9-Aminoacridine and kanamycin sulfate
were added to improve the antibacterial and anti-infection
Fig. 9  Scratch exposure after 6 h of treatment with S50K and S50A
and the mixture of both, the scale is 100 µm activities. As a result, the prepared hydrogels displayed
electrical conductivity and adhesive with non-Newtonian
fluid and could heal after damage. In addition, the hydro-
gels had antimicrobial and cytotoxicity properties, allow-
ing them to have potential wound-healing applications.
Finally, the in vitro wound-healing assay revealed the
promising ability of the hydrogel-encapsulating kanamy-
cin to induce scratch-healing within six hours by 26.3%.
Acknowledgements The authors acknowledge the National Research
Center (NRC), Egypt, for financial support of the current work.

Author contributions NSES contributed to conceptualization, per-

formed all chemical synthesis and materials characterization, writing
and reviewing the manuscript. NMH contributed to cytocompatibility
study, wound healing assay, writing and reviewing the manuscript.
SK contributed to conceptualization, validation, and reviewing the
manuscript.

Funding Open access funding provided by The Science, Technology &

Fig. 10  The scratch measurement at zero time and after 6 h incuba- Innovation Funding Authority (STDF) in cooperation with The Egyp-
tion with the hydrogels tian Knowledge Bank (EKB).

Availability of data and materials The data sets used and/or analyzed
during the current study are available from the corresponding author
In vitro wound healing assessment on reasonable request.

The efficacy of the S50K and S50A hydrogels in mediat- Declarations

ing the normal skin cells to heal the scratch was assessed
in vitro using normal human skin fibroblast cells (HFB-4 Conflict of interest The authors declare that they have no conflict of
interest.
cells). Following the simple cell migration assay (Bek-
tas et al. 2020), a linear thin scratch (wound) in a con- Ethics approval Not applicable.
fluent cell monolayer was created (Fig. 9). Afterward,
the images of the cells merging the gap at different time Consent to participate Not applicable.
intervals showed the effectiveness of the active compounds

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1030 Chemical Papers (2024) 78:1021–1031

Consent for publication The authors approve the publication of the Gu J, Zhang S, Xia X, Zhang X, Fan B, Zhou J, Zhu H, Wang W,
manuscript. Qi X, Li L (2022) An edible kanamycin sulfate cross-linked
cellulose active against multiple pathogenic bacteria. Int J Biol
Macromol 194:435–444
Open Access This article is licensed under a Creative Commons Attri-
Jafarigol E, Salehi MB, Mortaheb HR (2020) Preparation and assess-
bution 4.0 International License, which permits use, sharing, adapta-
ment of electro-conductive poly (acrylamide-co-acrylic acid)
tion, distribution and reproduction in any medium or format, as long
carboxymethyl cellulose/reduced graphene oxide hydrogel with
as you give appropriate credit to the original author(s) and the source,
high viscoelasticity. Chem Eng Res Des 162:74–84
provide a link to the Creative Commons licence, and indicate if changes
Kamel S, Dacrory S, Hesemann P, Bettache N, Ali LM, Postel L, Akl
were made. The images or other third party material in this article are
EM, El-Sakhawy M (2023) wound dressings based on sodium
included in the article’s Creative Commons licence, unless indicated
alginate-polyvinyl alcohol–moringa oleifera extracts. Pharma-
otherwise in a credit line to the material. If material is not included in
ceutics 15:1270
the article’s Creative Commons licence and your intended use is not
Kamoun EA, Kenawy E-RS, Chen X (2017) A review on polymeric
permitted by statutory regulation or exceeds the permitted use, you will
hydrogel membranes for wound dressing applications: PVA-
need to obtain permission directly from the copyright holder. To view a
based hydrogel dressings. J Adv Res 8:217–233
copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Khattab TA, Kamel S (2022) Advances in polysaccharide-based
hydrogels: Self-healing and electrical conductivity. J Mol Liq
352:118712
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