Page 1 of 15 HYDROGELS IN WOUND HEALING Semester Report Submitted in partial fulfillment of the requirements of Study in Advance Topics Submitted by

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HYDROGELS IN WOUND HEALING

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Semester Report
Submitted in partial fulfillment of the requirements of
Study in Advance Topics

Submitted by,
Shafik s. shakil (2017H1460153H)

Under the supervision of
Dr. Swati Biswas
Assistant Professor
Department of Pharmacy

BIRLA INSTITUTE OF TECHNOLOGY & SCIENCE, PILANI
HYDERABAD CAMPUS

April 2018

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ACKNOWLEDGEMENT

I would like to thanks to Dr. Swati Biswas, who gave me the opportunity to learn
and present the topic of Study in Advance Topics on Hydrogel on wound healing

I would also like to thank my friends who helped me during the course of the work.

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Table of content
Contents
ACKNOWLEDGEMENT …………………………………………………………………………………………………………………………… 1
1 Abstract ………………………………………………………………………………………………………………………………………….. 5
2 Introduction …………………………………………………………………………………………………………………………………….. 5
3 Wounds …………………………………………………………………………………………………………………………………………… 5
4 Types of wounds………………………………………………………………………………………………………………………………. 5
4.1 Acute wounds …………………………………………………………………………………………………………………………….. 5
4.2 Chronic wounds …………………………………………………………………………………………………………………………. 6
5 Physiology of wound healing …………………………………………………………………………………………………………….. 6
5.1 Hemostasis ………………………………………………………………………………………………………………………………… 6
5.1.1 Intrinsic pathway ………………………………………………………………………………………………………………… 6
5.1.2 Extrinsic pathway ……………………………………………………………………………………………………………….. 6
5.1.3 Platelet activation ……………………………………………………………………………………………………………….. 6
5.2 Inflammation ……………………………………………………………………………………………………………………………… 7
5.3 Proliferation ………………………………………………………………………………………………………………………………. 7
5.3.1 Angiogenesis ……………………………………………………………………………………………………………………… 7
5.3.2 Fibroblast migration ……………………………………………………………………………………………………………. 7
5.3.3 Epithelialization………………………………………………………………………………………………………………….. 7
5.3.4 Wound retraction ………………………………………………………………………………………………………………… 7
5.4 Remodeling ……………………………………………………………………………………………………………………………….. 7
5.5 Timeline of wound healing ………………………………………………………………………………………………………….. 8
6 Existing treatments for wound healing ………………………………………………………………………………………………… 8
7 Hydrogels ……………………………………………………………………………………………………………………………………….. 8
8 Hydrogels in wound healing ………………………………………………………………………………………………………………. 9
8.1 Amorphous hydrogel …………………………………………………………………………………………………………………… 9
8.2 Impregnated hydrogel …………………………………………………………………………………………………………………. 9
8.3 Sheet hydrogel ……………………………………………………………………………………………………………………………. 9
9 Classification of hydrogels ………………………………………………………………………………………………………………… 9
9.1 Based on Crosslinking in hydrogels ………………………………………………………………………………………………. 9
9.1.1 Crosslinking by chemical reaction of complementary groups ……………………………………………………. 9
9.1.2 Crosslinking by ionic interactions: ………………………………………………………………………………………. 10
9.1.3 Crosslinking by crystallization: …………………………………………………………………………………………… 10
9.2 Based on types of monomers: …………………………………………………………………………………………………….. 10
9.2.1 Homo-polymeric hydrogel …………………………………………………………………………………………………. 10
9.2.2 Co-polymeric hydrogel ………………………………………………………………………………………………………. 10

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9.2.3 Semi-inter penetrating network (semi-IPN) ………………………………………………………………………….. 10
9.2.4 Inter penetrating network (IPN) ………………………………………………………………………………………….. 11
9.3 Stimuli-sensitive swelling-controlled release systems ……………………………………………………………………. 11
9.3.1 environmental stimulus ……………………………………………………………………………………………………… 11
9.3.2 Biochemical stimulus ………………………………………………………………………………………………………… 12
9.4 Based on source ……………………………………………………………………………………………………………………….. 12
10 Methods of preparation of hydrogels …………………………………………………………………………………………………. 12
10.1 Bulk polymerization. …………………………………………………………………………………………………………….. 12
10.2 Grafting to a support. …………………………………………………………………………………………………………….. 12
10.3 Polymerization by irradiation …………………………………………………………………………………………………. 13
11 Polymers used in hydrogel for wound dressing …………………………………………………………………………………… 13
12 Marketed formulations of hydrogel for wound healing ………………………………………………………………………… 13
13 Paper published on hydrogel ……………………………………………………………………………………………………………. 14
13.1 Title …………………………………………………………………………………………………………………………………….. 14
13.2 Introduction………………………………………………………………………………………………………………………….. 14
13.3 Conclusion ………………………………………………………………………………… Error! Bookmark not defined.
14 References: ……………………………………………………………………………………………………………………………………. 15

Table of figures
Figure 1 formation of blood clot ……………………………………………………………………………………….. 6
Figure 2 formation of scab ……………………………………………………………………………………………….. 7
Figure 3 fibroblast migration ……………………………………………………………………………………………. 7
Figure 4 Remodeling……………………………………………………………………………………………………….. 7
Figure 5 Timeline of wound healing ………………………………………………………………………………….. 8
Figure 6 structure of hydrogel …………………………………………………………………………………………… 8
Figure 7 sodium alginate crosslinking ……………………………………………………………………………… 10
Figure 8 semi-interpenetrating network ……………………………………………………………………………. 10
Figure 9 Interpenetrating network …………………………………………………………………………………… 11
Figure 10 PH sensitive system ………………………………………………………………………………………… 11
Figure 11Antigen responsive swelling……………………………………………………………………………… 12
Figure 12 bulk polymerization ………………………………………………………………………………………… 12
Figure 13 marketed formulations of hydrogels in wound healing ………………………………………… 13

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Hydrogels in wound healing.

1 Abstract
The hydrogels are found to be more effective, less expensive method over existing methods as its
ability to keep the wound moist and capability of holding a drug makes it one of the promising
method for the management of wounds. This study includes in depth knowledge about the
wounds including types of wounds, mechanism of wound healing, existing methods which are
widely used in the management of wound healing along with in detail about hydrogels which
includes the types of hydrogels, types of polymers used in hydrogels, detail on types of
crosslinking present in hydrogels, method of preparation of hydrogels, application of hydrogels
in wound healing and detail on existing hydrogel formulations and formulations on which the
clinical trials are going on.
2 Introduction
Hydrogel dressings consist of 90 percent water in a gel base and serves to help monitor fluid
exchange from within the wound surface, in new studies scientists has suggested that the wound
healing is much faster in the case of moist wound as compare to the dry wound because in dry
wound the platelet plug formed during the hemostasis prevent the migration of the epithelial cells
over the wound and which can be prevented in the moist condition wherein by keeping the
wound moist the hydrogel dressing assists the rapid wound healing with less scar as compare to
the dry wound healing and it also protect the wound from infection and can act as a carrier for
the drugs used in wound healing such as antibacterial, growth factors etc. As hydrogel dressing is
the cheaper and more effective compare to the existing treatments for the wound it attracted the
scientists for the research in this field.
3 Wounds
Wound is the Disruption of the integrity of skin, mucosal surfaces or organ tissue. Or it’s an
injury to living tissue caused by a cut or other impact, typically one in which the skin is cut or
broken. Which can be caused by the presence of disease such as gangrene or may be due to
intentional or accidental impact. Wounds are generally healed by the natural healing mechanism
which involves the different phases such as hemostasis, inflammation, proliferation and
remodeling.
4 Types of wounds
Wound has been mainly categorized in to the two types that is acute wound and chronic wound,
the acute wounds generally passed through the healing phase relatively quickly compare to the
chronic wounds as acute wounds takes less than 12 weeks to heal where as chronic wound takes
more than 12 weeks to heal following are the examples of the types of wounds.
4.1 Acute wounds
E.g. surgical incisions, bites, burns.

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4.2 Chronic wounds
E.g. pressure sores, diabetic ulcers, venous stasis ulcers and wounds due to ischemia.
5 Physiology of wound healing
Physiology of wound healing can be classified into four overlapping phases on the basis of the
function of each phase and cellular mechanism involved in that particular phase.
5.1 Hemostasis
This phase starts immediately after the injury and can last for 3-5 days depending upon the
different factors (i.e. age of the patient, dietary factor, disease
condition etc.). the major function of this phase is to prevent
the blood loss after injury by vasoconstriction mediated
through increasing in Ca+ level in cytoplasm. Now this
decreasing in blood flow leads to hypoxia at the site of injury
which stimulate the production of nitric oxide and adenosine
radicles which causes reflux vasodilation. The further blood
loss is prevented through clotting mechanisms (intrinsic
pathway, extrinsic pathway, and platelet activation pathway).
5.1.1 Intrinsic pathway
Intrinsic pathway of the clotting cascade (contact activation pathway) endothelial damage as a
result of tissue injury exposes the sub-endothelial tissues to blood which results in the activation
of factor XII (Hageman factor). This initiates the proteolytic cleavage cascade which results in
the activation of factor X which converts prothrombin to thrombin resulting in the conversion of
fibrinogen to fibrin and the formation of a fibrin plug.
5.1.2 Extrinsic pathway
Extrinsic pathway of the clotting cascade (tissue factor pathway) e endothelial damage results in
exposure of tissue factor (which is present in most cells) to circulating blood. This results in
activation of factor VII and the rest of the extrinsic pathway of the clotting cascade which
eventually results in thrombin activation.
5.1.3 Platelet activation
following activation by thrombin, thromboxane or adenosine diphosphate (ADP), platelets
undergo a change in morphology and secrete the contents of their alpha and dense granules.
Activated platelets adhere and clump at sites of exposed collagen to form a platelet plug and
temporarily arrest bleeding. This plug is strengthened by fibrin and von Willebrand factor as well
as the actin and myosin filaments within the platelets.
Histamine release from mast cells which increases the permeability of vessels and allows the
inflammatory cells around the wound and causes reddening, warming and swelling of wound.
Figure 1 formation of blood clot

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5.2 Inflammation
This stage starts from the 2nd day of injury and can last for 2-
4 days, the main function of this phase is to prevent the
occurrence of the infection at the site of injury by
neutrophils, the neutrophils are attracted towards the site of
injury upon activation of complement cascade, Interleukins
and transforming growth factor ;#55349;;#57143; (TGF ;#55349;;#57143;). This process
also called as chemotaxis. Neutrophils destroys
microorganism by three mechanisms, Phagocytosis,
releasing toxic substances, Producing chromatin and
protease trap.
5.3 Proliferation
This stage lasts for 2 days to 3 weeks and involves the
wound healing through healing cascade and this stage
can again subdivided into 4 parts.
5.3.1 Angiogenesis
In this stage TGF ;#55349;;#57143;, PDGF, FGF, VEGF along with
cytokines induces the endothelial cells to triggers
neovascularization and repairing of blood vessels.
5.3.2 Fibroblast migration
In this stage TGF ;#55349;;#57143; and PDGF stimulates the proliferation of fibroblast and Fibroblast produces
collagen and fibronectin. (pink vascular fibrous tissue replaces the clot at the site of wound also
called as granulation tissue).
5.3.3 Epithelialization
In this stage Epithelial cells migrate from the edges of the wound and form a layer all over the
wound. this process is also called as epithelial-mesenchymal transition (EMT).
5.3.4 Wound retraction
This stage of proliferation involves the contraction of the wound mediated by the interaction
between actin and myosin which pulls the cells closer leads to contraction of wound, with the
rate of 0.75 mm/day.
5.4 Remodeling
This stage can take up to 2 years. This stage
involves the Development of natural epithelial and
maturation of scar tissue and Regaining of structure
similar to unwounded tissue. Wounds never reach to
same level of strength as of unwounded stage. It
reaches to 50% strength in 3 months and maximum
80% strength in long term. During the process of
wound healing the Color of wound changes from
red to pink to gray.
Figure 2 formation of scab
Figure 3 fibroblast migration
Figure 4 Remodeling

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5.5 Timeline of wound healing

6 Existing treatments for wound healing
Some the existing methods for the treatment of wounds includes Surgical treatment, removing
nonviable tissue, Antimicrobial therapy, Dressings and devices Skin substitutes, Tissue sealants
and platelet gels, Cytokines and growth factors but all of them are either an expensive or less or
found to be not effective in certain types of wounds when compare to hydrogels.
7 Hydrogels
Hydrogels are three-dimensional, hydrophilic,
polymeric networks capable of holding large
amounts of water or biological fluids. The networks
are composed of homopolymers or copolymers and
are insoluble due to the presence of chemical
crosslinks (tie-points, junctions), or physical
crosslinks, such as entanglements or crystallites.
These hydrogels exhibit a thermodynamic
compatibility with water which allows them to swell
in aqueous media. The hydrogels can be classified
on the basis of the type of crosslinking, type of monomeric unit used to
make polymeric chain, type of polymeric chains used to make three-
dimensional structure, on the basis of type of stimuli responsive polymer used, bio responsive
hydrogels.
Applications
Hydrogels naturally occur in humans are cartilage, blood clots, mucin (lining the stomach,
bronchial tubes and intestines), and vitreous humor of the eye.
The following are applications of hydrogels:
Soft contact lenses
Figure 5 Timeline of wound healing
Figure 6 structure of hydrogel

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Disposable diapers
Drug delivery (stimulus responsive and un-responsive)
Wound dressings
Provide absorption, desloughing and debriding of necrotic and fibrotic tissue
Component of EEG and ECG medical electrodes
Hemo-compatible (blood compatible) surface for medical devices
Scaffolds in tissue engineering
8 Hydrogels in wound healing
Because of the moisture provided to the wound from the hydrogel dressing, common healing
phases such as granulation, epidermis repair and the removal of excess dead tissue become
simplified. The cool sensation provided by the hydrogel to the wound offers relief from pain for
at least six hours. When hydration is provided for the wound bed, discomfort experienced from
changing the dressing becomes reduced, and the risk of infection also becomes decreased.
Hydrogel dressing for the wound management can be categorized as follows.
8.1 Amorphous hydrogel
A free-flowing gel, distributed in tubes, foil packets and spray bottles
8.2 Impregnated hydrogel
Typically saturated onto a gauze pad, nonwoven sponge ropes and/or strips.
8.3 Sheet hydrogel
A combination of gel held together by a thin fiber mesh.
9 Classification of hydrogels
9.1 Based on Crosslinking in hydrogels
Cross linking can impart visco-elasticity or sometimes pure elasticity in hydrogels. Cross linking
can be chemical and physical but now days chemical cross linking is predominantly used to
ovoid the toxicity of chemical cross linkers. Cross linking can also affect the swelling property
and can be used to prepare stimuli sensitive polymer.
9.1.1 Crosslinking by chemical reaction of complementary groups
Most of the water-soluble polymer has functional groups (mainly OH, COOH, NH2) which can
be used for the formation of hydrogels. Covalent linkages between polymer chains can be
formed by the reaction of functional groups with complementary reactivity, such as an amine-
carboxylic acid or an isocyanate–OH/NH2 reaction, the cross linking involves the chemical
reactions such as condensation reaction, addition reactions, high energy irradiation and using
enzymes.

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9.1.2 Crosslinking by ionic interactions:
Alginate is a well-known example of a polymer that can be crosslinked by ionic interactions.
Alginate is a polysaccharide with mannuronic and glucuronic acid residues and can be
crosslinked by calcium ions. alginate gels are frequently used as the matrix for the encapsulation
of living cells and for the release of proteins. A synthetic polymer that, like alginate, can also be
crosslinked with Ca-ions is poly di (carboxylate phenoxy) phosphazene (PCPP).

9.1.3 Crosslinking by crystallization:
Poly vinyl alcohol (PVA) is a hydrophilic polymer which forms a gel at room temperature with
poor integrity but upon freeze thawing it forms an elastic structure because of formation of PVA
crystals in structure which impart the physical crosslinking in to the structure.
9.2 Based on types of monomers:
9.2.1 Homo-polymeric hydrogel
Homo-polymers refer to polymer networks derived from single species of monomer. It is the
basic structural unit, comprising of any polymer network. Homo-polymers may have a
crosslinked skeletal structure depending on the nature of the monomer and polymerization
technique. Chemically crosslinked PEG hydrogels are a classic example of this class.
9.2.2 Co-polymeric hydrogel
Co-polymeric hydrogels are composed of two types of monomer in which at least one is
hydrophilic in nature. e.g. poly (ethylene glycol)-poly(?-caprolactone)-poly (ethylene glycol)
(PECE)
9.2.3 Semi-inter penetrating network
(semi-IPN)
If one polymer is linear and penetrates
another crosslinked network without any
other chemical bonds between them, it is
called a semi inter penetrating network.
The main advantage of this hydrogels is it
gives modified pore size, slow drug
release and high mechanical strength. E.g.
linear cationic poly allyl ammonium
Figure 7 sodium alginate crosslinking
Figure 8 semi-interpenetrating network

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chloride in acrylamide/acrylic acid copolymer hydrogels.
9.2.4 Inter penetrating network (IPN)
IPNs are conventionally defined as the
intimate combination of two polymers,
at least one of which is synthesized or
crosslinked in the immediate presence
of the other. The main advantage of
IPN is higher mechanical strength and
higher drug loading with compare to
conventional hydrogels. Poly (aspartic
acid) (KPAsp) and carboxymethyl
chitosan (CMCTS) Ac di sol/cross
Carma lose sodium.
9.3 Stimuli-sensitive swelling-controlled release systems
Stimuli responsive hydrogels respond to environmental stimuli and experience unexpected
changes in their growth actions, network structure, mechanical strength and permeability, hence
called environmentally sensitive.

9.3.1 environmental stimulus
9.3.1.1 pH-sensitive hydrogels
PH sensitive polymers are ionized at
specific PH which expand the structure due
to electrostatic repulsion. There are two
types of PH sensitive hydrogels, anionic
and cationic hydrogels the anionic
hydrogel having a functional group such
carboxylic acid or sulfonic acid and
cationic hydrogels has amine functional
group. e.g. poly diethyl aminoethyl
methacrylate (PDEAEMA) and their
copolymer, alginate-N, O-carboxymethyl
chitosan (NOCC).
9.3.1.2 Temperature-sensitive hydrogels:
Temperature sensitive hydrogels are defined by their ability to swell and shrink when the
temperature changes in the surrounding fluid, which means the swelling and deswelling behavior
mostly depend on the surrounding temperature. Temperature sensitive hydrogels into two
different classes, positive temperature sensitive and negative temperature sensitive. Positive
temperature sensitive hydrogels contracts when temperature is fall and expands upon higher
temperature. E.g. N isopropyl acrylamide (NIPAAm), Poly(N-isopropylacrylamide)
Figure 9 Interpenetrating network
Figure 10 PH sensitive system

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(PNIPAAm), Negative temperature sensitive polymers are expanded at lower temperature and
contracted at higher temperature.
9.3.2 Biochemical stimulus
9.3.2.1 Glucose responsive hydrogels
Mainly used for the diabetic patients in which the insulin is loaded into the hydrogel which also
has the bounded glucose oxidase in system when the glucose come into contact with hydrogel it
converted the glucose into gluconic acid and gluconic acid lowers the PH of surrounding which
leads to contraction of hydrogel and insulin is released.
9.3.2.2 Antigen-responsive hydrogels
Antigen-responsive hydrogels are designed by
grafting antigens on hydrophilic polymeric
backbones to deliver biomolecules at a specific
targeted site. In this hydrogel the antibody bounded
on polymeric chain and antigen bounded on
different polymeric chain and they form intrachain
antigen-antibody complex this complex act as
crosslinking in hydrogel and dissolves when another
antigen competitively binds to bounded antibody
which results in breaking of crosslinking and
releasing of drug.
9.4 Based on source
Natural polymers used in hydrogel synthesis: those which are obtain from natural source e.g.
alginate, chitosan, starch, dextran, glucan, gelatin.
Synthetic polymer used in hydrogel synthesis: e.g. PNIPAAM, PVP, polymer composite (MMT)
clay, ZnO nanoparticles, HEMA, HEEMA, HDEEMA, MEMA, MEEMA.
10 Methods of preparation of hydrogels
10.1 Bulk polymerization.
This is a simplest type of technique in which large
number of monomers are added in vessel along
with small number of cross linkers and react in is
activated by the initiators which can be chemical or
radiation. This involves polyaddition (chain
polymerization) type of reaction. The degree of
cross linking in this method is depend upon the
number of cross linkers added.
10.2 Grafting to a support.
Hydrogels prepared by bulk polymerization have
inherent weak structure. To improve the mechanical
properties of a hydrogel, it can be grafted on surface coated onto a
Figure 11Antigen responsive swelling
Figure 12 bulk polymerization

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stronger support. This technique that involves the generation of free radicals onto a stronger
support surface and then polymerizing monomers directly onto it as a result a chain of monomers
are covalently bonded to the support.
10.3 Polymerization by irradiation
Ionizing high energy radiation, like gamma rays and electron beams, has been used as an initiator
to prepare the hydrogels of unsaturated compounds. The irradiation of aqueous polymer solution
results in the formation of radicals on the polymer chains. This radicals attack on different
polymeric chains and form crosslinks. This process yields purest and initiator free hydrogel
11 Polymers used in hydrogel for wound dressing

12 Marketed formulations of hydrogel for wound healing

Natural polymers Synthetic polymers
Collagen
Chitin derivatives and chitosan
Alginic acid and sodium alginate
Starch and starch derivatives
Dextran
Glucan
Gelatin
Poly-N-acetyl glucosamine
Hyaluronic acid or hyaluronan
Bacterial cellulose (BC)
Keratin and silk
Polyurethane
Poly (methyl methacrylate)
Proplast or alloplastics
Poly(N-vinylpyrrolidone) (PVP)
Polyethylene glycol (PEG)
Poly(N-isopropylacrylamide) (PNIPAm)
Nanoparticles composite-polymers
Clay nanocomposite-membranes
Carbon-based materials composite-membranes
Metal oxides composite-membranes
Figure 13 marketed formulations of hydrogels in wound healing

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13 Paper published on hydrogel

Title: A biodegradable hydrogel system containing curcumin encapsulated in micelles for
cutaneous wound healing.
Introduction: The objective of the study is to prepare A biodegradable in situ gel-forming
controlled drug delivery system composed of curcumin loaded micelles and thermosensitive
hydrogel to repair cutaneous wound. Curcumin is believed to be a potent antioxidant and anti-
inflammatory agent. Due to its high hydrophobicity and presence of polyphenolic groups
curcumin was encapsulated in polymeric micelles (Cure-M) with high drug loading and
encapsulation efficiency. Cure-M loaded thermosensitive hydrogel (Cure-M-H) was prepared
and applied as wound dressing to enhance the cutaneous wound healing. Cure-M was prepared
by a one-step solid dispersion method with curcumin and poly (ethylene glycol)-poly (3-
caprolactone) (PEG-PCL) copolymer. In addition, Cur-M loaded thermosensitive poly (ethylene
glycol)-poly (3-caprolactone)-poly (ethylene glycol) (PEG-PCL-PEG) hydrogel composite (Cur-
M-H) was prepared and investigated in detail. Then Cur-M-H composite was assigned for in
vivo wound healing activity test in both linear incision and full-thickness excision wound model.
in the in vivo tests biomechanical tests, biochemical analysis, and histopathological examinations
were conducted to investigate the therapeutic effects of Cur-M-H on cutaneous wound models.

formulation ingredients application
TegaGel calcium salt of alginic acid leg ulcers, pressure sores, ischaemic and
diabetic wounds.
Carrasyn Methylparaben, Panthenol,
Potassium Sorbate, PVP, Sodium
Benzoate, NACL, Sodium Meta bi
sulfite, Triethanolamine
Carrasyn is ideal for dry to low exudating
wounds.
NuGel sodium alginate debrides necrotic tissue
CarraSorb Acemannan HydrogeI™,
Hydroxyethylcellulose,
Polyvinylpyrrolidone.
low to medium exudating wounds for horses,
dogs, cats and other companion animals.

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Discussion: Cur-M with small size, high DL, and high EE was prepared, which was then
encapsulated in thermosensitive PEG-PCL-PEG hydrogel to form Cur-M-H composite. In vitro
tests showed that Cur-M-H composite could convert to a gel at around body temperature, adhere
to the tissue, and sustained release curcumin in an extended period. In the in vivo experiments,
Cur-M-H composite exhibited excellent wound healing activity in both linear incision and full-
thickness excision wound model in rats. Overall results suggested that combination of
bioactivity of curcumin and thermosensitive hydrogel in the in-situ gel-forming composite
promoted tissue reconstruction processes, indicating that Cur-M-H composite is a potential
wound dressing for cutaneous wound healing.
14 Conclusion
At the end the study we can conclude that the hydrogels have a wide range of application in the
management of wound healing. From the formulation perspective hydrogel is found to be a very
good carrier for the drug to target the injury. And availability of various method of preparation
involving less resources makes this formulation more economical, these advantages makes the
hydrogels a good candidate for the wound management.
15 References:

1. Alistair Young, Clare-Ellen McNaught. The physiology of wound healing. Surgery (Oxford)
Volume 29, Issue 10, October 2011, Pages 475-479.
2. N.A. Peppasa,*, P. Buresa , W. Leobandunga , H. Ichikawab. Hydrogels in pharmaceutical
formulations. European Journal of Pharmaceutics and Biopharmaceutics 50 (2000) 27±46.
3. Heather L. Orsted, David H. Keast, Louise Forest-Lalande, Janet L. Kuhnke. Skin: Anatomy,
Physiology and Wound Healing.
4. ChangYang Gong a, QinJie Wu a, YuJun Wang a, DouDou Zhang b, Feng Luo a, Xia Zhao c,
YuQuan Wei a, ZhiYong Qian a,*. A biodegradable hydrogel system containing curcumin
encapsulated in micelles for cutaneous wound healing. Biomaterials 34 (2013).
5. Faheem Ullah a, Muhammad Bisyrul Hafi Othman a, Fatima Javed b, Zulkifli Ahmada,
Hazizan Md. Akil a. Classification, processing and application of hydrogels: A review. Materials
Science and Engineering C 57 (2015) 414–433.
6. Karen Meier ; Lillian B Nanney. Emerging new drugs for wound repair. Expert Opin.
Emerging Drugs (2006) 11.
7. Enas M. Ahmed. Hydrogel: Preparation, characterization, and applications: A review. Journal
of Advanced Research (2015) 6, 105–121.

8. George A. Paleos. What are Hydrogels. Pittsburgh Plastics Manufacturing, Butler, PA