Review

For reprint orders, please contact: reprints@futuremedicine.com

Review of recent research on biomedical

applications of electrospun polymer
nanofibers for improved wound healing

Wound dressings play an important role in a patient’s recovery from health problems, Alaa J Hassiba1, Mohamed
as unattended wounds could lead to serious complications such as infections or, E El Zowalaty2, Gheyath
ultimately, even death. Therefore, wound dressings since ancient times have been K Nasrallah2,3, Thomas J
continuously developed, starting from simple dressings from natural materials for Webster4,5, Adriaan S Luyt6,
Aboubakr M Abdullah6
covering wounds to modern dressings with functionalized materials to aid in the
& Ahmed A Elzatahry*,1
wound healing process and enhance tissue repair. However, understanding the nature 1
Materials Science & Technology
of a wound and the subsequent healing process is vital information upon which Program, College of Arts & Sciences,
dressings can be tailored to ensure a patient’s recovery. To date, much progress has Qatar University, Doha 2713, Qatar
been made through the use of nanomedicine in wound healing due to the ability 2
Biomedical Research Center, Qatar
University, Doha 2713, Qatar
of such materials to mimic the natural dimensions of tissue. This review provides an 3
Department of Health Sciences, College
overview of recent studies on the physiology of wound healing and various wound of Arts & Sciences, Qatar University,
dressing materials made of nanofibers fabricated using the electrospinning technique. Doha 2713, Qatar
4
Department of Chemical Engineering
Keywords: activity • antimicrobial • biomedical • electrospinning • nanofibers & Department of Bioengineering,
• nanomaterials • wound dressings Northeastern University, Boston,
MA 02115, USA
5
Center of Excellence for Advanced
First draft submitted: 20 November 2015; Accepted for publication: 15 December
Material Research, King Abdulaziz
2015; Published online: 8 January 2016 University, Jeddah, Saudi Arabia
6
Center for Advanced Materials, Qatar
University, Doha 2713, Qatar
Background rating bioactive materials, wound dressing *Author for correspondence:
Various materials have been used to cover technology has advanced to a larger ability of Tel.: +974 4403 6808
wounds to prevent contamination and preventing infections and helping the wound aelzatahry@ qu.edu.qa
therefore to provide an appropriate environ- to heal faster [1] .
ment for wound healing. In the past, differ- Researchers are aiming to new heights for
ent materials for wound dressing have been developing wound dressings with properties
used, such as honey pastes, animal fats and and a sophistication unheard of with the
plant fibers. Nowadays, the simplest form of usage of various synthetic and natural poly-
dressings commonly available (e.g., gauzes) mers that are biocompatible and biodegrad-
acts as a simple coverage for the wound from able and can actively support and supplement
mechanical trauma and microbial infection a quick deposition of healthy tissue [2] . More-
while allowing oxygen and fluid exchange over, using such materials and polymers at the
for healing. Hence, they are applicable for nanoscale presents unprecedented properties
numerous superficial wounds that are not such as high-surface area and nanoporosity
infected, or as a support for more advanced valuable for the intended goal [1] . With that
dressings. Another category of wound dress- goal in mind, researchers are using and devel-
ings (e.g., hydrocolloids) has the ability to oping different techniques to create compos-
provide a suitable moist environment needed ites by incorporating fibers with growth fac-
for the wound to heal. Recently, with newly tors, vitamins and other biomolecules known
developed biopolymer materials, process- to encourage a healthy healing process [3–5] .
part of
ing techniques and the ability of incorpo- Nanofibers can be created through different

10.2217/nnm.15.211 © 2016 Future Medicine Ltd Nanomedicine (Lond.) (Epub ahead of print) ISSN 1743-5889
Review Hassiba, El Zowalaty, Nasrallah et al.
techniques, such as self-assembly or phase separation.
However, electrospinning is most frequently chosen
due to its simplicity, cost–effectiveness and versatil-
ity [1] . Electrospun mats have proved to stimulate cell
migration and proliferation, hemostasis, gas perme-
ability, exudate absorption and cell respiration [6,7] . In
this review, recent studies on the electrospinning tech-
niques for developing improved wound dressing are
presented and discussed.
Skin is the largest organ in human body and has
many important roles such as regulation of water, tem-
perature and electrolytes. It also carries a wide vari-
ety of microbiota and skin microbiome which have
gained attention recently. The skin consists of three
layers, namely the epidermis, dermis and hypodermis.
The epidermis is the outer most layer, which works as
a defense line against the entrance of foreign bodies.
It also regulates the temperature and prevents water
loss [8] . This layer consists mainly of a stratified squa-
mous epithelium of keratinocytes, which presents over
90% of the total cells in this layer. The role of keratino-
cytes includes the formation of cytoskeleton filaments
that maintain structural cohesion as well as modula-
tion of the skin during inflammation and repair pro-
cesses [9] . Other type of cells that can be found in this
layer includes antigen-processing Langerhans cells,
pigment-containing melanocytes and Merkel cells for
pressure sensing [10] . The epidermis can be divided
into four sublayers starting with the upper most layer:
the stratum corneum, stratum granulosum, stratum
spinosum and stratum basale [9] .
The dermis, the layer underneath the epidermis, is
composed of connective tissue and is responsible for the
mechanical behavior of the skin. It contains molecules
such as collagens, proteoglycans, elastin and fibronec-
tin that are secreted by fibroblasts, which are found in
an extracellular matrix. Its function involves providing
structural support for the surrounding cells [8] . Three
major cell types are found in this layer, fibroblasts, adi-
pocytes and macrophages. The basement membrane is
a thin sheet of fibers that separates the epidermis and
dermis layers while controlling trafficking of cellular
molecules between the two layers, it also contains a
reservoir for growth factors and cytokines [11] .
The hypodermis, also called the subcutaneous adi-
pose tissue, is the third and deepest skin layer and it
connects the skin to bones and muscles. It is composed
of loose connective tissue with main cell types of adi-
pocytes, fibroblasts and macrophages. The location of
the skin determines the thickness, for instance, the
skin around the eyelids is 0.5 mm thick, which is the
thinnest in the body. On the contrary, skin thickness
on the palms and soles of feet is 4 mm thick, which
is the thickest in the body [12,13] . Hair follicles, sweat
10.2217/nnm.15.211 Nanomedicine (Lond.) (Epub ahead of print)
glands, nerve endings, lymph vessels and blood vessels
can be found throughout the three layers of the skin [8] .
Wounds: principle & types
The term wound is used to describe skin that has
encountered an injury or break in its surface, which
may be caused by thermal, physical or chemical dam-
age [4] . The Wound Healing Society defines a wound
as the result of a disturbance to the present anatomic
structure in the skin and its function [14] . A wound is
considered to be completely healed when the injured
part of the skin returns to its typical functional and
anatomical structure, and resembling its original
appearance within a considerable period of time [14] .
The wound type can be classified according to thick-
ness, morphology, complexity, time elapsed since trauma
occurred, severity and level of contamination. Determi-
nation of wound type is important in guiding the wound
management route. For instance, wounds caused by
sharp objects would result in an insignificant amount of
damaged tissue and low risk of infection. Hence, this
kind of wound can heal by primary intentions and adhe-
sion of the tissue to retain continuity in skin. However,
in primary closure injuries, damage occurs in the micro-
vascular, which increases the risk level of infection that
requires healing by secondary intentions [15] .
The most common classification for wounds is acute
versus chronic. As opposed to the acute wounds, which
are usually healed within 12 weeks of the injury, the
chronic wounds need way more this time [4,16] . Acute
wounds can be caused by a mechanical (e.g., stabbing
by sharp object), thermal, electrical, chemical or radia-
tion while chronic wounds can be the result of a compli-
cation of several diseases (e.g., diabetes or tumors) [17] .
In terms of healing, acute wounds need a support in
protection against infection while chronic wounds
need healing promotion as it lacks the biological signals
required to initiate an appropriate healing process [16] .
Healing process
Wound healing is a biological process which takes
place in the skin, and this healing process has been
reported elsewhere [18,19] . Wound repair is a combina-
tion of orchestrated sequential events in which several
cellular activities are involved throughout the differ-
ent stages of wound healing [20,21] . Although phases of
wound healing overlap, for simplicity, an ideal healing
process can be summarized in four sequential stages
after the wound occurred: hemostasis, inflammation,
proliferation and maturation (Figure 1) [10] .
A wound occurs when skin is punctured result-
ing in death of the tissues in the site. At the site of
injury, fluids from injured blood and lymphatic vessels
escape and accumulate. This site is now susceptible to
future science group
 Electrospun polymer nanofibers for wound healing Review

A Wounding B Hemostasis C Inflammation

Rapid 0–15 min 15 min–day 6

D Proliferation E Maturation
Keratinocytes
Day 6–week 3 Week 3–year 2
Healthy ECM
Clot
Neutrophilis
New keratinocytes
Fibroblasts

Granulation tissue

Figure 1. Schematic representation of the different phases of wound healing. (A) Wound occurring: distribution
of the healthy tissues in the site. (B) Hemostasis stage: the creation of a clot to prevent any further bleeding.
(C) Inflammation stage: penetration of neutrophils to the injured site. (D) Proliferation stage: infiltration of
fibroblasts to the injured site and keratinocytes, and granulation tissue appears. (E) Maturation, the final phase
which may last for years. During the final stage, fibroblasts disappear and the ECM matures.
ECM: Extracellular matrix.
Reproduced with permission from [22] © Royal Society of Chemistry (2013).

bacterial invasion and infection. Hemostasis, reached
within 15 min, aims in producing a clot that will stop
any further bleeding [23] . In this stage, injured vessels
contract, which lower the blood flow to the injured site.
Platelets produce proteins such as fibrinogen, which
causes coagulation of exudates, and fibronectin, which
cleaves into the fibrin and forms a network and per-
forms as an adhesive to bind platelets to each other.
Gathering of these proteins along with other proteins,
such as thrombospondin and vitronectin, and platelets
produce the clot preventing further bleeding [24] .
The inflammatory phase then follows and may stay
up to 6 days [23] . Cells in the injured tissue such as
platelets and mast cells produce chemical signals that
stimulate the dilatation of blood vessels, along with an
increase in capillary permeability, which allows impor-
tant cells, such as neutrophils to reach the injured area.
The neutrophils play an important role in producing
factors that are important in removing foreign objects
and bacteria [24,25] . Monocytes also reach the site of
injury and differentiate into macrophages, which per-
sist for several weeks [23] . The macrophages assist in
removing dead cells, foreign objects and trigger the
production of collagen that influences re-epitheliali-
zation [25] . There are other cells that arrive later on,
about 6 days after the initial injury, which are lym-
phocytes such as CD4 +, CD8 + and dendritic epidermal
gamma/delta T cells. These immune cells also help in
the healing process [23] .
In the proliferation stage, the whole area would be
covered by new epithelial cells (re-epithelialization), a
stage that happens 24–48 h after injury. Keratinocytes
migrate to the wound site and start moving from its
boundaries to the inside until the injured area is closed
with a stratified layer of keratinocytes while secret-
ing enzymes to destroy the temporary-built extracel-
lular matrix [23] . Endothelial cells start migration to
the wound site. This movement is derived by the lack
of nearby endothelial cells, an extracellular matrix
and cytokines, a process that happens 24 h after skin
injury. This migration plays a role in the formation
of new blood vessels, a process called angiogenesis,
by forming tubules which ultimately form new cap-
illaries. The present basement membrane is degraded

future science group www.futuremedicine.com 10.2217/nnm.15.211

Review Hassiba, El Zowalaty, Nasrallah et al.
by matrix metalloproteinases while a new membrane
is formed by stimulating the production of laminin
in endothelial cells [23] . Four days after wound ini-
tiation, the extracellular matrix based on fibrin fades
and is substituted by an extracellular matrix with col-
lagen-based granulation tissue that almost resembles
a healthy extracellular matrix. This granulation tis-
sue contains collagen, blood vessels and fibroblasts.
Growth factors and chemotactic molecules act as a site
signal for the migration of wound healing fibroblasts.
Migrated fibroblasts proliferate and create matrix pro-
teins providing mechanical support for additional cell
migration. Collagen production and cross-linking
account for the mechanical strength of new capillary
beds. During this stage, fibroblasts attach to fibronec-
tin and collagen in the extracellular matrix [23] . Wound
contraction works in promoting the repair by pulling
the edges of the injured site together and it happens
through the help of dendritic epidermal gamma/delta
T cells, 4–14 days after the wound was initiated [25,26] .
Also, within this period of time, myofibroblasts
produce actin and accelerate the closure process [23] .
The maturation stage, also called remodeling,
includes the process of replacing granulation tissue with
fibrous tissue that is remodeled late on to form a scar,
and the enzymatic degradation of collagen into unique
three-quarter- and a-quarter-length parts by the act of
fibroblasts, neutrophils and macrophages [23,26] . By the
third week, collagen levels reach peak values. The stage
of maturation occurs about 3–6 weeks after wounding
and can carry on for months even after wound clo-
sure [23] . It should be noted that there are many factors,
in particular microbial infections, which may result
from improper wound dressings, which could lead to a
delay in the wound healing process.
Wound dressing materials
Ideal dressing
According to the wound type and associated require-
ments to complete the healing process, the most
suitable wound dressing system must be selected,
for which today, we are lacking. Usually, for a rapid
wound healing response, different types of wound
dressing materials can be used. The following char-
acteristics are generally considered as an ideal wound
dressing material regardless of location or need: main-
taining a moist environment for the wound, remov-
ing exudates, preventing microorganisms from enter-
ing the wound and allowing for gaseous exchange.
It should not be toxic or allergenic to the human
body, and it should be nonadherent to mammalian
cells (unless biodegradable) ensuring that its removal
would not cause further trauma. Furthermore, it
should prevent infection while accelerating wound
10.2217/nnm.15.211 Nanomedicine (Lond.) (Epub ahead of print)
healing (Figure 2) . Ideal dressing materials should be
made from clinically available biomaterials, which
need minimal processing to possess antimicrobial
properties [27] .
Types of wound dressings
The selection of wound dressings depends on the type
of wound and on the patient’s need for recovery; hence,
different types of wound dressings have emerged.
Wound dressings can be classified into three groups:
passive, interactive, advanced and bioactive dress-
ings. Passive products, such as gauze, have the least
impact as they only present coverage for the wound
to heal by itself. Interactive materials, such as hydro-
gels and foams, are translucent and possess healthy
water and oxygen permeability. Bioactive materials,
or active wound dressing materials, such as hydrocol-
loids, calcium alginate and collagen, have shown an
ability to effectively heal wounds [1,4,28] . Table 1 pres-
ents examples of the different types of wound dress-
ings, their description as well as advantages and
disadvantages [29–51] .
Nanofibers in wound dressing
Nanofiber mats have drawn the attention of numerous
researches in the wound dressing development field since
they can mimic a natural nanometer dimension of the
tissue they are healing [52] . Nanofiber mats can provide
fine polymeric fibers at the scale of nanometers. Their
structure provides mats with different unique properties,
making them highly tissue compatible to enhance wound
repair in comparison to other conventional dressings. An
ideal wound dressing should have a structure that resem-
bles the natural skin’s structure, and such nanofibers, due
to their physical features, are able to mimic the healthy
extracellular matrix network found in the skin [18,53] . As
mentioned earlier, the extracellular matrix is important
in the repair process as it provides structural support for
cell attachment and proliferation. Therefore, nanofiber
mats could enhance proliferation and improve cell repair
mechanisms [52] . In fact, there are several advantages of
using nanofibers as next-generation wound dressings as
discussed in the following section.
Advantages of nanofibers as wound
dressing
Hemostasis
Nanofibers produced by electrospinning consist of
small interstices and a large surface area to volume
ratio. Due to their biologically inspired features, those
physical features allow for improved hemostasis at
the injury site, and hence, this mat may substitute for
the addition of hemostatic agents which would have
adverse effects in the body [52] .
future science group
 Electrospun polymer nanofibers for wound healing Review

Minimizes
scarring
Provides scaffold
for cell growth

Strengthens new
Forms barrier
tissues
against infection

Provides protein for

Encourages
healing
natural blood
clotting

Absorbs fluids from

inflammation

Blocks nerve endings

to reduce pain

Figure 2. Illustration showing the required properties of an ideal wound dressing. An ideal wound dressing
should have the ability to: first, minimize scarring of the tissue after healing; second, support and strengthen
newly formed tissue; third, deliver nutrients needed for wound healing such as proteins; fourth, absorb excess
exudates from inflammation; fifth, minimize pain from the wound by blocking the endings to reduce pain; sixth,
stimulate clot formation; seventh, protect the wound from microorganisms and foreign particles and eighth,
provide a road map for tissue regeneration.
Reproduced with permission from [27] © Elsevier (2011).
Absorption of exudates from the wound Drug-controlled release
Absorption of exudates is one of the main objectives Different fabrication techniques for making nanofibers
for an ideal wound dressing material. Due to the same allow for the addition of drugs to be released for topical
physical properties of having small interstices and applications. The type of drug loaded can be chosen
a high surface area to volume ratio, nanofibers can according to the wound need for improved healing.
absorb between 18 and 213% more water than films Examples include using one or more antibacterials,
made from the same polymers. This would also help antifungals, growth factors and vitamins [52] .
prevent wound desiccation [52] .
Flexibility in the dressing mat
Maintaining a moist environment Wound dressings should provide flexibility to the
& permeability patients upon applying and comfortability after place-
Electrospun mats consist of nanofibers, which resemble ment, and these nanofiber dressings can provide the
a mesh and provide a moist environment for cell res- adaptability and compliance needed [52] .
piration and, eventually, for cell proliferation and via-
bility. The porous nature of such mats not only works Scar-free
against bacterial infection due to a small pores size but Although not easy to achieve, researchers have
it also maintains a high gas permeation, which protects been conducting studies to create nanofiber dress-
against tissue dehydration [52] . ings to cause minimal scarring. Martindale created

future science group www.futuremedicine.com 10.2217/nnm.15.211

Review Hassiba, El Zowalaty, Nasrallah et al.

Table 1. Examples of different types of dressings, their description and weakness.

Wound dressing type Example Description
Passive Gauze Made of cotton fibers. It is cheap and
readily available
Interactive Hydrogel Made of cross-linked polymers
(e.g., starch, cellulose) or polysaccharide
derived from plant or animals
It is suitable for dry or low exudate
wounds as it provides moisture, absorbs
exudate, can be left on the wound site
for several days, will not cause trauma to
remove if used appropriately and helps in
autolysis of dead tissue
Semipermeable Made of plasticized polyvinyl polymer
film and have nonporous structure
It keeps injured site moist, allows for
visual checkup and stops bacterial
passage to wound
Advanced Hydrofibers Contains sodium carboxymethyl cellulose
Used for medium/heavy exudates,
maintains a moist environment for
wound and it can be left on the wound
site for several days
Calcium Made of polymers extracted from
alginates seaweeds
Highly effective for wounds with
exudates and deep-cavity wounds and
aids in preventing maceration
Hydrocolloid Made of polyisobutylene,
carboxymethylcellulose, pectin, sodium
and gelatin. Offers a moist environment
that is deprived from oxygen
Antibacterial wound Iodine dressing The most widely used forms are
dressing iodophors povidoneiodine or cadexomer-
iodine dressings. Has antiseptic effect
against broad spectrum of bacteria, fungi
and viruses
Silver dressing Silver in form of metal, ion and
nanocrystal has been incorporated
in various dressing materials, such as
hydrofibers and hydrocolloids
Weaknesses Ref.
Fibers may shed, bacteria may [29–31]
migrate from the sides, and
traumatic to remove
Requires secondary dressing [32–36]
to adhere in place, not
recommended for heavy
exudate wound as it may cause
maceration
Will not work against [29,36–
maceration 38]
Requires secondary dressing to [36,39]
adhere in place
Requires secondary dressing [37,40–
to adhere in place, not 42]
recommended for dry wounds,
requires moisture to avoid
damage to the site after
removal and fibers may shed
In an environment with a [29,43–
heavily exudate, hydrocolloid 44]
will not work against
maceration in heavily exuding
wounds
Has a cytotoxic effect against [45–47]
cells such as keratinocytes and
leukocytes that hinder the
wound healing process. Hence,
it is appropriate for a
short-term application only
Studies have been conducted [48–51]
to investigate the possibility of
causing toxicity for patients

electrospun wound dressing materials that immedi- Nanofibers fabrication techniques

ately promoted normal skin growth because the bio-
degradable fibers provided a suitable road map for
tissue healing. Electrospun nanofibers have a struc-
ture that mimics the skin; therefore, these nanofiber
dressing mats would enhance compatibility of blood
and, ultimately, enable wound repair and tissue
regeneration [54] .
Nanofibers are threads which have a diameter at the
nanoscale and are created from polymers treated in a
specific way. The resulting properties of large surface
to volume ratio and changes in surface characteristics
give these nanofibers the capability to develop super-
fine structures. The ability to create a composite and
upload antibiotics [55] , vitamins [3,4] and/or growth

10.2217/nnm.15.211 Nanomedicine (Lond.) (Epub ahead of print) future science group


hormones [5] into nanofibers broadens the possibility of
their use in biomedical fields for further development.
Fabrication of nanofibers can be carried out through
different techniques, for instance, self-assembly, tem-
plate synthesis, phase separation, force spinning and
electrospinning. Electrospinning, however, has proven
to be the most cost-effective to make nanofibers with
an easy to carry out the process [56] . Therefore, recent
studies have used electrospinning to create nanofibers,
and consequently, the focus of this review paper is on
electrospinning.
Self-assembly
In self-assembly, small molecules are the basic build-
ing blocks that form nanofibers when added together.
The building blocks are organized around a common
center where extension in the plane results in the lon-
gitudinal axes of the nanofibers. This technique is con-
sidered to be a ‘bottom-up’ technique, where the final
structure is encoded in the form of small blocks. The
shape and properties of the nanofiber are controlled
by the molecules and intermolecular forces that result
in an attraction between the building blocks bringing
them together. For the process to be carried out, stan-
dard laboratory equipment is needed, which is limited
to certain polymers. Examples of polymers that can
be created via this method are triblock copolymers of
peptide amphiphile and dendrimers [57,58] .
Phase separation
In phase separation, the polymer is stored as a homo-
geneous solution with a desired concentration in a
refrigerator to create the gel form of the polymer.
The obtained gel form, the material, is then soaked
in distilled water to allow for solvent exchange. After
removal from the water solution, the gel is dried by a
filter paper and placed in a freeze-dryer, which yields
the nanofiber matrix. Phase separation is considered a
relatively simple process but it is restricted to the labo-
ratory scale only [57] .
Electrospinning
Unlike conventional methods, such as dry-spinning
and wet-spinning, which can be used to create fibers,
electrospinning depends on electrostatic forces and the
differences in voltage between the tip of the needle and
the collector, rather than mechanical forces, to stretch
the solution and create fibers. However, unlike con-
ventional methods, pulling the solution to form fibers
will continue to provide enough solution being fed to
the syringe, which leads to a collection of a fibrous mat
composed of distributed continuous nanofibers [59] .
A typical electrospinning setup consists of basically
three main components: a syringe with a spinneret
future science group
Electrospun polymer nanofibers for wound healing Review
tip, a high-voltage power supply and a fiber collec-
tor (Figure 3) . The high-voltage power supply is used
to create an electrically charged jet of polymer solu-
tion out of the spinneret tip. Under a high voltage, a
cone-shaped droplet of the polymer solution is formed
and directed toward the counter electrode, which is
attached to the collector. A further increase in the volt-
age causes the droplet to stretch slowly, and upon an
additional increase in voltage, a jet is formed from the
droplet creating the narrow fibers to solidify and rest
on the collector [60] .
Electrospinning working parameters
There are several controllable synthesis parameters,
which affect fiber formation during the electrospin-
ning process. These can be categorized into three main
groups: solution, processing and ambient parameters.
Control of these parameters will allow for the fabri-
cation of nanofibers with a desired morphology and
diameter [61] .
Solution parameters
Concentration
For the fabrication of fibers to occur, the concentration
of the solution must be above a minimum point called
the critical point. Above this minimum point, fibers
will be observed along with the presence of beads.
As the concentration of the solution increases, beads
start disappearing and spindle-like fibers are obtained.
Increases in concentration cause spindle-like fibers to
disappear and uniform fibers to form, which is the
optimal concentration of the solution. More concen-
tration increases result in the obstruction of the solu-
tion ejection continuity from the tip of the needle and
larger fibers are formed [62,63] .
Molecular weight
Greater molecular weight of the polymer causes entan-
glements of polymer chains in solution, and thus solu-
tion viscosity increases. The molecular weight of the
polymer influences different properties such as rheology,
viscosity, surface tension and conductivity along with the
electrospun polymer morphology. It has been observed
that low molecular weight polymers in solution are likely
to form beads rather than smooth fibers. Increases in
molecular weight cause the formation of smooth fibers.
Further increases in molecular weight of the polymer in
the solution result in fibers with larger diameters [62,64] .
Viscosity
Viscosity is another factor that affects nanofiber morphol-
ogy and it is linked to the concentration of the solution
and the molecular weight of the polymer. A low solution
viscosity gives discontinuous fibers, and increasing the
www.futuremedicine.com 10.2217/nnm.15.211
Review Hassiba, El Zowalaty, Nasrallah et al.
viscosity will improve the fiber morphology until smooth
and continuous fibers are obtained at an optimum viscos-
ity. A further increase in viscosity leads to hard ejection
of the solution from the tip of the needle [65,66] .
Surface tension
Surface tension is related to solvent composition of
the solution and different solvents result in differ-
ent surface tension. High surface tension leads to
instability of the jets and the formation of droplets
as electrospray rather than electrospinning processes.
Therefore, in order to obtain fibers without beads, it
is required to reduce the surface tension of the solu-
tion. It should be noted that lower surface tension
does not always work to obtain nanofibers, but rather
setting the lower and upper boundaries of the elec-
trospinning window in which nanofibers are obtain-
able [62,67–68] .
Conductivity/surface charge density
Solution conductivity is governed by the type of poly-
mer and solvent, and ionizable salts. With an increase
in electrical conductivity, the diameter of the nanofi-
bers decreases while a decrease in electrical conduc-
tivity results in beads because the electrical forces
will be insufficient enough to cause elongation of
the jet to create uniform fibers. It has been observed
that an increase in the conductivity of the solution
tends to form thinner fibers and that the jet radius is
Figure 3. The schematic illustrates the electrospinning technique. The setup consists of (A) a spinneret containing
the polymeric solution, (B) a high-voltage power supply that is connected to the spinneret and the collector and
(C) a collector. (D) Shows a scanning electron microscopy image of a collected electrospun nanofiber.
10.2217/nnm.15.211 Nanomedicine (Lond.) (Epub ahead of print)
inversely proportional to the cube root of the electrical
conductivity of the solution [62,66] .
Processing parameters
Distance between the tip to the collector
The distance between the tip of the needle and the col-
lector affects the morphology of the fibers. Long and
short distances between the tip and the collector will
result in bead formation; hence, an optimal distance is
required. It has been found that the shortest distance,
which allows sufficient time for the fibers to dry before
reaching the collector, is needed [69,70] . However, others
have reported that distance is not as vital in its effect
on fiber morphology as the other factors [71] .
Flow rate
The flow rate of a polymer solution is considered to be
another important factor during the electrospinning
process [72] . Commonly, a low flow rate is preferred
because the solution will have sufficient time to polarize.
A high flow rate results in beads with larger diameters
due to low stretching forces and insufficient drying time
before the ejected polymer reaches the collector [73,74] .
Types of collectors
The collectors serve as the recipient upon which the fab-
ricated nanofibers will rest and get collected. A common
collector is aluminum foil, but with this type of collector,
it could be difficult to separate the nanofiber membrane
future science group
 Electrospun polymer nanofibers for wound healing Review

from the collector. Other types have emerged, such as
pins [75] , gridded bars [76] and rotating rods/wheels [77] .
Wang et al. used two types of collectors to obtain elec-
trospun nanofibers: aluminum foils and a wire screen.
They observed that using the wire screen collector was
not as consistent as that of the aluminum foil. It was
shown that a smaller collection area has a negative effect
on the collection and beads were observed [78] .
Applied voltage
Voltage is a critical factor during the electrospinning
process. Ejection of charged jets can only occur when
the applied voltage is higher than the threshold volt-
age [66] . However, the influence of applied voltage on
the diameter size of the nanofibers is a debatable issue.
Reneker and Chun showed that the electric field did
not affect the diameter of polyethylene oxide [79] while
Zhang et al. showed that the diameter of electrospun
poly(vinyl alcohol) (PVA)/water formed under a higher
voltage gave rise to larger diameter fiber.
Ambient parameters, such as humidity and tem-
perature, can also affect the morphology and thickness
of the fibers. In a study relating the temperature and
diameter of polyamide-6 electrospun fibers, increases
in temperatures resulted in thinner fiber diameters
which were related to the low viscosity of the solution
at the high temperature [80] . Another study investigated
the relationship between humidity and electrospun
polystyrene and showed that increases in humidity led
to a porous appearance on the surfaces of the fibers [81] .
Modified electrospinning technique
Coaxial electrospinning is a modified technique of the
original simple electrospinning setup. In this method,
two different polymer solutions or a polymer solution
and a therapeutic agent reservoir can be electrospun
via one setup while being loaded by separate objects
(Figure 4) . This method creates core–shell fibers, where
the core is the reservoir and the shell is the polymer [1,82] .
This modified technique is mostly useful in creating
nanofibers that encapsulate a therapeutic agent in its
core, hence, avoiding an initial burst release effect of
the content. The core content would be able to escape
from the fibers through diffusion or after the fiber deg-
radation [65] . A similar, more advanced technique is the
triaxial electrospinning, which allows for the creation
of trilayer-structured nanofibers. Each of the three lay-
ers is based on the same polymer matrix; however, each
can be loaded with different compositions [83] .
Another technique that allows the fabrication of two
compartments is the side-by-side method. However,
unlike core–shell technique that has the compartment
in interior–exterior relationship, side-by-side electros-
pinning permits both compartments to be exposed to
its surroundings [85] .
Composition of wound dressing mats
Natural materials
Chitosan
Chitosan is a polysaccharide derived from chitin
which is the second most abundant polysaccharide in
the world, ranked right after cellulose. Chitosan is a
renewable resource representing a principal component
in the exoskeleton of sea crustaceans, such as crabs and
shrimps, and it can be found naturally in microorgan-
isms, such as yeast and fungi. Furthermore, chitosan is
a biodegradable, biocompatible polymer with antibac-
terial properties and wound healing abilities. It has also
been proven to achieve hemostasis and promote tissue
regeneration [27] .

A B
Fiber
Vitamins
Core-shell 1000 nm
Coating
Drug

150 nm
Natural
Growth compounds
factors 222 nm
Anesthetics

Figure 4. Illustration of core–shell technique and a scanning electron microscopy image of a resulted nanofiber.
(A) Fabrication of nanofibers via electrospinning and examples of compositions that can be involved in core–shell
nanofiber production to help in the wound healing process. Reproduced with permission from [1] .(B) Core–shell-
structured nanofibers produced from coaxial electrospun polyethylene glycol and polydodecyl thiophene with the
latter polymer being encapsulated in the core.
Reproduced with permission from [84] © John Wiley and Sons (2014).

future science group www.futuremedicine.com 10.2217/nnm.15.211

Review Hassiba, El Zowalaty, Nasrallah et al.
Electrospinning of pure chitosan is difficult because
it is a polycationic in nature and can be of high viscos-
ity in solution, making it difficult to electrospin; hence,
it needs toxic or highly concentrated acidic solvents to
reduce its viscosity [86,87] . These conditions make the
processing of pure electrospun chitosan undesirable
in biocompatible-related applications. Therefore, to
obtain biocompatible nanofibers, chitosan has been
blended with other readily spun polymers, such as
PVA, which is one of the most common medical poly-
mers used today. Nevertheless, this cospinning repre-
sents a limitation, as only a limited concentration of
chitosan can be integrated into polymers [88] .
Naseri et al. have used chitosan along with another
polymer, polyethylene oxide, to fabricate a novel wound
dressing mat. Several characteristics of the electrospun
mat were investigated, such as structural morphol-
ogy, mechanical and thermal properties, water vapor
permeability and cytocompatibility. They decided to
substitute the usual cross-linking reagent, glutaralde-
hyde, which is used to increase mechanical properties
of organics in many applications with a lower cytotox-
icity reagent, genipin. The fabricated dressing showed
moisture stability and high tensile strength along with
compatibility toward adipose cells up to 7 days after
promoting this mat as a potential candidate for wound
dressing applications [89] .
Silk fibroin
Silk is a natural fiber acquired from insects, spiders and
silkworms, and it consists of two types, fibroin and
sericin. Silk fibroin (SF) is a hydrophobic protein that
has been studied for medical applications because of its
desired properties: biocompatibility, biodegradability,
minimal inflammatory reaction, adherence, absorp-
tion of exudates and excellent mechanical properties.
Medically, it has been used as artificial ligaments of
blood vessels and skin grafts [90–92] .
Shahverdi et al. investigated electrospun fibers of SF
and the possibility of enhancing its fiber properties by
adding another polymer, poly(lactide-co-glycolic acid)
(PLGA). SF/PLGA blends with different concentra-
tion ratios and their effects on wound healing rate were
studied. SF/PLGA scaffolds, with a ratio of 1:2, showed
superior properties in comparison to pure SF and
SF/PLGA with 1:1 ratios; in that SF/PLGA (1:2) had
improved tensile mechanical properties. In comparison
to the other tested blends and controls, SF/PLGA (1:2)
significantly increased the attachment and proliferation
of mouse fibroblasts (L929) and largely decreased the
wound area in an excision wound model in diabetic rats,
resulting in a most prominent wound healing effect [93] .
In another study, SF was incorporated with poly-
ethylenimine (PEI) in order to create antibacterial
10.2217/nnm.15.211 Nanomedicine (Lond.) (Epub ahead of print)
bionanotextiles. Bionanotextiles refer to a new genera-
tion of wound dressing material that possesses unique
properties (such as a controlled release of therapeutic
agents and highly improved cell adherence and prolif-
eration) due to their very high surface area to volume
ratio. Therefore, it is more efficient in comparison to
the usual wound dressing material such as hydrocol-
loids and hydrogels. The resulting blend showed strong
antibacterial activities against Staphylococcus aureus
and Pseudomonas aeruginosa with an ability to prevent
bacterial adhesion for a long period of time [94] .
Gelatin
Gelatin is a natural polymer derived from collagen and
has natural abundance; hence, it has the composition
and properties of collagen [95] . It is a biodegradable poly-
mer used in food, cosmetics and the medical field [96] .
The product of gelatin can be in the form of a film,
nanoparticles or porous hydrogel. Gelatin nanofilms
can be obtained through electrospinning. However,
gelatin is a polyelectrolyte polymer that has ionizable
groups, and it has strong hydrogen bonding leading to
a 3D macromolecular network, reducing the motion of
gelatin chains [97] . Hence, the electrospinning of gela-
tin alone is poor [98] . Solvents (such as 2,2,2-trifluoro-
ethanol [99] , formic acid and acetic acid) can be used
for the electrospinning of gelatin [100] . To increase the
stability of electrospun gelatin, studies were performed
on the cross-linking of the fibers by different chemicals
such as glutaraldehyde vapor [100,101] or hexamethylene
diisocyanate [102] .
Lu et al. aimed to produce gelatin in mass amounts
using spiral-electrospinning instead of a known sin-
gle-needle electrospinning, which yielded more than
usual finer nanofibers. Two methods of cross-linking
were used, vapor- and liquid-phase glutaraldehyde.
Examination of nanofibers using a scanning electron
microscope (SEM), transmission electron microscope
(TEM) and mechanical testing showed differences in
the fabricated nanofibers, and evenly cross-linked fibers
with higher tensile strength and better morphology
were obtained from liquid-phase glutaraldehyde [103] .
Polymers
Poly(vinyl alcohol)
PVA is a synthetic polymer that is one of the oldest
and most frequently used hydrogels with good biocom-
patibility properties. It has been involved in advanced
biomedical applications such as wound dressings, [104]
drug delivery systems [105] and artificial organs [106] .
When it comes to wound dressing applications, PVA
cannot be used on its own, as it has inadequate elas-
ticity, and lacks the required hydrophilicity. Hence,
blends of PVA with polysaccharides or some synthetic
future science group

polymers to produce hydrogels are beneficial due to
their abundance, ease of modification or derivitization
and usually have good biocompatibility properties [107] .
PVA/gum tragacanth
Gum tragacanth (GT), a natural gum exuded from
plants, is an acidic biopolymer that consists of two
polysaccharides: tragacanthin, which is water soluble
with high molecular weight, and a complex of methox-
ylated acids, which is water insoluble with an ability
to swell and form gels. Medically, GT is considered
as a biodegradable, biocompatible polymer that does
not cause allergies, mutation or toxicity. Its poten-
tial application has been studied, for example, as an
immobilizing agent in viral assays [108] , in burn wound
dressings [109] and in drug-delivery systems [110] .
Ranjbar-Mohammadi et al. prepared PVA/GT
nanofibers and evaluated their application as a wound
dressing [111] . Different GT concentrations blended
with PVA were first optimized to obtain uniform
beadless nanofibers. During preparation, saturated
glutaraldehyde vapors were used to improve water
resistance. Antibacterial and cell proliferation assays
of the PVA/GT nanofibers were determined. PVA/
GT nanofibers showed antibacterial activity against
Pseudomonas aeruginosa, Gram-negative bacterium
that contaminates wounds causing severe infections
and it is characterized by multiple drug-resistance
properties [111] . However, no antibacterial activity
against Gram-positive bacteria was detected. Further-
more, MTT assays showed that these nanofibers are
biocompatible and possess cell viability properties [111] .
PVA/keratin
Keratin is a natural protein with disulfide bonds and
a structure rich in cysteine. Keratin can be classified
into three types: α-keratin (found in animal hair, wool
and hooves), β-keratin (found in claws, feathers and
beaks) and γ-keratin (found in human hair). Pure kera-
tin, however, has poor mechanical properties. Hence,
the addition of other polymers can enhance properties
of keratin and ease its processability while maintain-
ing the advantages of keratin, such as biocompatibility,
biodegradability and natural abundance [112] .
In an attempt to blend PVA with keratin, Park et al.
prepared and characterized aqueous keratin that was
extracted from human hair and was blended with
PVA to fabricate nanofibers by electrospinning. PVA
(10 wt%) was blended with different weight concen-
trations of keratin under a controlled acidic pH. Since
PVA is a highly hydrophilic polymer, PVA nanofibers
were cross-linked using glyoxal (with different concen-
trations) to improve water resistance. Figure 5 shows
the SEM images of human-based-keratin/PVA nanofi-
future science group
Electrospun polymer nanofibers for wound healing Review
bers with different weight fractions of the cross-linker.
Electrospinning conditions were set to 18 kV with a 16
cm working distance and nanofibers 100–300 nm were
obtained. Different concentrations of glyoxal affected
its morphology, thermal analysis and antibacterial
results. With an increase in the cross-linker amount,
homogeneous and bead-free nanofibers were obtained
and more thermal stability was reached. Human-
based-keratin/PVA nanofibers with the smallest and
intermediate content of glyoxal showed antibacterial
effects against S. aureus while the highest concentra-
tion did not show any antibacterial effect. This could
be due to the strong interaction between the molecules
of PVA and keratin with glyoxal. On the other hand,
the fibers did not show antibacterial behavior against
Escherichia coli, which could be attributed to the dif-
ference in cellular content between Gram-positive and
Gram-negative bacteria [113] .
Poly(vinyl pyrrolidone)
Poly(vinyl pyrrolidone; PVP K-30) has been used as
a film-forming agent and a viscosity-enhancement
agent and is considered an essential element in deter-
gents, paints and biological engineering. Due to its low
chemical toxicity and biocompatibility, PVP K-30 is
widely used in the commercial products and in the cos-
metic market, for example, hair-spray reagents, sham-
poos, eye makeup, lotions, sunscreen and skin care
products [114] . Furthermore, PVP can react with iodine
to generate a chemical compound with iodophor
characteristics that is utilized as an antiseptic mate-
rial [36,115] . The PVP-iodine complex (PVP-I) works
as an iodophor that releases active iodine, an effective
antimicrobial agent [116] .
Gökmeşe et al. synthesized and studied nanofi-
bers characteristic of the PVA/PVP blend and used
this blend to develop another three kinds of nanofi-
ber mats: PVA/PVP with 5% and 10% chitosan and
PVA/PVP-iodine fibers. The addition of chitosan to
the polymer-blended solution caused thinner fibers
due to the increase in solution viscosity and nanofi-
ber conductivity. The addition of iodine affected the
morphology of the nanofibers as it had a higher ten-
dency to form beads due to the relatively lower con-
ductivity of the nanofibers [114] . Aytimur et al. prepared
and investigated electrospun nanofibers consisting of
PVA/PVP-I with the addition of two other polymers:
PVA/PVP-I with Poloxamer 188 and PVA/PVP-I with
chitosan. Poloxamer 188 (P188) is a triblock copoly-
mer that consists of poly(oxypropylene) as a central
hydrophobic chain and a poly(oxyethylene) hydro-
philic chains bordering the central chain [117] . P188 has
been used as therapeutic reagent to reduce viscosity in
the blood before transfusions and in over the counter
www.futuremedicine.com 10.2217/nnm.15.211
Review Hassiba, El Zowalaty, Nasrallah et al.
1 µm
1 µm
Figure 5. Scanning electron microscopy images for poly(vinyl alcohol) and human-based-keratin nanofibers.
Images show (A) keratin nanofibers blended with poly(vinyl alcohol), (B) after dipping fabricated fibers in 3 wt%
glyoxal, (C) after dipping fabricated fibers in 6 wt% glyoxal and (D) after dipping fabricated fibers in 12 wt%
glyoxal.
products such as toothpaste and laxatives. Lee et al.
documented the ability of P188 to repair the damaged
membranes of skeletal muscle cells [118] . In a study by
Aytimur et al., the addition of both chitosan and P188
increased the thermal stability of the PVA/PVP-I mat.
The morphological analysis showed that the addition
of chitosan resulted in a more compact and fibrous
structure with a fiber diameter of 374 nm while P188
resulted in a more porous and beaded structure with a
fiber diameter of 489 nm [117] .
Poly(acrylic acid)
Poly(acrylic acid) (PAA) is obtained through photoini-
tiated or γ-radiation-initiated polymerization of acrylic
acid (AA). PAA is a water-soluble biocompatible poly-
mer that has been used as a carrier for proteins, enzymes
and biologically active substances, and its super absor-
bent capability allows it to be used in applications
involving the water-soluble drugs [119,120] . A PVA/PAA
nanofiber mat has been fabricated by Aytimur and Uslu
(2014). The blend was used as the primer solution and
other polymers were added creating three additional
nanofibers mats: PVA/PAA/PVP, PVA/PAA/PVP-I
and PVA/PAA/chitosan. It was found that PVP and
PVP-I increased the thermal stability of the PVP/PAA
10.2217/nnm.15.211 Nanomedicine (Lond.) (Epub ahead of print)
1 µm
1 µm
nanofibers. The morphology of the PVA/PAA nanofi-
bers was linear with beadless fibers with a diameters
of 485 nm. PVP/PAA/chitosan, PVA/PAA/PVP and
PVA/PAA/PVP-I resulted in smaller diameter of 237,
139 and 279 nm but beads were formed [116] .
Aytimur et al. carried out another study where
they prepared and examined two polymer blends
PVA/polyethylene glycol (PEG) and PVA/polypropyl-
ene glycol (PPG) and examined their biological proper-
ties. PEG and PPG are soluble in water with low toxic-
ity and antigenicity. The importance of PPG and PEG
additions relies on the ability of PPG to act as plasticizer
and the ability of PEG to act as an anticross-linking
agent since sterilizing wound dressing materials by
ionic radiation results in covalent bonding of polymeric
chains. PVA/PEG nanofibers with a different concentra-
tion showed either agglomeration of very porous fibers
with irregular fiber shapes. The same was observed for
PVA/PPG except for PVA/50% PPG where the fibers
were beadless and varied from ribbon-like to uniform
fibers with a mean diameter of 1.082 μm [121] .
Antimicrobial agents
A wide range of Gram-positive and Gram-negative
bacteria may contaminate wounds leading to wound
future science group

infections. If left untreated, wound infections may
cause septicemia and further complications, which may
lead to fatality depending on the site of wound infec-
tion. Electrospun mats may provide a solution because
these fibers have a porous structure that is suitable for
applications in wound dressings and drug delivery [55] .
Ciprofloxacin is a fluoroquinolone semisynthetic
antibiotic of wide applications in wound healing [122] .
In a study done by Jannesari et al., a new electrospun
nanofiber mat for controlled drug release was devel-
oped to enhance the wound healing rate. A nanofiber
composite containing PVA and poly(vinyl acetate) was
prepared and loaded with ciprofloxacin. For the first
time, such a composite was successfully prepared using
electrospinning. It was noted that introducing the drug
into the solution significantly decreased the viscosity of
the solution and the average diameter of the fibers. The
kind of polymer and the quantity of the loaded drug
affected the in vitro studies such as the swelling test,
rate of drug release and initial burst. The thickness of
the fabricated nanofiber mat strongly affected the rate
of drug release and initial burst [55] . The addition of
antibiotics or antimicrobials to the fabricated wound
dressings is of an important advantage for fighting
wound infections. Nevertheless, loading drugs needs
to be adjusted for different variables such as type of
wound and the rate of drug release to reach the desired
therapy [123] . An important drawback is the initial
effect that is always accompanied with drug release,
which is high local drug concentrations that harm the
cells [124] . The ideal drug-loaded mat wound dressing
should be a smart device with the capability to treat
different kinds of wound. It should be able to moni-
tor the conditions of the cells and, only when needed,
allows release of the therapeutic agent with an optimal
delivery profile [1] .
Vitamins
Fan et al. created an electrospun nanofiber mat using a
natural polymer SF added with l-ascorbic acid 2-phos-
phate, also known as vitamin C 2-phosphate (VC-2-p).
The unstable silk was transformed into water-stable
silk II after treatment with ethanol vapor. In vitro stud-
ies indicated ease of disassociation for VC-2-p from
the SF mat. The vitamin loaded and neat SF nanofiber
mats both showed good adhesion, spreading and pro-
liferation when tested with mouse fibroblast L929 cells.
However, the vitamin-loaded mat exhibited through a
real-time polymerase chain reaction enhanced expres-
sion of collagen-type I alpha 1. When nanofiber mats
were tested with an oxidative injury model, both mats
appeared to help in the antioxidation, but the vitamin-
loaded mat showed higher mRNA levels of collagen-
type I alpha 1 along with glutathione peroxidase 1 and
future science group
Electrospun polymer nanofibers for wound healing Review
catalase, both of which are vital-function genes. This
study shows how VC-2-p-loaded SF mats can help for
antiaging materials and enhance wound healing [3] .
Another important vitamin that has been reported
to accelerate the wound healing process is vitamin
E [4] . Vitamin E (VE) possesses anti-inflammatory
and antioxidant activities that reduce scaring [125] . In
a study by Sheng et al., vitamin E was fabricated with
SF creating electrospun nanofibrous mats. It was noted
that the amount of added vitamin E affected the mor-
phology of the fibers; at lower doses of incorporated
VE, a ribbon-like shape was produced while at higher
doses round fiber shapes were formed. Furthermore,
the addition of vitamin E enhanced the biological
properties. The drug release profile through an in vitro
study showed the sustained release of VE/SF. Mouse
skin cells proliferated much better on the VE/SF nano-
fibrous mats in comparison with the control culture.
Using VE in the mat increased the strength of the cells
against oxidation stress conditions [126] .
Growth factors
Growth factors are required in wound repair as they in
combination with low-molecular-weight compounds
achieve effective remodeling of epidermal and dermal
layers. Thus, of course, they have been incorporated
into wound dressing materials. Choi et al. reported
the addition of two growth factors, the endogenous
bFGF and an EGF, to a nanofiber dressing mat. The
bFGF causes an incline in the expression level of col-
lagen; hence, it acts as a vital player in proliferating
epidermal cells at the recovering epidermis [5] . The
EGF, on the other hand, acts on the keratinocytes by
means of increasing their proliferation and migration
by working along with growth factors. Using wound
dressing materials containing EGF increases the re-
epithelization rates of the wound cells and significantly
reduces the scarring [127] . The dressing incorporating
bFGF/EGF showed a strong influence on the wound
healing process and helped significantly in the re-epi-
thelization of the tissues of the wound. Application of
this dressing also influenced the accumulation of col-
lagen and keratin in the wound promoting the dressing
as a potential candidate for wound dressing material
that can minimize scar formation [5] .
Due to the usefulness of EGF in accelerating the
wound healing process, wound dressings containing
EGF can be utilized in specifically treating diabetic
ulcers, as their natural wound healing is not as efficient
as that in a nondiabetic patient. In such cases, wounds
may get to a chronic or more complicated stage, where
amputation is required. Proof of their wound process
acceleration has been studied as EGF was chemically
immobilized on the functional amine groups found
www.futuremedicine.com 10.2217/nnm.15.211
Review Hassiba, El Zowalaty, Nasrallah et al.
on the surface of biodegradable, poly(ethylene gly-
col)–poly(e-caprolactone)–poly(ethylene glycol) block
copolymer fibers. In vivo studies showed enhancement
of keratinocyte-specific genes, specifically those genes,
which accelerate the wound healing process [22,128] .
Metals & metal oxides
Different metals have been used as antibacterial agents
in fabricating electrospun wound dressing, and the
most common metal is silver [51,129–131] . Silver has bio-
cidal activity against a wide spectrum of bacteria and
relatively low bacterial resistance as compared with
other metal antimicrobial agents [132] . In wound heal-
ing, silver reduces inflammation and increases epithe-
lialization [133] . However, in order for silver to be used,
a reducing method must be followed while avoiding
possible cytotoxicity. Therefore, following an aqueous
route as a reducing method is better than an organic
agent [130] . Nguyen et al. blended PVA and silver
nanoparticles into electrospun fibers, and at the same
time used PVA as a reducing agent for silver nanoparti-
cles. After the electrospinning, the silver nanoparticles
were incorporated into the surface of the mat via heat
treatment as they are most effective on the surface.
This successful reducing method through PVA was
a faster and simpler process than other conventional
methods [131] .
The antibacterial activity of silver nanoparticles
was previously reported where silver nanoparticles
were electrospun with a PVA and chitosan blend
into a polymeric mat [51] . The fibers showed a strong
antibacterial inhibitory effect on E. coli and S. aureus
due to the silver nanoparticles. It also showed that
PVA/chitosan/silver nanoparticles ought to be more
effective than PVA/chitosan/silver nitrate as wound
dressing mats.
Titanium dioxide, an inorganic material also known
as titania, has been tested as a potential addition to
improve an electrospun wound dressing material. In
a study by Azad et al., titania in two forms, pure and
doped in iron, were electrospun with a ceramic/poly-
mer solution, and it showed antimicrobial behavior
against E. coli [134] . In another study, titania was incor-
porated into another electrospun polymeric mat, poly-
urethane nanofibers. The resulted fibers were tested
against S. aureus and Pseudomonas aeruginosa [135] .
Another study investigated the antibacterial activity of
titania after doping it with zinc. The results showed
the ability of electrospun PVA nanofibers contain-
ing titania doped with zinc to act against E. coli and
S. aureus [136] .
Zinc oxide nanoparticles were incorporated in a
nanofiber by Shalumon et al. using electrospinning.
Zinc oxide nanoparticles were integrated with PVA
10.2217/nnm.15.211 Nanomedicine (Lond.) (Epub ahead of print)
and sodium alginate hydrogel nanofibers. In vitro
studies showed that a small amount of zinc oxide
nanoparticles integrated into the mat had less toxic-
ity and better cell spreading in comparison to a larger
amount of the metal oxide nanoparticle. Antibacterial
studies of the later showed an excellent antibacterial
activity against S. aureus and E. coli. Figure 6 shows
the electron images by Bio-TEM of E. coli before and
after it is exposed to the nanofibers containing the zinc
oxide. The addition of zinc oxide to the nanofibrous
mat is expected to result in an improved wound dress-
ing, if the optimal zinc oxide nanoparticle concentra-
tion, with the least toxicity and most effectiveness, was
determined and used [137] . Table 2 summarizes the vari-
ous electrospun polymers developed for wound dress-
ing and their corresponding therapeutic agent loaded
on the nanofibrous mat.
Characterization of recently fabricated
wound dressing mats
Fourier transform infrared spectroscopy
Fourier transform infrared spectroscopy (FTIR) can
be used to identify the functional groups and con-
formational changes of samples. In a study done by
Khalil et al., PLGA nanofibers with silver nanopar-
ticles were fabricated and FTIR was carried out on
pure PLGA, PLGA nanofibers and PLGA with silver
nanoparticles. Three samples showed peaks between
1760 and 1050 cm-1 indicating the C=O and C–O
bonds, respectively, and bands at 3000 cm-1 that repre-
sent the alkyl groups. The results showed no significant
difference between the three samples [138] .
Thermogravimetric analysis
Unnithan et al. used thermogravimetric analysis to
study the heat resistance of PU-dextran nanofibers
with or without drugs. Tests were carried out on pris-
tine PU, PU-dextran blend and PU-dextran loaded
with the drug nanofiber. Pristine PU had the highest
heat resistance followed by PU-dextran loaded with
the drug and PU-dextran. This means that polymer
nanofiber blend was enhanced in terms of heat resis-
tance after the addition of the drug, which may be
due to the crystallinity of the drug molecule [139] .
Differential scanning calorimetry
Differential scanning calorimetry (DSC) is a ther-
mal analysis tool that can be used to study the glass
transition temperature, which is indication of flex-
ibility and crystallinity of fabricated nanofibers.
Sabitha et al. fabricated electrospun poly(e-cap-
rolactone urethane urea) (PEUU) in the presence
and absence of the antibacterial drug, tigecycline
(T-PEUU). DSC was used to identify glass transi-
future science group
 Electrospun polymer nanofibers for wound healing Review

1.0 µm 200 nm

100 nm 200 nm

Figure 6. Biotransmission electron microscope images. (A) Native Escherichia coli; (B) attachment of fabricated
nanofibers with the bacterial cell (red arrow and circle); (C) invasion of the bacterial cell by nanofibers (red
arrows) and (D) breakdown of Escherichia coli (red arrows).
Reproduced with permission from [136] © Springer (2011).

tion, crystallization and the melting temperatures of
the samples. PEUU showed a glass transition tem-
perature of -62°C while T-PEUU showed an increase
in the value to -51°C. This was explained by the
addition of tigecycline that acted as an antiplasti-
cizer. Furthermore, the N–H and C=O groups of
this drug interacted with similar groups found in the
PEUU fibers leading to the resultant increase in the
glass transition temperature. The melting tempera-
ture was also affected by the addition of tigecycline
because the value increased from of 53°C for PEUU
to 56°C for T-PEUU fibers [140] .
x-ray diffraction
Cheng et al. prepared wound dressing materi-
als using a chitosan (CS) and poly(ethylene oxide)
(PEO) blend loaded with two fluoroquinolone anti-
biotics, ciprofloxacin and moxifloxacin. x-ray dif-
fraction was carried out to quantitatively determine
the drug distribution in the polymeric mat. Intact
chitosan powder showed a peak at 2θ = 20.1 while
the blended polymers CS/PEO showed a peak at
2θ = 20.6 indicating the formation of a successful
polymeric blend. Intact ciprofloxacin powder showed
a different characteristic peaks at 2θ values of 19.04,
24.9, 26.6 and 29.4. After addition of 10% ciproflox-
acin to the CS/PEO blend, it had a peak at 2θ = 20.6.
Similarly, intact moxifloxacin powder had peaks at
2θ values of 19.4, 24.4, 27.5 and 29.6. After addition
of 10% moxifloxacin to the CS/PEO blend, a peak
was detected at 2θ = 20.6. This shows that amor-
phous distribution was achieved for both drugs in
the blend without affecting the characteristic crys-
tallinity of the polymeric nanofibers blend. CS/PEO
nanofibers were cross-linked using glutaraldehyde to
increase the tensile strength and improve the con-
trol of drug release of the dressing. Cross-linking of
CS/PEO shifted the peak at 2θ = 20.6 to 19.88 [141] .
In vitro drug release profile
Fu et al. used a coelectrospinning to develop a dress-
ing mat consisting of PCEC loaded with curcumin.

future science group www.futuremedicine.com 10.2217/nnm.15.211

Review Hassiba, El Zowalaty, Nasrallah et al.

Table 2. Therapeutic agent-loaded electrospun fibrous materials studied for wound dressing applications.
Electrospun polymers fibers Therapeutic agent Ref.
Silk fibroin/vitamin C 2-phosphate Vitamin C 2-phosphate [3]

Polycaprolactone/polyethylene glycol Basic fibroblast growth factor/epidermal growth factor [5]

Poly(vinyl alcohol)/poly(vinyl acetate) Ciprofloxacin [55]

Chitosan/polyethylene oxide/chitin nanocrystals Chitosan [89]

Silk fibroin/poly(lactide-co-glycolic acid) Silk fibroin [93]

Silk fibroin/polyethylenimine Silk fibroin [94]

Gelatin/poly(vinyl alcohol) Raspberry ketone [95]

Gelatin/poly(l-lactide) – [97]

Gelatin – [103]

Poly(vinyl alcohol)/chitosan – [104]

Poly(vinyl alcohol)/gum tragacanth – [111]

Poly(vinyl alcohol)/keratin – [113]

Poly(vinyl alcohol)/poly(vinyl pyrrolidone) – [114]

Poly(vinyl alcohol)/poly(vinyl pyrrolidone)/chitosan Chitosan

Poly(vinyl alcohol)/poly(vinyl pyrrolidone)-iodine Poly(vinyl pyrrolidone)-iodine
Poly(vinyl alcohol)/poly(acrylic acid) – [116]

Poly(vinyl alcohol)/poly(acrylic acid)/poly(vinyl pyrrolidone) –

Poly(vinyl alcohol)/poly(acrylic acid)/poly(vinyl pyrrolidone)- Poly(vinyl pyrrolidone)-iodine
iodine
Poly(vinyl alcohol)/poly(acrylic acid)/chitosan Chitosan
Poly(vinyl alcohol)/poly(vinyl pyrrolidone)-iodine/Poloxamer Poloxamer 188 [117]
188
Poly(vinyl alcohol)/poly(vinyl pyrrolidone)-iodine/chitosan Chitosan
Poly(vinyl alcohol)/polypropylene glycol – [121]

Poly(vinyl alcohol)/polyethylene glycol –

Silk fibroin/vitamin E Vitamin E [126]

poly(e-caprolactone)-poly(ethyleneglycol)-poly(e- EGF [22]

caprolactone)
Poly(vinyl alcohol) Silver nanoparticles [131]

Poly(vinyl alcohol)/chitosan Silver nanoparticles [51]

Polysulfone Polyethyleneimine-capped silver nanoparticles [129]

Polyurethane Silver nanoparticles [130]

Poly(vinyl pyrrolidone) Titanium dioxide [134]

Polyurethane Titania [135]

Poly(vinyl alcohol) Titania doped with zinc [136]

Poly(vinyl alcohol)/sodium alginate Zinc oxide [137]

Poly lactic-co-glycolic acid Silver nanoparticles [138]

Polyurethane-dextran Ciprofloxacin HCl [139]

Poly(e-caprolactone urethane urea) Tigecycline [140]

Chitosan/poly(ethylene oxide) Ciprofloxacin moxifloxacin [141]

poly(e-caprolactone) –poly(ethyleneglycol) –poly( e - Curcumin [142]

caprolactone)

10.2217/nnm.15.211 Nanomedicine (Lond.) (Epub ahead of print) future science group


Table 2. Therapeutic agent-loaded electrospun fibrous materials studied for wound dressing applications (cont.).
Electrospun polymers fibers
Polycaprolactone
poly(e-caprolactone)/polystyrene
Polycaprolactone/poly(lactic acid)
A drug release test was completed to investigate
the curcumin release behavior from the mat up to
10 days. Initial burst release was observed within
1 day, which might be due to drug present on the
surface of the mat. Thereafter, the recorded release
percentages were 52.7, 66.4, 78.5, and 87.2 for the
mats containing 5, 10, 15, and 20% of the drug,
respectively [142] .
Cell assays
Duman et al. conducted a cell proliferation test on
neat polycaprolactone (PCL) and PCL/collagen elec-
trospun nanofibers. Fibers were cultivated in 24-well
plates for 24 and 48 h and were tested using the
methylthiazolydipheyl-tetrazolium bromide (MMT)
method. This method depends on the cellular activ-
ity of viable cells to produce a colored solution mea-
sured colorimetrically. The results showed that both
neat PCL and PCL/collagen supported human kera-
tinocytes attachment and proliferation with no sig-
nificant difference in comparison with the positive
control [143] .
Motealleh et al. investigated a PCL/PS blend
as nanofibers containing chamomile as a drug. To
evaluate the in vitro cell proliferation, mesenchy-
mal cells were cultured on neat PCL/PS blend and
PCL/PS with chamomile. After 6 days of incuba-
tion, cell adhesion and morphology were studied
using FE-SEM. The drug-loaded fibers resulted in a
tenfold increase in cell proliferation than that of the
neat nanofibers [144] .
Wound closure & histological studies
In vivo studies are important tools to investigate the
healing rate and effect of dressing on wound tissues.
Karami et al. carried out these tests on PCL/PLA
fibers loaded with thymol. Male Wistar rats were
used and prepared by cutting 2 cm × 2 cm on their
backs and the wounds were covered by gauze (acts as
negative control), polymeric mat containing thymol
and a commercial wound dressing (acts as positive
control). Wounds were observed on days 1, 3, 7, 10
and 14, and the size of the wounds was recorded. His-
tological studies were completed on the tissue of the
injured area and stained using eosin and hematoxy-
lin. Wounds covered by gauze were not as effective
as other dressing. Due to the lack of moisture and
future science group
Electrospun polymer nanofibers for wound healing Review
Therapeutic agent Ref.
Collagen [143]
Chamomile [144]
Thymol [145]
dressing adhesion to the injured tissue, the removal
of the gauze led to damage to the underneath tissue.
Positive control samples were covered by commercial
wound dressing, which showed better cell growth
and fibroblast formation due to the relatively moist
area. Polymeric mats loaded with thymol showed an
enhanced wound healing performance, which might
have been due to the water vapor permeability, a fea-
ture missing in the positive control sample. On day
14 of the experiment, the recorded wound closure
percentage were 92.4, 87 and 68% for the polymeric
mat loaded with thymol, positive controls and nega-
tive controls, respectively [145] . Histological studies
at days 7 and 14 indicated that wounds covered with
negative controls showed severe inflammation and
necrosis while wound covered with positive controls
showed formation of fibroblast cells and blood ves-
sels, and collagen fibers. Furthermore, inflammation
and parts of the epidermis tissue were present due to
the use of a fabricated mat. After 14 days of treat-
ment, the negative control showed muscle degrada-
tion, the positive control showed similar results to
that of day 7, and the mat showed enhanced granula-
tion formation and tissue regeneration. In a nutshell,
the in vivo tests show that these fabricated mats pro-
vided enhanced wound healing in comparison to the
control groups [145] .
Conclusion
The present review provided insights into the recent
advances in wound dressing materials. It was shown
that nanofiber wound dressing materials displayed
advanced properties that can enhance wound repair
in comparison with other dressings. Of the meth-
ods used to fabricate nanofibers, electrospinning
is the most frequently chosen due to its simplicity,
cost–effectiveness and versatility. Electrospun nano-
fiber mats have morphologies of high surface area
to volume ratio and porous structure, which gives
it unique properties such as improved hemostasis,
exudate absorption, gas permeability and cell respi-
ration, thus better cell migration and proliferation.
This paper also discussed different evaluation tests
for the fabricated wound mats. Characterization tests
include: FTIR – to identify the functional groups and
conformational changes of samples; thermogravi-
metric analysis – to study heat resistance of nanofi-
www.futuremedicine.com 10.2217/nnm.15.211
Review Hassiba, El Zowalaty, Nasrallah et al.

bers; DSC – to study the glass transition temperature
as a measure of flexibility; and the crystallinities of
the fabricated nanofibers; x-ray diffraction – to study
the nanoparticles distribution such as silver nanopar-
ticles in the fibrous mat. Incorporation of antibiotics,
nonantibiotic antimicrobial agents (antiseptics) as
well as metal antimicrobial agents would improve the
antimicrobial properties of nanofibers for improved
antimicrobial properties of nanofibers to combat
microbial etiological agents for biomedical applica-
tions. A summary was also given of drug release and
biological assessments such as in vitro drug release
profile, cell proliferation and adhesion, histologi-
cal and wound closure studies that were conducted.
Therefore, the utilization of electrospinning to create
nanofibers can pave the way for the development of
new materials that will help obtain the ideal wound
dressing, which can be tailored for the type of wound
and the patient’s need for improved wound repair.
Future perspective
While this review has highlighted numerous
advances, which have been made in designing better
wound dressing materials, significantly more work
is still needed. If designed correctly, proper wound
dressings can effectively improve wound healing
ensuring a patient’s recovery without complications,
such as infection or chronic inflammation. In par-
ticular, better wound healing materials are needed to
simultaneously fight infection while improving tis-
sue healing, all without antibiotics for which bacteria
are developing a resistance toward. To combat this
problem, many researchers are currently conduct-
ing research studies using electrospinning to develop
biologically inspired nanofibrous polymeric wound
dressing mats comprised of two layers, which will
allow for dual functional mats where each layer has
a different function when applied on a wound. For
example, the upper layer of the mat facing the envi-
ronment may be loaded with antibacterial nanoparti-
cles to prevent environmental microorganisms from
entering the injured site. The lower side of the mat
facing the wound in turn can be loaded with factors
known to increase tissue regrowth. In addition, a mid-
dle layer could be added to reduce chronic inflamma-
tion. These types of composite materials can advance
the efficacy of wound healing dressing materials that
need to be the focus of future efforts. Moreover, there
are several developed techniques of electrospinning
that shall facilitate the development of such wound
dressing, such as coaxial electrospinning, for simul-
taneous electrospinning of two immiscible polymer
solutions producing a core–shell-shaped nanofibers
and tri-axial electrospinning that allows the creation
of trilayer-structured nanofibers.
Financial & competing interests disclosure
The authors thank Qatar University for supporting A El-
zatahry and A Hassiba under postgraduate student grant
number QUST-CAS-SPR-14\15–4. The authors have no
other relevant affiliations or financial involvement with any
organization or entity with a financial interest in or financial
conflict with the subject matter or materials discussed in the
manuscript apart from those disclosed.
No writing assistance was utilized in the production of this
manuscript.

Executive summary
Nanofibrous wound dressing mats
• There are several wound dressings that have been developed in the last century and continue to address
different needs for the patient’s recovery.
• Nanofibrous mats provides a wound dressing with a combination of unique properties due to the physical
feature of nanofibers (e.g., high surface area to volume ratio, high porosity and fibrous network mimicking
natural extracellular matrix).
Electrospun nanofibers mats
• There are several techniques by which nanofibers can be produced; however, electrospinning is immerging in
different applications, especially in the medical field, such as tissue engineering, drug delivery, wound healing
and biosensors, due to the simplicity, cost–effectiveness and versatility of the technique.
• Electrospun mats were shown to stimulate cell migration and proliferation, hemostasis, gas permeability,
exudate absorption and cell respiration.
• Fabricated nanofibers may be uploaded with growth factors, vitamins, antimicrobial agents and other
biologically active molecules known to encourage a healthy wound healing process.
• Table 2 summarizes the different electrospun polymers developed for wound dressing and the corresponding
therapeutic agent loaded on the mat.
Evaluation of electrospun nanofibers mats
• Numerous characterization tools can help in assessing the stability and functionality of the fabricated mat.
These methods will ensure the integrity of the fibers physically, chemically and biologically.

10.2217/nnm.15.211 Nanomedicine (Lond.) (Epub ahead of print) future science group


References
1 Abrigo M, McArthur SL, Kingshott P. Electrospun
nanofibers as dressings for chronic wound care: advances,
challenges, and future prospects. Macromol. Biosci. 14(6),
772–792 (2014).
2 Mogoşanu GD, Grumezescu AM. Natural and synthetic
polymers for wounds and burns dressing. Int. J. Pharm.
463(2), 127–136 (2014).
3 Fan L, Wang H, Zhang K et al. Vitamin C-reinforcing silk
fibroin nanofibrous matrices for skin care application. RSC
Adv. 2(10), 4110 (2012).
4 Zahedi P, Rezaeian I, Ranaei-Siadat SO, Jafari SH, Supaphol
P. A review on wound dressings with an emphasis on
electrospun nanofibrous polymeric bandages. Polym. Adv.
Technol. 21(2), 77–95 (2010).
5 Choi JS, Choi SH, Yoo HS. Coaxial electrospun nanofibers
for treatment of diabetic ulcers with binary release of
multiple growth factors. J. Mater. Chem. 21(14), 5258
(2011).
6 Kumbar SG, James R, Nukavarapu SP, Laurencin CT.
Electrospun nanofiber scaffolds: engineering soft tissues.
Biomed. Mater. 3(3), 034002 (2008).
7 Zhong SP, Zhang YZ, Lim CT. Tissue scaffolds for skin
wound healing and dermal reconstruction. Wiley Interdiscip.
Rev. Nanomed. Nanobiotechnol. 2(5), 510–525 (2010).
8 Mansbridge J. Skin tissue engineering. J. Biomater. Sci.
Polym. Ed. 19(8), 1–9 (2008).
9 Gaffal E, Cron M, Glodde N et al. Cannabis 1 receptors
in keratinocytes modulate proinflammatory chemokine
secretion and attenuate contact allergic inflammation.
J. Immunol. 190, 4929–4936 (2013).
10 Brisbois EJ, Handa H, Meyerhoff ME. Advanced Polymers in
Medicine. Springer, Switzerland (2015).
11 Iozzo R V. Basement membrane proteoglycans: from cellar
to ceiling. Nat. Rev. Mol. Cell Biol. 6(8), 646–656 (2005).
12 Ashcroft GS, Greenwell-Wild T, Horan MA, Wahl SM,
Ferguson MW. Topical estrogen accelerates cutaneous
wound healing in aged humans associated with an altered
inflammatory response. Am. J. Pathol. 155(4), 1137–1146
(1999).
13 Thornton MJ. The biological actions of estrogens on skin.
Exp. Dermatol. 11(6), 487–502 (2002).
14 Lazarus GS, Cooper DM, Knighton DR et al. Definitions
and guidelines for assessment of wounds and evaluation of
healing. Arch. Dermatol. 130(4), 489–493 (1994).
15 Hendrickson D, Virgin J. Factors that affect equine wound
repair. Vet. Clin. North Am. Equine Pract. 21(1), 33–44
(2005).
16 Ferreira MC, Tuma P, Carvalho VF, Kamamoto F. Complex
wounds. Clinics (Sao Paulo) 61(6), 571–578 (2006).
17 Moore K, McCallion R, Searle RJ, Stacey MC, Harding
KG. Prediction and monitoring the therapeutic response of
chronic dermal wounds. Int. Wound J. 3(2), 89–96 (2006).
18 Bhattarai N, Edmondson D, Veiseh O, Matsen FA, Zhang
M. Electrospun chitosan-based nanofibers and their cellular
compatibility. Biomaterials 26(31), 6176–6184 (2005).
future science group
Electrospun polymer nanofibers for wound healing Review
19 Strodtbeck F. Physiology of wound healing. Newborn Infant
Nurs. Rev. 1(1), 43–52 (2001).
20 Shakespeare P. Burn wound healing and skin substitutes.
Burns 27, 517–522 (2001).
21 Boateng JS, Matthews KH, Stevens HNE, Eccleston GM.
Wound healing dressings and drug delivery systems: a review.
J. Pharm. Sci. 97(8), 2892–2923 (2008).
22 Rieger KA, Birch NP, Schiffman JD. Designing electrospun
nanofiber mats to promote wound healing – a review.
J. Mater. Chem. B 1, 4531 (2013).
23 Baum CL, Arpey CJ. Normal cutaneous wound healing:
clinical correlation with cellular and molecular events.
Dermatol. Surg. 31(6), 674–686 (2005).
24 Shai A, Maibach HI. Wound healing and ulcers of the skin:
diagnosis and therapy - the practical approach. Practical
Diabetes International 22(8), 283 (2005).
25 Wilgus TA. Immune cells in the healing skin wound:
influential players at each stage of repair. Pharmacol. Res.
58(2), 112–116 (2008).
26 Diegelmann RF, Evans MC. Wound healing: an overview
of acute, fibrotic and delayed healing. Front. Biosci. 9(4),
283–289 (2004).
27 Jayakumar R, Prabaharan M, Sudheesh Kumar PT, Nair
SV, Tamura H. Biomaterials based on chitin and chitosan in
wound dressing applications. Biotechnol. Adv. 29(3), 322–337
(2011).
28 Daunton C, Kothari S, Smith L, Steele D. A history of
materials and practices for wound management. Wound
Practice & Research 20(4), 174 (2012).
29 Jones VJ. The use of gauze: will it ever change? Int. Wound
J. 3(2), 79–86 (2006).
30 Eaglstein WH. Moist wound healing with occlusive dressings:
a clinical focus. Dermatologic. Surg. 27, 175–181 (2001).
31 Winter GD. Formation of the scab and the rate of
epithelisation of superficial wounds in the skin of the young
domestic pig. Nature 193(4812), 293–294 (1962).
32 Macaya D, Spector M. Injectable hydrogel materials for spinal
cord regeneration: a review. Biomed. Mater. 7(1), 012001
(2012).
33 Biazar E, Roveimiab Z, Shahhosseini G, Khataminezhad
M, Zafari M, Majdi A. Biocompatibility evaluation of a new
hydrogel dressing based on polyvinylpyrrolidone/polyethylene
glycol. J. Biomed. Biotechnol. 2012, 343989 (2012).
34 Juris S. Biodegradable polysaccharide gels for skin scaffolds.
J. Biomater. Nanobiotechnol. 2(3), 216–225 (2011).
35 Dinah F, Adhikari A. Gauze packing of open surgical
wounds: empirical or evidence-based practice? Ann. R. Coll.
Surg. Engl. 88(1), 33–36 (2006).
36 Jones V, Grey JE, Harding KG. Wound dressings. BMJ
332, 777–780 (2006).
37 Martineau L, Shek PN. Evaluation of a bi-layer wound
dressing for burn care I. Cooling and wound healing
properties. Burns 32(1), 70–76 (2006).
38 Dumville JC, Deshpande S, O’Meara S, Speak K. Foam
dressings for healing diabetic foot ulcers (review). Cochrane
Database Syst. Rev. (9), CD009111 (2011).
www.futuremedicine.com 10.2217/nnm.15.211
Review Hassiba, El Zowalaty, Nasrallah et al.
39 Vowden K, Vowden P. Wound dressings: principles and
practice. Surgery 32(9), 462–467 (2014).
40 Blaine MG. Experimental observations on absorbable. Ann.
Surg. 125, 102–114 (1946).
41 Weller C, Sussman G. Wound dressings update. J. Pharm.
Pract. Res. 36(4), 39–42 (2006).
42 Gilchrist T, Martin a M. Wound treatment with sorbsan –
an alginate fibre dressing. Biomaterials 4, 317–320 (1983).
43 Dumville JC, O’Meara S, Deshpande S, Speak K. Hydrogel
dressings for healing diabetic foot ulcers (review). Cochrane
Database Syst. Rev. 9(7), 1–48 (2013).
44 Thomas S, Loveless P. A comparative study of the properties
of twelve hydrocolloid dressings. World Wide Wounds 1997,
1–10 (1997).
45 Angel D, Morey P, Storer J, Mwipatayi B. The great
debate over iodine in wound care continues: a review of
the literature. Wound Pract. Res. J. Aust. Wound Manag.
Assoc. 16(1), 6–21 (2008).
46 Sibbald R, Leaper D, Queen D. Iodine made easy. Wounds
Int. 2(2), 1–6 (2011).
47 Cooper RA. Iodine revisited. Int. Wound J. 4 (2), 124–137
(2007).
48 Wei L, Tang J, Zhang Z, Chen Y, Zhou G, Xi T.
Investigation of the cytotoxicity mechanism of silver
nanoparticles in vitro. Biomed. Mater. 5(4), 044103 (2010).
49 Poon VKM, Burd A. In vitro cytotoxity of silver:
implication for clinical wound care. Burns 30(2), 140–147
(2004).
50 Leaper DJ. Silver dressings: their role in wound
management. Int. Wound J. 3(4), 282–294 (2006).
51 Li CW, Fu RQ, Yu CP et al. Silver nanoparticle/chitosan
oligosaccharide/poly(vinyl alcohol) nanofibers as wound
dressings: a preclinical study. Int. J. Nanomed. 8, 4131–4145
(2013).
52 Zhang Y, Lim CT, Ramakrishna S, Huang Z-M. Recent
development of polymer nanofibers for biomedical and
biotechnological applications. J. Mater. Sci. Mater. Med.
16(10), 933–946 (2005).
53 Gholipour Kanani A, Hajir Bahrami S. Review on
electrospun nanofibres scaffold and biomedical applications.
Trends Biomater. Artif. Organs 24(2), 93–115 (2010).
54 Martindale D. Scar no more. Sci. Am. 283, 34–36 (2000).
55 Jannesari M, Varshosaz J, Morshed M, Zamani M.
Composite poly(vinyl alcohol)/poly(vinyl acetate)
electrospun nanofibrous mats as a novel wound dressing
matrix for controlled release of drugs. Int. J. Nanomed.
6, 993–1003 (2011).
56 Dicks LMT, Heunis TDJ. Nanofibers offer alternative
ways to the treatment of skin infections. J. Biomed.
Biotechnol. 2010, pii: 510682 (2010).
57 Nayak R, Padhye R, Kyratzis IL, Truong YB, Arnold L.
Recent advances in nanofibre fabrication techniques. Text
Res. J. 82(2), 129–147 (2012).
58 Hartgerink JD, Beniash E, Stupp SI. Self-assembly
and mineralization of peptide-amphiphile nanofibers.
Science 294(5547), 1684–1688 (2001).
10.2217/nnm.15.211 Nanomedicine (Lond.) (Epub ahead of print)
59 Luo C, Stoyanov S, Stride E, Pelan E, Edirisinghe M.
Electrospinning versus fibre production methods: from
specifics to technological convergence. Chem. Soc. Rev.
41(13), 4708–4735 (2012).
60 Khan N. Applications of electrospun nanofibers in the
biomedical field. SURG 5(2), 63–73 (2012).
61 Kanani a. G, Bahrami SH. Review on electrospun nanofibres
scaffold and biomedical applications. Trends Biomater. Artif.
Organs 24(2), 93–115 (2010).
62 Haghi AK, Akbari M. Trends in electrospinning of natural
nanofibers. Physica Status Solidi A. Appl. Res. 204(6),
1830–1834 (2007).
63 Sukigara S, Gandhi M, Ayutsede J, Micklus M, Ko F.
Regeneration of Bombyx mori silk by electrospinning–part 1:
processing parameters and geometric properties. Polymer
(Guildf.) 44(19), 5721–5727 (2003).
64 Tan EPS, Ng SY, Lim CT. Tensile testing of a single ultrafine
polymeric fiber. Biomaterials 26(13), 1453–1456 (2005).
65 Pillay V, Dott C, Choonara YE et al. A review of the effect
of processing variables on the fabrication of electrospun
nanofibers for drug delivery applications. J. Nanomater. 2013,
789289 (2013).
66 Bhardwaj N, Kundu SC. Electrospinning: a fascinating
fiber fabrication technique. Biotechnol. Adv. 28(3), 325–347
(2010).
67 Pham QP, Sharma U, Mikos AG. Electrospun poly(epsilon-
caprolactone) microfiber and multilayer nanofiber/microfiber
scaffolds: characterization of scaffolds and measurement of
cellular infiltration. Biomacromolecules 7(10), 2796–2805
(2006).
68 Zhang C, Yuan X, Wu L, Han Y, Sheng J. Study on
morphology of electrospun poly(vinyl alcohol) mats. Eur.
Polym. J. 41(3), 423–432 (2005).
69 Ki CS, Baek DH, Gang KD, Lee KH, Um IC, Park YH.
Characterization of gelatin nanofiber prepared from gelatin-
formic acid solution. Polymer (Guildf.) 46(14), 5094–5102
(2005).
70 Geng X, Kwon OH, Jang J. Electrospinning of
chitosan dissolved in concentrated acetic acid solution.
Biomaterials 26(27), 5427–5432 (2005).
71 Zhao Z, Li J, Yuan X, Li X, Zhang Y, Sheng J. Preparation
and properties of electrospun poly(vinylidene fluoride)
membranes. J. Appl. Polym. Sci. 97(2), 466–474 (2005).
72 Yuan XY, Zhang YY, Dong C, Sheng J. Morphology of
ultrafine polysulfone fibers prepared by electrospinning.
Polym. Int. 53(11), 1704–1710 (2004).
73 Kim KH, Jeong L, Park HN et al. Biological efficacy of silk
fibroin nanofiber membranes for guided bone regeneration.
J. Biotechnol. 120(3), 327–339 (2005).
74 Wannatong L, Sirivat A, Supaphol P. Effects of solvents
on electrospun polymeric fibers: preliminary study on
polystyrene. Polym. Int. 53(11), 1851–1859 (2004).
75 Sundaray B, Subramanian V, Natarajan TS, Xiang RZ,
Chang CC, Fann WS. Electrospinning of continuous aligned
polymer fibers. Appl. Phys. Lett. 84(7), 1222–1224 (2004).
76 Li D, Xia Y. Electrospinning of nanofibers: reinventing the
wheel? Adv. Mater. 16(14), 1151–1170 (2004).
future science group

77 Xu CY, Inai R, Kotaki M, Ramakrishna S. Aligned
biodegradable nanofibrous structure: a potential scaffold
for blood vessel engineering. Biomaterials 25(5), 877–886
(2004).
78 Wang X, Um IC, Fang D, Okamoto A, Hsiao BS, Chu B.
Formation of water-resistant hyaluronic acid nanofibers
by blowing-assisted electro-spinning and non-toxic post
treatments. Polymer (Guildf.) 46(13), 4853–4867 (2005).
79 Reneker DH, Chun I. Nanometre diameter fibres of polymer,
produced by electrospinning. Nanotechnology 7(3), 216–223
(1999).
80 Supaphol P, Mit-Uppatham C, Nithitanakul M. Ultrafine
electrospun polyamide-6 fibers: effect of emitting electrode
polarity on morphology and average fiber diameter. J. Polym.
Sci. B Polym. Phys. 43(24), 3699–3712 (2005).
81 Casper CL, Stephens JS, Tassi NG, Chase DB, Rabolt JF.
Controlling surface morphology of electrospun polystyrene
fibers: effect of humidity and molecular weight in the
electrospinning process. Macromolecules 37(2), 573–578
(2004).
82 Yu D-G, White K, Chatterton N, Li Y, Li L, Wang
X. Structural lipid nanoparticles self-assembled from
electrospun core–shell polymeric nanocomposites. RSC
Adv. 5(13), 9462–9466 (2015).
83 Yu D-G, Li X-Y, Wang X, Yang J-H, Bligh SWA, Williams
GR. Nanofibers fabricated using triaxial electrospinning
as zero order drug delivery systems. ACS Appl. Mater.
Interfaces 7(33), 18891–18897 (2015).
84 Cook N. Methicillin-resistant Staphylococcus aureus versus
the burn patient. Burns 24(2), 91–98 (1998).
85 Chen G, Xu Y, Yu D-G, Zhang D-F, Chatterton NP,
White KN. Structure-tunable Janus fibers fabricated using
spinnerets with varying port angles. Chem. Commun. 51(22),
4623–4626 (2015).
86 Li L, Hsieh Y Lo. Chitosan bicomponent nanofibers and
nanoporous fibers. Carbohydr. Res. 341(3), 374–381 (2006).
87 Pakravan M, Heuzey MC, Ajji A. A fundamental study of
chitosan/PEO electrospinning. Polymer (Guildf.) 52(21),
4813–4824 (2011).
88 Charernsriwilaiwat N, Rojanarata T, Ngawhirunpat T,
Opanasopit P. Electrospun chitosan/polyvinyl alcohol
nanofibre mats for wound healing. Int. Wound J. 11(2),
215–222 (2014).
89 Naseri N, Algan C, Jacobs V, John M, Oksman K, Mathew
AP. Electrospun chitosan-based nanocomposite mats
reinforced with chitin nanocrystals for wound dressing.
Carbohydr. Polym. 109, 7–15 (2014).
90 Ki CS, Park YH, Jin H-J. Silk protein as a fascinating
biomedical polymer: structural fundamentals and
applications. Macromol. Res. 17(12), 935–942 (2009).
91 Padamwar MN, Pawar AP. Silk sericin and its applications: a
review. J. Sci. Ind. Res. (India) 63(4), 323–329 (2004).
92 Vasconcelos A, Freddi G, Cavaco-Paulo A. Biodegradable
materials based on silk fibroin and keratin. Biomacromolecules
9(4), 1299–1305 (2008).
93 Shahverdi S, Hajimiri M, Esfandiari MA et al. Fabrication
and structure analysis of poly(lactide-co-glycolic acid)/silk
future science group
Electrospun polymer nanofibers for wound healing Review
fibroin hybrid scaffold for wound dressing applications. Int.
J. Pharm. 473(1–2), 345–355 (2014).
94 Çalamak S, Erdoğdu C, Özalp M, Ulubayram K. Silk fibroin
based antibacterial bionanotextiles as wound dressing
materials. Mater. Sci. Eng. C. 43, 11–20 (2014).
95 Yang D, Li Y, Nie J. Preparation of gelatin/PVA nanofibers
and their potential application in controlled release of drugs.
Carbohydr. Polym. 69(3), 538–543 (2007).
96 Ulubayram K, Aksu E, Gurhan SID, Serbetci K, Hasirci
N. Cytotoxicity evaluation of gelatin sponges prepared
with different cross-linking agents. J. Biomater. Sci. Polym.
Ed. 13(11), 1203–1219 (2002).
97 Gu SY, Wang ZM, Ren J, Zhang CY. Electrospinning
of gelatin and gelatin/poly(l-lactide) blend and its
characteristics for wound dressing. Mater. Sci. Eng. C. 29(6),
1822–1828 (2009).
98 Ki CS, Baek DH, Gang KD, Lee KH, Um IC, Park YH.
Characterization of gelatin nanofiber prepared from gelatin–
formic acid solution. Polymer (Guildf.) 46(14), 5094–5102
(2005).
99 Huang Z-M, Zhang Y, Ramakrishna S, Lim C.
Electrospinning and mechanical characterization of gelatin
nanofibers. Polymer (Guildf.) 45(15), 5361–5368 (2004).
100 Songchotikunpan P, Tattiyakul J, Supaphol P. Extraction
and electrospinning of gelatin from fish skin. Int. J. Biol.
Macromol. 42(3), 247–255 (2008).
101 Zhang YZ, Venugopal J, Huang ZM, Lim CT, Ramakrishna
S. Crosslinking of the electrospun gelatin nanofibers. Polymer
(Guildf.) 47:2911–2917 (2006).
102 Li M, Mondrinos MJ, Gandhi MR, Ko FK, Weiss AS,
Lelkes PI. Electrospun protein fibers as matrices for tissue
engineering. Biomaterials 26(30), 5999–6008 (2005).
103 Lu W, Ma M, Xu H, Zhang B, Cao X, Guo Y. Gelatin nano
fibers prepared by spiral-electrospinning and cross-linked by
vapor and liquid-phase glutaraldehyde. Mater. Lett. 140, 1–4
(2015).
104 Kang YO, Yoon IS, Lee SY et al. Chitosan-coated poly(vinyl
alcohol) nanofibers for wound dressings. J. Biomed. Mater.
Res. B Appl. Biomater. 92(2), 568–576 (2010).
105 Li X, Kanjwal MA, Lin L, Chronakis IS. Electrospun
polyvinyl-alcohol nanofibers as oral fast-dissolving
delivery system of caffeine and riboflavin. Colloids Surf. B
Biointerfaces 103, 182–188 (2013).
106 Kadri NA, Raha MG, Pingguan-Murphy B. Polyvinyl
alcohol as a viable membrane in artificial tissue design and
development. Clinics (Sao Paulo) 66(8), 1489–1494 (2011).
107 Kamoun EA, Chen X, Mohy Eldin MS, Kenawy ERS.
Crosslinked poly(vinyl alcohol) hydrogels for wound dressing
applications: a review of remarkably blended polymers.
Arabian J. Chem. 8(1), 1–14 (2014).
108 O’ Mahony J, O’ Donoghue M, Morgan JG, Hill C.
Rotavirus survival and stability in foods as determined
by an optimised plaque assay procedure. Int. J. Food
Microbiol. 61(2–3), 177–185 (2000).
109 Moghbel A, Agheli H, Kalantari E, Naji M. Design and
formulation of tragacanth dressing bandage for burn healing
with no dermal toxicity. Toxicol. Lett. 180, S154 (2008).
www.futuremedicine.com 10.2217/nnm.15.211
Review Hassiba, El Zowalaty, Nasrallah et al.
110 Siahi MR, Barzegar-Jalali M, Monajjemzadeh F, Ghaffari F,
Azarmi S. Design and evaluation of 1- and 3-layer matrices
of verapamil hydrochloride for sustaining its release. AAPS
Pharm. Sci. Tech. 6(4), E626–E632 (2005).
111 Ranjbar-Mohammadi M, Bahrami SH, Joghataei MT.
Fabrication of novel nanofiber scaffolds from gum
tragacanth/poly(vinyl alcohol) for wound dressing
application: in vitro evaluation and antibacterial properties.
Mater. Sci. Eng. C. 33(8), 4935–4943 (2013).
112 Rouse JG, Van Dyke ME. A review of keratin-based
biomaterials for biomedical applications. Materials
(Basel) 3(2), 999–1014 (2010).
113 Park M, Shin HK, Panthi G et al. Novel preparation and
characterization of human hair-based nanofibers using
electrospinning process. Int. J. Biol. Macromol. 76, 45–48
(2015).
114 Gökmeşe F, Uslu İ, Aytimur A. Preparation and
characterization of PVA/PVP nanofibers as promising
materials for wound dressing. Polym. Plast. Technol.
Eng. 52(12), 1259–1265 (2013).
115 McDonnell G, Russelll D. Antiseptics and disinfectants:
activity, action, and resistance. Am. Soc. Microbiol. 12(1),
147–179 (1999).
116 Aytimur A, Uslu İ. Promising materials for wound dressing:
PVA/PAA/PVP electrospun nanofibers. Polym. Plast.
Technol. Eng. 53(7), 655–660 (2014).
117 Aytimur A, Koçyiğit S, Uslu İ. Synthesis and characterization
of poly(vinyl alcohol)/poly(vinyl pyrrolidone)-iodine
nanofibers with poloxamer 188 and chitosan. Polym. Plast.
Technol. Eng. 52(7), 661–666 (2013).
118 Lee RC, River LP, Pan FS, Ji L, Wollmann RL. Surfactant-
induced sealing of electropermeabilized skeletal muscle
membranes in vivo. Proc. Natl Acad. Sci. USA 89(10),
4524–4528 (1992).
119 Abdelaal MY, Makki MSI, Sobahi TRA. Modification and
characterization of polyacrylic acid for metal ion recovery.
Am. J. Polym. Sci. 2(4), 73–78 (2012).
120 Pinto MCC, Gomes FW, Melo CK, Melo PA, Castro M,
Pinto JC. Production of poly(acrylic acid) particles dispersed
in organic media. Macromol. Symp. 319(1), 15–22 (2012).
121 Aytimur A, Koçyiğit S, Uslu İ, Gökmeşe F. Preparation
and characterization of polyvinyl alcohol based copolymers
as wound dressing fibers. Int. J. Polym. Mater. Polym.
Biomater. 64(3), 111–116 (2014).
122 Tsou TL, Tang ST, Huang YC, Wu JR, Young JJ, Wang
HJ. Poly(2-hydroxyethyl methacrylate) wound dressing
containing ciprofloxacin and its drug release studies.
J. Mater. Sci. Mater. Med. 16(2), 95–100 (2005).
123 Hartwell R, Leung V, Chavez-Munoz C et al. A novel
hydrogel-collagen composite improves functionality of
an injectable extracellular matrix. Acta Biomater. 7(8),
3060–3069 (2011).
124 Sill TJ, von Recum HA. Electrospinning: applications in
drug delivery and tissue engineering. Biomaterials 29(13),
1989–2006 (2008).
125 Jiang Q. Natural forms of vitamin E: metabolism,
antioxidant, and anti-inflammatory activities and their role
10.2217/nnm.15.211 Nanomedicine (Lond.) (Epub ahead of print)
in disease prevention and therapy. Free Radic. Biol. Med. 72,
76–90 (2014).
126 Sheng X, Fan L, He C, Zhang K, Mo X, Wang H. Vitamin
E-loaded silk fibroin nanofibrous mats fabricated by green
process for skin care application. Int. J. Biol. Macromol. 56,
49–56 (2013).
127 Ulubayram K, Cakar AN, Korkusuz P, Ertan C, Hasirci
N. EGF containing gelatin-based wound dressings.
Biomaterials 22(11), 1345–1356 (2001).
128 Choi JS, Leong KW, Yoo HS. In vivo wound healing
of diabetic ulcers using electrospun nanofibers
immobilized with human epidermal growth factor (EGF).
Biomaterials 29(5), 587–596 (2008).
129 Schiffman JD, Wang Y, Giannelis EP, Elimelech M.
Biocidal activity of plasma modified electrospun polysulfone
mats functionalized with polyethyleneimine-capped silver
nanoparticles. Langmuir 27(21), 13159–13164 (2011).
130 Lakshman L, Shalumon KT, Nair S, Jayakumar R, Nair SV.
Preparation of silver nanoparticles incorporated electrospun
polyurethane nano-fibrous mat for wound dressing.
J. Macromol. Sci. A 47(10), 1012–1018 (2010).
131 Nguyen TH, Kim YH, Song HY, Lee BT. Nano Ag loaded
PVA nano-fibrous mats for skin applications. J. Biomed.
Mater. Res. B Appl. Biomater. 96B(2), 225–233 (2011).
132 Wilkinson LJ, White RJ, Chipman JK. Silver and
nanoparticles of silver in wound dressings: a review of
efficacy and safety. J. Wound Care 20(11), 543–549 (2011).
133 Wong KKY, Cheung SOF, Huang L et al. Further evidence
of the anti-inflammatory effects of silver nanoparticles. Chem
Med Chem 4(7), 1129–1135 (2009).
134 Azad A-M, Hershey R, Ali S, Goel V. Bactericidal efficacy of
electrospun pure and Fe-doped titania nanofibers. J. Mater.
Res. 25(09), 1761–1770 (2010).
135 Yan L, Si S, Chen Y et al. Electrospun in-situ hybrid
polyurethane/nano-TiO2 as wound dressings. Fibers
Polym. 12(2), 207–213 (2011).
136 Amna T, Hassan MS, Barakat NAM et al. Antibacterial
activity and interaction mechanism of electrospun zinc-
doped titania nanofibers. Appl. Microbiol. Biotechnol. 93(2),
743–751 (2012).
137 Shalumon KT, Anulekha KH, Nair SV, Nair SV, Chennazhi
KP, Jayakumar R. Sodium alginate/poly(vinyl alcohol)/nano
ZnO composite nanofibers for antibacterial wound dressings.
Int. J. Biol. Macromol. 49(3), 247–254 (2011).
138 Khalil KA, Fouad H, Elsarnagawy T, Almajhdi FN.
Preparation and characterization of electrospun PLGA/silver
composite nanofibers for biomedical applications. Int.
J. Electrochem. Sci. 8, 3483–3493 (2013).
139 Unnithan AR, Barakat NAM, Tirupathi Pichiah PB et al.
Wound-dressing materials with antibacterial activity from
electrospun polyurethane–dextran nanofiber mats containing
ciprofloxacin HCl. Carbohydr. Polym. 90(4), 1786–1793
(2012).
140 Sabitha M, Rajiv S. Synthesis and characterization of
biocompatible tigecycline imbibed electrospun poly e-
caprolactone urethane urea fibers. RSC Adv. 5(3), 2249–2257
(2015).
future science group

141 Cheng F, Gao J, Wang L, Hu X. Composite chitosan/
poly(ethylene oxide) electrospun nanofibrous mats as novel
wound dressing matrixes for the controlled release of drugs.
J. Appl. Polym. Sci. 132(24), 42060 (2015).
142 Fu S-Z, Meng X-H, Fan J et al. Acceleration of dermal
wound healing by using electrospun curcumin-loaded
poly(e-caprolactone)-poly(ethylene glycol)-poly(e-
caprolactone) fibrous mats. J. Biomed. Mater. Res. B Appl.
Biomater. 102(3), 533–542 (2014).
143 Duman M, Şendemir Ürkmez A, Zeybek B. Electrospinning
of nanofibrous polycaprolactone (PCL) and collagen-blended
polycaprolactone for wound dressing and tissue engineering.
Usak. Univ. J. Mater. Sci. 3(1), 121–121 (2014).
future science group
Electrospun polymer nanofibers for wound healing Review
144 Motealleh B, Zahedi P, Rezaeian I, Moghimi M,
Abdolghaffari AH, Zarandi MA. Morphology, drug
release, antibacterial, cell proliferation, and histology
studies of chamomile-loaded wound dressing mats based on
electrospun nanofibrous poly(e-caprolactone)/polystyrene
blends. J. Biomed. Mater. Res. B Appl. Biomater. 102(5),
977–987 (2014).
145 Karami Z, Rezaeian I, Zahedi P, Abdollahi M. Preparation
and performance evaluations of electrospun poly(e-
caprolactone), poly(lactic acid), and their hybrid (50/50)
nanofibrous mats containing thymol as an herbal drug
for effective wound healing. J. Appl. Polym. Sci. 129(2),
756–766 (2013).
www.futuremedicine.com 10.2217/nnm.15.211