| Chitosan |
Honey |
A honey, chitosan, poly(vinyl
alcohol), and gelatin containing hydrogel was designed by implementing
freeze–thawing method and physical cross-linking approach.
While designing the hydrogel, different concentrations of honey were
used, while the ratio of chitosan, poly(vinyl alcohol), and gelatin
was kept in the proportion of 2:1:1 (v/v), respectively. An in vivo study of the designed hydrogel demonstrated
no toxicity and similarity in microstructure of the hydrogel with
the structure of ECM. The result of the MTT assay confirmed the growth
of the cell and reduction in the area of zone of inhibition. An in
vivo study of the formulation displayed the maturation of collagen
and re-epithelialization on the 20th
day after treatment in the groups treated with the formulation as
compared to the group treated with gauze (control group). |
(34) |
| |
Metal ions (silver, zinc,
and copper) |
Metal
ions such as silver,
zinc, and copper were combined with chitosan to prepare a hydrogel
using a freeze–thaw method. The hydrogel was further coated
on the surface of ordinary gauze for the management of chronic wounds.
An in vivo study of the formulation demonstrated significant antibacterial
effect due to the release of the metal ions from ordinary gauze. The
release of metal ions was effective in killing S. aureus and also improved the keratinocytes migration. The in vivo results
displayed the formation of tissue, deposition of collagen, and maturation.
Additionally, immunochemistry and immunofluorescence staining of newly
grown tissue confirmed the angiogenesis, re-epithelization, and reduction
in inflammation. |
(35) |
| |
Silver nanoparticles |
A silver nanoparticles impregnated
chitosan–PEG hydrogel was formulated by using glutaraldehyde
as a cross-linking agent for the management of wound in a type-2 diabetic
rabbit model. The optimized formulation displayed significant antioxidant
and antibacterial effects in in vitro analysis. An in vivo experiment
in type-2 diabetes induced rabbit model exhibited shrinkage of the
wound, better re-epithelialization, and significant keratinocytes
migration. |
(36) |
| |
Tannic acid |
Tannic acid incorporated
methacrylate chitosan hydrogel and methacrylate silk fibroin hydrogel
were formulated by using the cross-linking process for the treatment
of full-thickness wounds. The results of the in vitro and in vivo
studies demonstrated no toxicity for fibroblast cells (NIH–3T3
cells) and promoted re-epithelization and granulation tissue re-formation
in the mice model, respectively. |
(37) |
| |
Recombinant human collagen
peptide |
The recombinant
human collagen
peptide conjugated chitosan hydrogel was formulated for the treatment
of second-degree burns. The exhibited results of the in vivo study
were promotion of cell infiltration, vessel formation, and complete
wound healing in the rat model. |
(38) |
| Cellulose |
Silver nanoparticles, curcumin,
cyclodextrin, bacterial cellulose |
A silver nanoparticles,
curcumin, cyclodextrins, and bacterial cellulose containing hydrogel
was prepared by implementing a green synthesis and microencapsulation
approach. The optimized formulation displayed broad spectrum antimicrobial
activity against S. aureus, P. aeruginosa, and C. auris (MTT assay). Moreover, the hydrogel also exhibited optimum antioxidant
properties and cytocompatibility with various cell lines. |
(39) |
| |
Bacterial cellulose and
acrylic acid |
A bacterial
cellulose and
acrylic acid impregnated hydrogel was designed by applying an irradiation
approach followed by freeze–drying. The formulation depicted
excellent cell attachment and cell viability during in vitro analysis.
The in vivo experiment results depicted that the formulation acted
as a carrier for the delivery and growth of keratinocytes and fibroblasts
in a full-thickness wound model. |
(40) |
| |
Nonwoven cotton |
A cellulose containing hydrogel
was designed by sol–gel method with reinforcement of nonwoven
cotton as a sustainable wound dressing application. For the improvement
of antibacterial properties of the formulation, titania particles
were embedded. Antibacterial analysis of the formulation by agar disk
diffusion technique displayed the inhibition of the bacterial growth.
Additionally, the hydrogel also displayed optimum biodegradability
and sustainability and was found to be environmentally friendly. |
(41) |
| |
Fenugreek gum |
A
fenugreek gum containing
hydrogel was prepared by forming a hydrogen bond with cellulose. The
hydrogel had characteristics like sufficient mechanical strength,
porous structure, thermal stability, and improved water absorption
rate. The formulation expressed sufficient biocompatibility, prevention
of hemostasis (in vitro), and the process of neovascularization (in
vivo). |
(42) |
| |
Platelet rich plasma |
A platelet rich plasma incorporated
carboxymethyl cellulose containing hydrogel was designed by implementing
the concept of 3D printing technology wherein citric acid was used
as a cross-linking agent. The formulation promoted angiogenesis, stem
cell migration, dermis formation, and rapid cell proliferation in
the diabetic rat model. |
(43) |
| Starch |
Crocus sativus |
A C. sativus petals extract loaded starch-based hydrogel
was designed for atraumatic
wound application. The in vitro study confirmed the growth of keratinocytes,
antioxidant effect, and self-preserving capacity. Furthermore, the
formulation also depicted the antimicrobial effect against S. epidermidis and its utility for the atraumatic
wound. |
(44) |
| |
Gelatin |
The oxidized starch-gelatin-based
hydrogel was prepared as a wound dressing for self-contraction of
the non-invasive wound by implementing the Schiff-based reaction concept.
The resulting formulation revealed high potential and tissue reconstruction
at the site of the wound in the rabbit model as compared to the wound
treated with sutures. |
(45) |
| |
Starch |
The starch containing hydrogel
was prepared by using calcium nitrate tetrahydrate and neodymium(III)
nitrate as a cross-linking agent (ionic cross-linking approach). The
formulation depicted maximum adhesiveness, good stretchability, sufficient
self-healing, degradability, and significant improvement in viscoelastic
properties. The in vitro study of the formulation demonstrated sufficient
cytocompatibility to fibroblast cells and human vascular endothelial
cells, less hemolysis risk, and antibacterial effect. During the in
vivo study, the formulation displayed reduced blood loss at the site
of the wound in the rat model. |
(46) |
| Alginate |
Naringenin |
Naringenin impregnated alginate-based
hydrogel was prepared by using the freeze–drying method. The
resultant formulation depicted good porosity, no toxicity (in vitro),
and re-epithelialization (in vivo) as compared to the wound treated
with gauze. |
(47) |
| |
Nitric oxide |
A nitric oxide releasing
hydrogel was fabricated and characterized to evaluate its effectiveness
against methicillin resistant S. aureus infected wounds. Diethylenetriamine/diazeniumdiolate (DETA/NONOate)
was utilized as NO donor, and alginate was employed for hydrogel synthesis.
The resultant formulation displayed sustained release of nitric oxide
for 4 days. The hydrogel demonstrated significant antibacterial action
against MRSA. The in vivo experimental results for optimized formulation
displayed healed skin structure, increased fibroblasts, and improved
angiogenesis. |
(48) |
| |
α-tocopherol |
α-Tocopherol
impregnated
alginate-based hydrogel was designed by cross-linking approach for
wound healing. The designed composition demonstrated a significant
increase in granulation tissue formation in the full-thickness wound
rat model as compared to the wound treated with gauze. |
(49) |
| |
Zinc alginate, RL QN15 peptide,
polydopamine nanoparticles |
Hollow dopamine nanoparticles
(pro-regenerative agent) with RL-QN15 peptide (pro-healing peptide)
impregnated zinc alginate hydrogel was formulated for the management
of diabetic wound healing. The hydrogel reduced inflammation, enhanced
angiogenesis, increased collagen deposition, and augmented the wound
repair in diabetic mouse full-thickness wound and in vitro skin wound
models. |
(50) |
| Hyaluronic acid |
Collagen-I |
A collagen-I and
hyaluronic
acid containing hydrogel was formulated by in situ coupling of phenol
moieties of collagen-I hydroxybenzoic acid and hyaluronic acid tyramine
via horseradish peroxidase. The in vitro study depicted the prominent
proliferation of human microvascular endothelial cells and fibroblast
cells. Furthermore, an enhancement in the level of VEGF was observed
in human microvascular endothelial cell cultured hydrogel. An in vivo
experiment in full-thickness wound model demonstrated an anti-inflammatory
effect, formation of a new epithelial cell layer on the 7th day of
treatment, generation of fibroblasts cells, and collagen content on
the 14th day of treatment. |
(51) |
| |
Dopamine hydrochloride |
A dopamine hydrochloride
containing hyaluronic acid-based hydrogel was formulated by combining
the carbodiimide conjugation approach and horseradish peroxidase and
hydrogen peroxide cross-linking approach. The in vitro experiment
of the MTT assay depicted significant biocompatibility and zero toxicity
after 24 and 48 h, respectively. The in vivo experiments on a rat
model with liver defect and artery defect demonstrated collagen metabolism,
formation of granulation tissue, and prevention of excessive bleeding
at the site of the wound. |
(52) |
| Gellan
gum |
Adipose-derived
mesenchymal
stem cells |
A gellan
gum and collagen
comprising full-IPN hydrogel housing adipose-derived mesenchymal stem
cells (ADSCs) was fabricated to promote burn wound regeneration. Successful
incorporation of ADSCs into the gellan gum–collagen IPN hydrogel
promoted the fibroblast migration, and also improved its anti-inflammatory
potential. Moreover, early wound closure, complete skin regeneration,
and reduced inflammation were observed after application of the fabricated
hydrogel on murine full-thickness burn wounds. |
(53) |
| |
Tetracycline chloride, silver
sulfadiazine |
Drugs
(tetracycline chloride
and silver sulfadiazine) containing gellan gum microspheres were impregnated
a in double cross-linked, Schiff-based oxidized gellan gum and carboxy
methyl chitosan containing hydrogel designed as a drug delivery system
for effective wound healing. The formulation displayed a significant
antibacterial effect on E. coli and S. aureus during the in vitro experiment. |
(54) |
| |
Ofloxacin, tea tree oil,
lavender oil |
Co-encapsulated
active therapeutic
agents (like ofloxacin, tea tree oil, and lavender oil) containing
gellan gum-based hydrogels were prepared by using solvent casting
ionotropic gelation method for the treatment of full-thickness wounds.
The in vitro experiment of the formulation displayed an antibacterial
effect; the initial burst release of the therapeutic agent (first
24 h) and then controlled release of the therapeutic agent were observed
for the next 48 h. The in vivo experiments depicted wound contraction
after 10 days of treatment. Furthermore, histopathological analysis
confirmed the complete healing of the epidermal layer. |
(55) |
| Collagen |
Succinyl chitosan, curcumin,
collagen |
Nanoencapsulated
curcumin
comprising fish collagen–succinylchitosan composite hydrogel
was fabricated for enhancing wound healing. By employing the ionic
gelation method, curcumin was incorporated into succinylchitosan nanoparticles.
The wound healing potential of the developed hydrogel was evaluated
on Wistar albino rats (subcutaneous wound model). The hydrogel enhanced
the hydroxyproline content and collagen deposition in the wound tissue. |
(56) |
| |
Collagen |
A three-dimensional
collagen-based
hydrogel was designed for rapid recovery of the wound. For in vivo
experiments, a 10 mm excisional wound was created on the dorsum of
diabetic rats. After application of the formulation at the site of
the wound, it was observed that the wound healing rate was faster
than in the group of rats treated with an occlusive dressing. In addition
to this, histological analysis confirmed the re-epithelization and
dermal structure regeneration. |
(57) |
| |
EGF |
EGF receptor conjugated
collagen-based hydrogel was prepared to check its effectiveness in
burn and gastric ulcers. The in vitro study of hydrogel exhibited
noteworthy biocompatibility as an appropriate extracellular matrix
for targeted cells and regenerative cells. During the in vivo experiment,
the hydrogel represented an improvement in ulcer healing capacity
and less scar formation at the site of the wound as compared to hydrogel
alone and controls. |
(58) |
| Elastin |
QK peptide (proangiogenic peptide) |
QK peptide (pro-angiogenic
peptide) and recombinant VEGF containing hydrogels were formulated
by implementing the chemical cross-linking approach. The in vitro
study of formulation displayed the pro-angiogenic activity of QK peptide
because of its binding with VEGF receptor, and new capillary formation.
The result of the in vivo experiment confirmed the stimulation of
the angiogenesis process, enhancement in cellular migration, and subsequent
formation of the capillary structure. |
(59) |
| |
Elastin-derived peptide |
An elastin-based hydrogel
was designed by implementing visible light cross-linking approach.
Cross-linking of methacrylated gelatin and acryloyl-(polyethylene
glycol)-N-hydroxysuccinimide modified elastin was
done. The resultant formulation expressed optimum mechanical properties,
swelling properties, and enzymatic degradation, i.e., biodegradation.
The developed hydrogel attracted neutrophils and macrophages to the
wound site in mice wound model. The elastin-based hydrogel depicted
enhanced angiogenesis, dermal regeneration, and collagen deposition. |
(60) |
| Keratin |
Human hair keratin |
Human hair keratin containing
hydrogel was prepared by implementing a lyophilization process. In
vitro evaluation of formulation confirmed the proliferation and migration
of keratinocytes and fibroblasts. The result of in vivo experiments
confirmed increased re-epithelialization, remodeling, and repairing
of dead tissue at the site of the wound in full-thickness wound mouse
model. |
(61) |
| Albumin |
Glycidyl methacrylate, bovine
serum albumin |
Glycidyl
methacrylate and
modified bovine serum albumin containing hydrogels were designed by
using a photo-cross-linking approach. The result of the in vitro study
depicted the 3D encapsulation of a NIH 3T3 fibroblast cell, improvement
in levels of cell viability, and cell spreading. The in vivo experiment
demonstrated the biocompatible and biodegradable nature of the hydrogel.
Moreover, it was also confirmed that the designed formulation can
deliver the growth factor at the site of the wound in a controlled
manner. |
(62) |
| |
Bovine serum albumin |
Bovine serum albumin containing
pectin–zeolite hydrogels were formulated by using the ionotropic
gelation method (calcium chloride–cross-linking agent; glycerol–plasticizer)
to get controlled release of the albumin at the site of the wound.
In vitro wound healing assay demonstrated a significant cell growth
and migration of fibroblast cells at 48 and 72 h, respectively. |
(63) |
| Fibrin |
Stromal vascular fraction
cells |
A stromal vascular
fraction
cells impregnated fibrin–collagen hydrogel was prepared by
using the chemical cross-linking approach for the treatment of diabetic
wounds. During the in vitro study, the cell migration assay confirmed
the capability of hydrogel for cell migration at low concentrations.
The result of the in vivo study confirmed significant improvement
in the process of angiogenesis. |
(64) |
| |
Nitric oxide |
Nitric oxide loaded fibrin
microparticles impregnated with poly(ethylene glycol)–fibrinogen
containing hydrogel were designed by using the cross-linking approach.
The in vitro study exhibited good biocompatibility and bio-adhesiveness
and confirmed the controlled release of nitric oxide. |
(65) |
