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bio medical applications of nano fibers



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University of Babylon
College of Material Engineering
Polymer & Petrochemical Industry Department
Post graduate
First Class
Seminar Title:
Biomedical Applications of Nano Fibers
Science and Technology of Polymer Nano fiber
Anthony L. Andrady
Dr. Zuhair
Presented by
Sura Falah sabri
1-1 Introduction
Nanofibers are exciting new class of material used for several value
added applications such as medical, filtration , composite, insulation, and
Low density, large surface area to mass, high pore . energy storage
are the characteristics of the nanofibers. volume, and tight pore size
Nanofibers exhibits special properties mainly due to extremely high
surface to weight ratio compared to conventional fibers. Two
particularly promising biomedical research areas are focused on
Nanofiber-based three dimensional scaffolds for tissue engineering and
fiber devices for controlled delivery of Nanothe design of
fiber mats in scaffolding The success of polymer Nano pharmaceuticals.
applications is primarily because their size range closely matches the
t.environmenfeatures present in body tissue structural
Fig. 1.1 Nanofibers
Methods for nanofiber synthesis
Currently, there are three techniques available for the synthesis of
. Of assembly, and phase separation-spinning, selfelectronanofibers:
spinning is the most widely studied technique and also electrothese,
seems to exhibit the most promising results for tissue engineering
assembly and phase -applications. Nanofibers synthesized by self
separation have had relatively limited studies that explored their
lication as scaffolds for tissue
epresents an attractive technique for the processing of polymeric R
This technique also offers the opportunity biomaterials into nanofibers.
for control over thickness and composition of the nanofibers along with
tively simple experimental using a rela porosity of the nanofiber meshes
spraying has -Although the concept of electrospinning or electro ,setup
The high surface area and high known for more than a century, been
porosity of electrospun nanofibers allow favorable cell interactions and
. hence make them potential candidates for tissue engineering applications
ranging from 50 nm to 1000 nm or In the electrospinning process, fibers
can be produced by applying an electric potential to a polymeric tergrea
The solution is held at the tip of a capillary tube by virtue of its solution
charge to the surface tension. The electrical potential applied provides a
pulsion in the polymer solution Mutual charge repolymer solution.
induces a force that is directly opposite to the surface tension of the
An increase in the electrical potential initially leads to polymer solution.
the elongation of the hemispherical surface of the solution at the tip of
a ,the capillary tube to form a conical shape known as the Taylor cone
further increase causes the electric potential to reach a critical value, at
which it overcomes the surface tension forces to cause the formation of a
f the Taylor cone. The charged jet jet that is ejected from the tip o
undergoes instabilities and gradually thins in air primarily due to
The charged jet eventually forms ,elongation and solvent evaporation
randomly oriented nanofibers that can be collected on a stationary or
.grounded metallic collectorrotating
FIG. 1.2
Self-assembly involves the spontaneous organization of individual
components into an ordered and stable structure with preprogrammed
non-covalent bonds. Self-assembly, that is, the autonomous organization
of molecules into patterns or structures without human intervention. Self-
assembly of natural or synthetic macromolecules produces nanoscaled
supramolecular structures, sometimes nanofibers. Compared with
electrospinning, self-assembly can produce much thinner nanofibers only
several nanometers in diameter, but requires much more complicated
procedures and extremely elaborate techniques. The low productivity of
the self-assembly method is another limitation.
Fig. 1.3
Phase separation
Phase separation is a method frequently used to prepare 3-D tissue
engineering scaffolds. Phase separation is a thermodynamic separation of
a polymer solution into a polymer-rich component and a polymer-
poor/solvent-rich component. Essentially, a polymer is dissolved in
solution and the phase separation is induced, either thermally (most
common method) or through the addition of a non-solvent to the polymer
solution to create a gel. Water is then used to extract the solvent from the
gel; the gel is cooled to a temperature below the glass transition
temperature of the polymer and freeze dried under vacuum to produce a
nanofibrous scaffold. Polymer scaffolds obtained by the phase separation
method usually have a sponge like porous morphology with microscale
spherical pores . Unlike self-assembly, phase separation is a simple
technique that does not require much specialized equipment. It is also
easy to achieve batch-to-batch consistency, and tailoring of scaffold
mechanical properties and architecture is easily achieved by varying
polymer/porogen (sugar, inorganic salt, paraffin spheres) concentrations.
However, this method is limited to being effective with only a select
number of polymers and is strictly a laboratory scale technique.
Fig. 1.4
1.To optimize drugs therapeutic effect, convenience and dose.
2.To improve patient compliance.
3.To target drug delivery.
4.To control overall healthcare costs.
5.To facilitate biological drug delivery.
6.minimizes potential side effects.
1-2 Drug Delivery Applications
Conventional delivery of a drug in successive doses results in a blood (
or other tissue phases ) concentration profile of the drug that fluctuates
over the duration of therapy. Therefore, over significant duration, the
, with
ended maximum value Cconcentrations may exceed the recomm
, or fall below the minimum effective bio toxicitythe rick of
To drive the highest ., limiting the therapeutic effect
concentration , C
) should
<C < C
therapeutic value, an optimum concentration C (C
be maintained in the body tissue over the full duration of treatment.
The objective of drug delivery systems is to deliver a defined amount of
drug efficiently, precisely and for defined period of time. Drug delivery
with polymer nanofibers is based on principle that dissolution rate of a
drug particulate increases with increased surface area of both the drug
and the corresponding carrier. controlled delivery systems are used to
improve the therapeutic efficiency and safety of drug by delivering them
to the site of action at a rate dictated by the need of the physiological
A variety of polymeric materials have been used as delivery matrices,
and the choice of the delivery vehicle polymer is determined by the
requirements of the specific application. Polymeric nanofibers have
recently been explored for their ability to encapsulate and deliver
bioactive molecules for therapeutic applications.
The simplest configuration of a controlled release device is where a drug
is either dissolved in high concentration or suspended as
particles in a monolithic polymer such as a cylindrical polymer fiber. The
release of the drug from it may occur via :
1-Diffusive transfer through the polymer matrix to the surrounding
tissue .
2-Release of the dissolved or suspended drug due to slow biodegradation
or erosion of the surface layers of the fiber.
3-Rapid delivery of the drug due to dissolution of the fiber.
4-Slow release of covalently bonded drug via hydrolytic cleavage of the
1-3 Drug-Loaded Nanofibers
The kinetics of release of the drug is controlled by the semicrystaline
nature of the polymer as well as by the morphology of the polymer / drug
composite. Three basic morphological models for drug loaded nan-fiber
polymers are :
A-Drug dissolved in polymer matrix at the molecular level.
B-Drug distributed in the polymer matrix as crystalline or amorphous
C-Drug enclosed in the polymer matrix yielding a core of the drug
encapsulated by a polymer layer.
The three morphologies are illustrated in fig. 1.5
Figure 1.5 illustration of three morphological models of drug-loaded
polymer nanfibers.
1 Morphology type
There is little interest in the morphology type 1, as the solubility of the
drug in the polymer limits the maximum drug loading possible. As the
mass of nanofiber mats in the implant will be small, they can carry only
impractically small amounts of most drugs. The release kinetics of
nanofibers where the drug is uniformly dissolved in the matrix can be
approximated by assuming the mat to be a collection of monodisperse
cylinders. with poorly soluble drugs, at higher loadings, the nanofibers
tend to form beads and the assumption may not always be a reasonable
Fig. 1.6 The drug is molecularly dispersed in the polymer matrix
2 Morphology type
The release of drug in this case was achieved primarily by enzymatic
biodegradation of the surface layers. The high porosity of nanofiber mats
(often exceeding ~90 %) facilitates rapid removal of any biodegradation
products in bio erodible systems minimizing possible hydrolysis. The
delivery process can be describes as follows. The drug initially dissolves
and saturates the polymer surrounding the particles embedded in the fiber
matrix. The dissolved drug invariably reaches the surface layer of the
fiber by diffusion and partitions into the aqueous boundary layer at the
fiber/buffer interface. Finally the drug molecules diffuse across the
boundary layer into the aqueous medium.
Fig. 1.7 diffusion of drug particles
Morphology type 3
Morphology type 3 has the distinct advantage over the other two in that
the drug or biological material ( such as protein or DNA ), does not come
into contact with aggressive spinning solvent, avoiding the possibility of
denaturing or other changes that alter their efficiency. Also, long-term
contact between the drug and the polymer, which can potentially lead to
reaction is avoided.
The kinetic features of drug release for these materials is expected to
qualitatively similar to that for nanofibers where drug particles are
distributed in the matrix.
Fig. 1.7 drug encapsulated in polymer matrix
1-4 Scaffolding application of nano fiber
Definition of scaffolds: Biomaterials, which may be natural or
artificially derived, providing a platform for cell adhesion and
transplantation. An important objective of tissue engineering is to
provide an alternative to conventional transplants (ultimately including
even entire functional organs) through the development of three
cellpopulated by an appropriate mix of dimensional polymer scaffolds
Live tissue comprises of collections of cells arranged in .tissueand
complex geometries within an extracellular matrix (ECM) that is in
plays a vital role in lending ECM The with cells. association intimate
of and is composed structural integrity to most types of tissue
glycosaminoglycan and fiber proteins such as the various types of
ECM plays a vital role in the transduction of chemical In addition to this
.differentiationnt and cellular signals that direct tissue developme
Polymer scaffolding is a synthetic substitute for the native ECM in the
body. As such nanofiber scaffolding must also provide a three
dimensional environment for cell adhesion and proliferation, guiding
Polymer ssue.growing cells to organize themselves into complex ti
scaffolding must meet the additional criteria of permeability, high
d high surface area for initial attachment of cells during the nporosity, a
.seeding stage
The main characteristics of scaffolding materials or synthetic ECM can
be readily anticipated:
1.The material in contact with the host body tissue should not elicit any
undesirable immune or tissue responses. the polymers selected and their
products of biodegradation should not interfere with the physiology of
the body tissue about it.
2.The material used should ideally biodegrade once initial tissue growth
has taken hold in the implant ( avoiding the need for a second invasive
surgery to remove it ).
3.Scaffloding topology should be conducive to attachment or
proliferation of cells and its pore-size distribution must match the
requirement of the cells being cultured on it.
4.The mechanical characteristics of the scaffolding material must match
those of the tissue with which it will interface.
5.In addition to mechanical support of cellular components, scaffolding
may also deliver growth factors or other molecules needed by the host
A consideration of these criteria and the observation that native body
tissue components (fibrin, actin, myosin, elastin, collagen) often tends to
have a fiber geometry suggest nanofiber mats to be particularly
promising materials for the construction of three dimensional
Electrospun nano fibers scaffolding can be fabricated out of:
1. Natural biopolymers such as collagen, fibrinogen, silk and
2. Synthetic polymers such as polyglycolides (PGA) , polylactdes(PLA)
3. Polymer blends of natural and synthetic polymers.
and compatibilitybioassures a certain degree of natural polymersUsing
Most biopolymers can be readily of the scaffold. biodegradability
electrospun into fibers and are beginning to be used in tissue engineering
Fig. 1.6 nanofiber scaffolds
1-5 Other applications
Wound care applications
Skin is the largest organ in the body, provides the first line of define
against infection. Damage to skin due to trauma (burns), although
capable of self-repair, often requires immediate medical intervention
depending on severity. wound dressing serve to protect the wound bed
from contamination or infection and remove from the body any exudates
generated during healing process. Natural wound healing initiates with
platelet adhesion, vascular constriction and leucocyte mobilization at the
site of wound, resulting in inflammation and clot formation. A desirable
high mechanical integrity, good gas wound dressing will therefore have
occluding, and be sufficiently sorbent -exchange capabilities , will be non
xudate . Although the presence of some amount of efor exudate control
promotes rapid wound healing and maintain a moist wound surface,
lowering the rate of infection, excessive exudate needs to be removed
from the bed. Nanofiber mats of selected polymers possess most of these
fig. 1.7 nano fiber wound
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