Innovation and Development of Study Field

Nanomaterials at the Technical University of Liberec

nano.tul.cz
These materials have been developed within the ESF
project: Innovation and development of study field
Nanomaterials at the Technical University of Liberec
 Technical University of Liberec

Nanofibers in medicine

2
 Outlook
 What is nanofiber
 Electrospinning
 Tissue engineering
 Applications of polymer nanofibers in medicine

3
 Nanofibers in the area of
nanotechnology

COTTON FIBER HUMAN HAIR POLLEN GRAIN

4
 What is a nanofiber?

Properties:
 Fibers with diameter in
nanometre range are called • large specific surface area
nanofibers, • high porosity
 Many types of polymers can • small pore size
be processed in the synthesis • diameter range (50 – 1000) nm
on nanofibers,
 50 to 1000 nanometres in
diameter - several orders of
magnitude smaller than fibers
synthesized by conventional
spinning methods.

● nanofibers and human hair

5 www.engr.utk.edu
 Surface to volume ratio
The smaller particles we subdivide, the more surface area is exposed.
Things that happen at surfaces, like heat transfer or chemical reactions,
happen faster.

6 http://www.uwgb.edu/dutchs/EarthSC202Notes/rockcycl.htm
http://ice.chem.wisc.edu
 History of electrospinning

Year Author Achievement

1914 Zeleny The first one observed spinning behavior of
conducting polymer solution in electric filed

1934 Formahl The first patent related to the electrospinning

process
1981 Larrondo and Manley Investigation of electrospinning using melted
polymer
1996 Reneker and Chun The probability of electrospinning using
different kind of polymer solutions was proved

2005 Jirsák,Sanetrník, Lukáš, NanospiderTM Technology

Kotek, Marinová

Zeleny, J. (1914). "The Electrical Discharge from Liquid Points, and a Hydrostatic Method of Measuring the Electric
7 Intensity at Their Surfaces". Physical Review 3 (2): 69 7
 Polymers used for electrospinning
John Zeleny
(1872-1951)
Czech-American physicist
Synthetics Natural

- Polyglycolic acid (PGA) - Elastin

- Polylactic acid (PLA) polymer - Collagen
- PGA - PLA solution - Fibrinogen
- Polydioxanone (PDO) - Chitozan
- Polycaprolactone (PCL)
- PGA - PDO
- PLA - PCL
- PDO - PCL

8 8
 Electrospinning technology
When a sufficiently high voltage is applied to a liquid droplet, the body of the
liquid becomes charged, and electrostatic repulsion counteracts the surface
tension and the droplet is stretched. At a critical point a stream of liquid erupts
from the surface. This point of eruption is known as the Taylor cone.

9 http://en.wikipedia.org/wiki/File:Electrospinning_Image_for_Wikipedia.tif
 Electrospinning technology
– process parameters

 Solution properties  Ambient parameters

 Viscosity  Temperature
 Conductivity  Humidity
 Surface tension  Air velocity
 Polymer molecular weight

 Controlled variables
 Flow rate
 Electric field strength
 Distance between tip and collector
 Needle tip design
 Collector chemical composition
 Geometry
● Variables of the electrospining process

10 http://en.wikipedia.org/wiki/File:Electrospinning_Image_for_Wikipedia.tif
 The Nanospider™ technology
Technology elaborated at the Technical University of Liberec, developed
in cooperation with ELMARCO s.r.o. , called Nanospider.

The scheme of NanospiderTM system

1. metal roller;
2. polymer solution;
3. reservoir;
4. Taylor cones;
5. fibers;
6. polypropylene non-woven fabric;
7. nanofiber sheet;
8. negative electrode.

11 Jirsák, Sanetrník, Lukáš, Kotek, Marinová: A method of nanofibres production from a polymer solution using
electrostatic spinning and a device for carrying out the method, EUROPEAN PATENT WO 2005/024101 11
 The Nanospider™ technology
Nanospider™ technology is a patented,
needle-free high voltage, free liquid surface
electrospinning process. The technology is
based upon the discovery, that it is possible to
create Taylor Cones and the subsequent flow
of material not only from the tip of a capillary,
but also from a thin film of a polymer solution.
● Electrospinning from a rotating electrode

● Various types of spinning electrodes

12 www.elmarco.com
● Schematic of the final product
 Applications of polymer nanofibres

13 Z.-M. Huang et al. / Composites Science and Technology 63 (2003) 2223–2253

 Applications of polymer nanofibres
- tissue engineering
Tissue engineering, also
called regenerative medicine
is an interdisciplinary field
involving knowledge from
medicine, biology, engineering
and materials science fields.
Tissue engineering makes use
of scaffolds to provide support
for cells to regenerate new
extra cellular matrix which has
been destroyed by disease,
injury or congenital defects
without stimulating any
immune response.
● Principle of tissue engineering

14 http://en.wikipedia.org/wiki/Tissue_engineering
S. Agarwal et al. / Polymer 49 (2008) 5603–5621
 Applications of polymer nanofibers
- tissue engineering
Objectives
• ECM (Extracellular Matrix) microenvironment key to tissue
regeneration
• Cell not considered as a self-contained unit

Role of ECM
• Scaffold element, responsible for keeping the shape of cells and their
appropriate location in the 3D structure

Ideal ECM
• non-immunogenic
• promote growth
• maintain 3-D structure
• biodegradable, only native tissues remain post-treatment

15
 Applications of polymer nanofibers
- tissue engineering
The cells binding to scaffolds with
microscale architectures flatten and
spread as if cultured on flat surfaces.
The scaffolds with nanoscale
architectures have bigger surface
area for absorbing proteins and
present more binding sites to cell
membrane receptors. The adsorbed
proteins further can change the
conformations, exposing additional
binding sites, expected to provide an
● Nanofibrous scaffolds causes that cells
edge over microscale architectures are more naturally constrained
for tissue generation applications.

16 S. Agarwal et al. / Polymer 49 (2008) 5603–5621

 Applications of polymer nanofibers
- tissue engineering
The use of electrospinning in the field of tissue engineering
is mainly focused at:

• Formation of non-woven mats of different biomaterials to biomimic

physical dimensions of native ECMs.,
• Proper choice of biomaterials in terms of mechanical properties and
degradation time which depends upon the type of scaffold,
• Type of the tissues to be regenerated and their regeneration time,
• Synthesis of the novel biomaterials that are designed to direct the
organization, growth, and differentiation of cells in the process of forming
functional tissues,
• Modification of the electrospinning process for the mimicking of extra
cellular matrix providing enhanced proliferation and differentiation of
cells.

17 S. Agarwal et al. / Polymer 49 (2008) 5603–5621

 Applications of polymer nanofibers
- tissue engineering

Chitosan / PEO nanofibers

promoted the adhesion of
chondrocyte and osteoblast
cells that maintained their
characteristic cell morphology
and thus cell phenotype. This
proves that they may serve as
a potential candidate for bone
tissue engineering.

● Images of osteoblasts (A and B) and chondrocytes

(C and D) seeded on nanofibrous membranes of
chitosan/PEO(90/10) after 5 days culture
18 N. Bhattarai et al. / Biomaterials 26 (2005) 6176–6184
 Applications of polymer nanofibers
- wound dressing

2 weeks
Electrospinned collagen scaffolds can be
used to fabricate skin substitutes with
optimal cellular organization.
Electrospinned scaffolds have been
shown to produce skin substitutes with
similar cellular organization, proliferation,

8 weeks
and maturation to the current, clinically
utilized model and were shown to reduce
wound contraction, which may lead to
reduced morbidity in patient outcomes.

● Grafts on athymic mice 2 and 8 weeks after

grafting. Skin substitutes fabricated using
freeze-dried electrospun collagen
19 H.M. Powell et al. / Biomaterials 29 (2008) 834–843
 Applications of polymer nanofibers
- wound dressing

 Aids the formation of normal skin growth

 Allows the air exchange
 Prevent the formation of scar tissue
 Prevent the bacterial colonization
 May be a drug delivery system

20
 Applications of polymer nanofibers
- artificial organs
Nanofiber scaffolds have the potential to pave the way for tremendous
scientific discoveries by not only providing in vitro 3D culture models, but
also by facilitating regenerative medicine and the synthesis of artificial
organs. Since the body naturally consists of a nanofibrous environment,
the synthetic nanofiber scaffold structure lends itself well to the tissue
engineering of hollow organs such as blood vessels, trachea, etc.

● A) Decellurized mouse lung; B) Tissue culture polystyrene; C) Nanofiber scaffold

http://www.sigmaaldrich.com
21 Sravya Vajapeyajula Nanofiber Scaffold Technology Validated in a Historic Human Implant Biowire Spring 2012
 Applications of polymer nanofibers
- artificial organs

The first synthetic nanofiber

human trachea was implanted
in November 2011 in Sweden.
The patient, from Maryland,
was a 30-year-old man with a
rare form of tracheal cancer
that required the removal of his
entire trachea. The removed
● Artificial trachea after fabrication and just
organ was replaced with a before implantation.
nanofiber trachea that was
infused with the patient’s bone
marrow stem cells.

http://www.sigmaaldrich.com
22
Sravya Vajapeyajula Nanofiber Scaffold Technology Validated in a Historic Human Implant Biowire Spring 2012
 Applications of polymer nanofibers
- artificial organs

Rabbit aortoiliac bypass procedure

involving a composite graft made of
electrospun poly(caprolactone)-collagen.

(A) The grafts were sutured end-to-side

between native aorta and native iliac
artery, with the ligation of proximal iliac
artery to redirect flow into the composite
graft;

(B) a representative operative image.

23 D.B. Khadka, D.T. Haynie / Nanomedicine: Nanotechnology, Biology, and Medicine 8 (2012) 1242–1262
 Applications of polymer nanofibers
- drug delivery

Physical drug loading on the surface of electrospun nanofibers.

Drug-friendly physical immobilization on the surface can be achieved by

using surface-modified prefabricated nanofibrous meshes that have an
extremely high surface area to volume ratio, resulting in higher drug
loading amount per unit mass than any other devices. The immediate
release of drugs from the nanofiber surface can enable facile dosage
control of some therapeutic agents, suitable for some specific
applications such as prevention of bacterial infection occurring within
few hours after surgery.

24 H.S. Yoo et al. / Advanced Drug Delivery Reviews 61 (2009) 1033–1042

 Applications of polymer nanofibers
- drug delivery

Physical surface adsorption is the simplest

approach for loading drug on the nanofibrous
mesh. Generally, electrostatic interaction,
hydrogen bonding, hydrophobic interaction,
and van der Waals interaction can be used as
a driving force for surface adsorption.

25 H.S. Yoo et al. / Advanced Drug Delivery Reviews 61 (2009) 1033–1042

 Applications of polymer nanofibers
- drug delivery

The large interfacial area of the nanofibers can enable the fabrication of
high-performance devices. Such hierarchical nano-structure can also
be constructed using therapeutically or biologically functional
nanoparticles such as silver or hydroxyapatite nanoparticles.

26 H.S. Yoo et al. / Advanced Drug Delivery Reviews 61 (2009) 1033–1042

 Applications of polymer nanofibers
- drug delivery
Layer-by-layer (LbL) polyelectrolyte multilayer assembly. The method comprises
of alternative layer-by-layer deposition of polyanions and polycations principally
driven by an electrostatic force on charged substrates, resulting in self
assembled multilayer coating or free standing film. This technique has attracted
considerable attention due to the ease of its synthesis, universality for any
complex structure of substrate, and the possibility of using any composition for
the coating layer.

27 H.S. Yoo et al. / Advanced Drug Delivery Reviews 61 (2009) 1033–1042

 Applications of polymer nanofibers
- tissue engineering / drug delivery

Tissue engineering application is often combined with drug delivery strategy.

28 H.S. Yoo et al. / Advanced Drug Delivery Reviews 61 (2009) 1033–1042

 Airbrushed nanofibers
Airbrushing could produce nanofibers from a wide range of polymers and
onto a wide range of targets. Airbrushing is safer, 10-fold faster,
100-fold less expensive to set-up and able to deposit nanofibers onto a
broader range of targets than electrospinning.

● The commercially ● Airbrushing can “paint” nanofibers onto irregularly

available airbrush shaped objects made from a wide range materials

The preliminary results highlight the advantages and disadvantages of

airbrushing versus electrospinning nanofiber scaffolds and demonstrate
that airbrushed nanofiber scaffolds can support stem cell differentiation.

29 W. Tutak et. all, Biomaterials 34 (2013) 2389 - 2398