Chitosan and/or Cellulose

Yolda SEK
Faculty of Arts & Sciences
Chemistry Dep
http://kisi.deu.edu.tr/yoldas.seki
Chitosan
Chitosan (2-amino-2deoxy-(14)--D-
glucopyranan), a polyaminosaccharide,
normally obtained by alkaline deacetylation of
chitin is the principal component of living
organisms such as fungi and crustacea.
What is the importance of DA?
You will buy Chitosan
The degree of N-acetylation (DA) together with
the molecular weight are the most important
parameters for its characterization. The DA,
which is by definition the molar fraction of N-
acetylated units, is a structural parameter
influencing charge density, crystallinity and
solubility, including the propensity to
enzymatic degradation, with higher DAs
leading to faster biodegradation rates
What are the properties of Chitosan
?
1- Chitosan is a linear polymer of mainly anhydroglucosamine which
behaves as a linear polyelectrolyte at acidic pH
2- Chitosan is nontoxic and bioabsorbable.
3- At pH below 6.5, chitosan in solution carries a high positive charge
density, one charge per glucosamine unit.
4- Since chitosan is one of the few cationic polyelectrolytes, it is an
exception to the current industrial high molecular weight
polysaccharides, which are mostly neutral or polyanionic.
What are the biomedical applications?
Chitosan is being evaluated in a number of
biomedical applications icluding wound
healing and dressing, dialysis membranes,
contact lenses, fibers for digestible sutures,
liposome stabilization agents, antitumor uses
and drug delivery uses and controlled-release
systems
In these uses chitosans key properties
are :
1) biocompatibility
2) nonantigenicity
3) nontoxicity (its degradation products are
known natural metabolites)
4) the ability to improve wound healing/or clot
blood
5) the ability to absorb liquids and to form
protective films and coatings, and
6) selective binding of acidic liquids, thereby
lowering serum cholesterol levels.
How can Chitosan be used in
orthopedics?
1- Its enzymatic degradability associated to
its structural similarity to extracellular matrix
glycosaminoglycans makes it an attractive
biopolymer for bone tissue repair.
2- Numerous bone filling materials have been
developed in which chitosan is used in
combination with calcium
phosphates,essentially as a binding agent, or
associated to biological signaling molecules
Can Chitosan be used as nonprotein
temporary scaffold?
In addition, its versatility to be processed
into injectable, porous and membran
forms without use of toxic solvents makes
chitosan an interesting material to be used as
a non-protein temporary scaffold, for bone
regeneration . Presently, an increasing
number of anchorage-dependent cells,
including bone cells, are being cultured on
2-D and 3-D chitosan-based matrices,
envisaging cell-based regenerative
therapies.
What is the effect of DA of chitosan on
cell properties?

Cell adhesion, migration and cell growth

kinetics of a number of cells, including
keratinocytes and fibroblasts, are
known to depend on the DA of
chitosan, lower DAs favoring cell
adhesion. However, no osteoblast
adhesion studies have been reported.
 What is P-Chitosan ?
Does P-Chitosan nucleate calcium
phosphate ?
The ability of phosphorylated chitosan
(P-chitosan) membranes to nucleate
calcium phosphates under simulated
physiologic conditions, was investigated
What is the procedure ?
The membranes M.A. Barbosa et al. /
ITBM-RBM 26 (2005) 212217 215
were immersed in Ca(OH)2 or NaOH
solutions, in order to obtain the Ca or
the Na salts, respectively.
What is the result?
SEM-EDS studies revealed the
presence of a calcium phosphate
mineral layer all over the surface of P-
chitosan membranes, after incubation in
Ca(OH)2 solution.
 What else ?
During the immersion in simulated body
fluid (SBF), a multilayered porous
mineral structure composed of a
partially carbonated and poorly
crystalline apatite was formed on the
surface of these membranes,
But chitosan ( Drawbacks??)
has some drawbacks, it is only soluble
in aqeous medium in the presence of a
small amount of acid such as AcOH and
its mechanical properties are not good
for some biomedical application.
Therefore many researchers tried to
modify its properties.
How can chitosan be modified ?
In the past few years

a number of publications appeared on

the blending of chitosan with various
polymers such as poly(vinyl alcohol)
(Mucha & Pawlak, 2005; starch
(Pawlak & Mucha, 2003), cellulose Wu,
Yu, Mi, Wu, Shyu and Peng, 2004) and
its derivatives (Mucha & Pawlak, 2005;
Pawlak & Mucha, 2003), etc
Celulose

The cellulose molecule (C6H10O5)

What is the monomer of Cellulose ?
Cellulose monomers (-glucose) are
linked together through 14 glycosidic
bonds by condensation
What is the source of Cellulose ?
Cellulose is a common material in plant
cell walls
Cellulose is found in plants as
microfibrils (2-20 nm diameter and 100 -
40 000 nm long). These form the
structurally strong framework in the cell
walls
Cellulose is the most abundant form of
living terrestrial biomass
What is the most common biopolymer
on Earth?

The primary cell wall of green plants is

made primarily of cellulose; the
secondary wall contains cellulose with
variable amounts of lignin. Lignin and
cellulose, considered together, are
termed lignocellulose, which (as wood)
is the most common biopolymer on
Earth.
What are the variations among cellulose
types ?
Given a cellulose material, the portion
that does not dissolve in a 17.5%
solution of sodium hydroxide at 20 C is
cellulose, which is true cellulose; the
portion that dissolves and then
precipitates upon acidification is &beta
cellulose; and the proportion that
dissolves but does not precipitate is
&gammal cellulose.
How can we assay Celloluse ?
Cellulose can be assayed using a
method described by Updegraff in 1969,
where the fiber is dissolved in acetic
and nitric acid, and allowed to react with
anthrone in sulfuric acid. The resulting
coloured compound is assayed
spectrophotometrically at a wavelength
of approximately 635 nm.
What are the unique properties for
medical application?

Nontoxicity (monomer residues are not

hazardous to health), water solubility or
high swelling ability by simple chemical
modification, stability to temperature
and pH variations, and a broad variety
of chemical structures.
Biodegradable polymer
What is the other properties?
Ikada has described cellulose as a
polymer usually exhibiting relatively
low protein adsorption and cell
adhesion (particularly blood cells), low
immune response (low phagocytosis
by macrophages and low interleukin-1
release), and inducing comparatively
higher activation of the complement
system
 The second line of defense
includes four nonspecific
mechanical steps:
Phagocytes: also known as
leukocytes or white blood
cells, contain and destroy
pathogens by phagocytosis.
These include monocytes
that enlarge into gigaintic
phagocytic cells. These
phagocytic cells are called
macrophages and are known
as natural killer cells or NK
cells
 Steps of a macrophage ingesting a pathogen:

a. Ingestion through phagocytosis, a phagosome is formed

b. The fusion of lysosomes with the phagosome creates a
phagolysosome, the pathogen is broken down by enzymes
c. Waste material is expelled or assimilated (the latter not
pictured)
Parts:
1. Pathogens
2. Phagosome
3. Lysosomes
4. Waste material
5. Cytoplasm
6. Cell membrane
 Cellulose is poorly biodegradable in the
body and is not digestible, but it can be
made hydrolysable by changing its
higher order structure
What is the largest application ?
In medicine, membranes for blood
purification (haemodialysis) made of
cellulosics, are among the largest
applications of polymers in therapy [25].
Derivatives ?
The hydroxyl groups of cellulose can be
partially or fully reacted with various
chemicals to provide derivates with useful
properties. Cellulose esters and cellulose
ethers are the most important commercial
materials. In principle, though not always
in current industrial practice, cellulosic
polymers are renewable resources
What is regenerated cellulose hydrogels?
Baquey and coworkers have pioneered and
considerably contributed to this field of study
by firstly proposing the use of regenerated
cellulose hydrogels (RCH) for orthopedic
applications. Cellulose Regenerated by the
Viscose process (CRV) was patented and
thoroughly investigated in terms of physico-
chemical, mechanical and biological
properties. It was later chemically modified to
enhance its bioactivity through modifications
such as phosphorylation, grafting of adhesive
peptides and oxidation.
How is CRV produced ?
1- Briefly, the starting cellulose material (most
usually, refined wood pulp) is converted into
alkalicellulose by steeping in sodium
hydroxide, which is then aged.
2- Alkali cellulose is then converted into
sodium cellulose xanthate with carbon
disulfide, and finally the xanthate is dissolved
in dilute alkali, and viscose is regenerated
thereof.
3- Filtration and purification determine the
quality of the final product
Where is CRV used ?
CRV is highly stable to gamma sterilization
and ageing. It was investigated as
implantable material in orthopedic surgery, as
a sealing material for the femoral component
in hip prostheses, in place of the acrylic
cement.
It was envisaged to take advantage not only
of its biostability and good matching with
mechanical properties of cortical bone but
also of its hydroexpansivity, allowing therefore
a satisfactory fixation to hard tissue
The others
3- It is cytocompatible although it seemed
not to allow proliferation of bone cells, after
an initial attachment of the cells.
4- The biostability and osteoconduction of
this material have been demonstrated in
vivo, although a complete osseointegration
was not observed
What is CP?
1- The applicability of cellulose phosphate
(CP) as a biomaterial for orthopedic
applications was then investigated to
improve the osseointegration of cellulose.
2- CP has been used for decades in the
treatment of Ca metabolism-related diseases,
such as renal stones, due to its high Ca
binding capacity, associated with lack of
toxicity and indigestibility
Is CP promising alternative biomaterial ?
How was it synthesized?
Due to its capability of binding Ca and
eventually growth factors, CP can be
envisaged as a promising alternative
biomaterial, capable of promoting an
adequate healing response once
implanted.
CP was synthesized according to an
optimization of the
H3PO4/P2O5/Et3PO4/hexanol method
More about CP
In vitro biocompatibility studies in cultured
bone cells showed that CP is not
cytotoxic, independently of the
phosphate content. However, CP
promoted poor rates of cell attachment,
proliferation and differentiation, which
were attributed to the negative charge,
associated with the high hydrophilicity of
the cellulose derivative [32].
Finally about CP
Finally, animal implantation studies in
rabbits revealed the biocompatibility
of both unmodified and
phosphorylated cellulose, as well as
their osteoconductive properties. A
full osseointegration could not be
observed, although some remodeling
activity of the bone tissue was observed
when CP was used
What is cellulose viscose sponges ?
1- Martson et al. reported regenerated cellulose
viscose sponges as compatible implantable
tissue matrices for bone tissue
regeneration. They described this material
as slowly degradable .
2- Cellulose viscose sponges have also been
proposed as connective tissue
regeneration matrices. Taillac et al. [42,43]
are presently investigating the applicability of
oxidized and macroporous regenerated
cellulose structures for promoting cell
colonization of 3-D structures.
Where is Oxidized cellulose used ?
Oxidized cellulose is used as a wound
dressing and has been proposed for
bone regeneration [2730].
 Cellulosic materials are increasingly
used as reinforcements for
thermoplastic matrix composites, due to
advantages such as low cost, good
mechanical properties, low density,
biodegradability and availability of
renewable natural resources
Conducting polymer
The development of conducting polymer
composites with cellulose (wood) and
protein fibres (wool) with the polymer
fully encapsulating the fibre, provide the
opportunity to develop new hybrid
materials that exhibit the inherent
proprieties of both components.
 These properties include the tensile strength,
flexibility and relatively high surface areas
that are associated with cellulose (wood) and
wool fibres, and the electronic and chemical
properties of conducting polymers. The
resulting fibre-conducting polymer hybrid
materials can then be incorporated into other
commodity/consumer type materials such as
plastics,surface coatings and films to impart
new or enhanced properties to them.
Chitosan/cellulose
chitosan/cellulose acetate blend,with
cellulose acetate (CA) acting as a matrix
polymer and chitosan (CS) as a functional
polymer have been prepared
What are the properties of blend?
The preliminary study has indicated that
the blend hollow fiber membranes have
high mechanical strength, tunable
hydrophilicity/hydrophobicity and good
binding or adsorption capabilities toward
heavy metal ions or albumins, even at
the presence of a small amount of CS in
the blend hollow fiber membranes.
Which forms is it possible ?
Natural or chemically modified
polysaccharides, derived from cellulose
acetate or chitosan, have the ability to
be molded in different forms such as
films, fibers and spheres.
What kind of application ?
new hybrids embracing cellulose
acetate have been demonstrated to be
versatile in having numerous
applications such as in exchange
processes , as substrates for enzyme
immobilization , as semi-permeable
membranes
What is the difference and similarity?
Both biopolymers, -chitosan and
cellulose acetate, have very similar
structural backbones, differing in the
presence of either acetate or amino
groups distributed along the polymeric
chains, as shown schematically in Fig1
Cellulose ? Chitosan ?
Why is cellulose a blending material for
chitosan ?
The interest in using cellulose as a blending
polymer for chitosan arises from two facts: (a)
cellulose is the most abundant natural
biopolymer with relatively strong mechanical
strength of up to 1 GN/m2 (10,000MPa) [12],
and (b) cellulose has similar chemical
structures as chitosan, providing the
possibility of producing a homogeneous blend
that combine the unique properties of
chitosan and the good availability of cellulose
to make chitosancellulose hydrogel.
What is limitation of Chitosan ?
The major material limitation of the
hydrogel beads is however in their poor
acidic resistance and mechanical
strength.
How can the chemical stability of
chitosan improved ?
Attempts have been made to improve the
chemical stabilities of the hydrogel beads in
acidic conditions by chemical crosslinking of
the surface with crosslinking agents, such as
glutaricdialdehyde(GA), ethylene glycol
diglycidyl ether (EGDE),and epichlorhydrine
[4]. Chemical crosslinking reaction was found
to be able to reduce the solubility of chitosan
hydrogel beads in aqueous solutions of low
pH values.
Cellulose and
Jin and Bai [4] studied lead adsorption
with chitosan/polyvinyl alcohol (PVA)
hydrogel beads and found that the
blending of PVA in chitosan improved
the mechanical strength of the hydrogel
beads.
Thank you