Synthesis of High-Strength

Microcrystalline Cellulose
Hydrogel
Dwini Normayulisa P
Matthew Hardhi
Mauhibah Yumna
 OUTLINE
Methods of Hydrogel
Hydrogel
Synthesis

Classification of Hydrogel Material Properties of

Cellulose Hydrogel

Microcrystalline Cellulose Synthesis parameter of

Hydrogel Cellulose Hydrogel

Application of MCC
Hydrogel Paper Discussion
 1
Hydrogel
Hydrogels were the first biomaterials
designed for use in the human body
 “
Hidrogel adalah salah satu jenis makro molekul
polimer hidrofilik yang berbentuk jaringan
berikatan silang, mempunyai kemampuan
mengembang dalam air (swelling), serta
memiliki daya diffusi air yang tinggi.
Aplikasi Hidrogel
Hidrogel disintesis untuk digunakan sebagai;
◎ Matriks pelepasan obat
◎ Kontak lensa
◎ Immobilisasi enzim dan sel
◎ Pembalut luka bakar
 2
Classification of Hydrogel
Products
The hydrogel products can be classified on
different bases
Classification

According to
Based on
polymeric
source
composition

Based on Based on type

configuration of cross-linking

Based on According to
physical network
appearance electrical charge
 Based on source
Natural Hydrogel
◎ Polymers used in naturally
derived hydrogels are often
used in tissue engineering
as they are either
components of natural
extracellular matrix or have
similar properties.
◎ Frequently used polymers in
hydrogels are collagen,
hyaluronic acid, alginate,
chitosan, etc.
Synthetic Hidrogel
◎ Synthetic polymer
hydrogels constitute a
group of materials, used
in numerous biomedical
disciplines applications.
◎ Example of modified
polymer: Cuprophan,
cross-linked Dextrans,
and cross-linked
enzymatically treated
collagens.
 According to polymeric composition
Homopolymeric Copolymeric Multipolymer

◎ Polymer network ◎ Comprised of two or ◎ Made of two

derived from a more different independent cross-
single species of monomer species with linked synthetic and/or
monomer, which is at least one hydrophilic natural polymer
a basic structural component component, contained
unit comprising of ◎ Arranged in a random, in a network form.
any polymer block or alternating ◎ Component is a non-
network. configuration along the cross-linked polymer
◎ Have cross-linked chain of the polymer
skeletal structure network
Based on configuration

Amorphous (non-crystalline)

Semicrystalline

Crystalline
Based on type of cross-linking

◎ Hydrogels can be divided into two categories

based on the chemical or physical nature of
the cross-link junctions.

◎ Chemically cross-linked networks have

permanent junctions, while physical networks
have transient junctions that arise from either
polymer chain entanglements or physical
interactions such as ionic interactions,
hydrogen bonds, or hydrophobic interactions
Based on physical appearance

Hydrogels appearance as;

◎ Matrix,
◎ Film, or
◎ Microsphere

It depends on the technique of

polymerization involved in the preparation
process.
According to network electrical charge

The basis of presence or absence of electrical

charge located on the cross-linked chains;
◎ Nonionic (neutral)
◎ Ionic (Inc, anionic or cationic)
◎ Amphoteric electrolyte
◎ Zwitterionic
According to network electrical charge

◎ Hydrogel-forming natural polymers include

proteins such as collagen and gelatine and
polysaccharides such as starch, alginate, and
agarose.
◎ Synthetic polymers that form hydrogels are
traditionally prepared using chemical
polymerization methods.
 3
Micro-Crystalline Cellulose
Hydrogel
Definition
 “
Microcrystalline cellulose is a pure partially
depolymerized cellulose synthesized from
alpha-cellulose precursor, obtained as a pulp
from fibrous plant material or bacterial
Micro-Crystalline Cellulose
(MCC) Hydrogel
Hydrogel synthesized by cellulose
with micro-crystalline structure

Cellulose is a suitable biopolymer for

hydrogel due to its mechanical
strength

Cellulose exhibits high strength, high

stiffness, and low density
 4
Application of Micro-
Crystalline Cellulose
Hydrogel
Bio-related application
Bio-related application of
MCC Hydrogel
Tissue
Drug delivery Biomedical
engineering
carriers devices
scaffolds

Membrane Hygiene
Biosensor
separation products

Pollutant
Agriculture
adsorbent
 Bio-related application of
MCC Hydrogel

Contact lenses Wound dressing

Diapers Drug delivery carriers

 5
Various Methods
On Hydrogel Synthesis
 • Hydrogen Bonds
• Crystallization
Physical • Ionic Interaction
• Protein Interaction

• Complementary Groups
• Aldehydes
• Condensation
Chemical • Addition
• High-Energy Radiation
• Free Radical Polymerisation
• Enzymatic Cross-Linking

Cross-linkers used in hydrogel preparation should be extracted from the

hydrogels before use due to their reported toxicity
 6
Material Properties
Of Cellulose Hydrogel
Mechanical Water
strength content

Optical Thermal
transparency stability

Elasticity Morphology
 7
Synthesis Parameter
Of Cellulose Hydrogel
 Activation Dissolution
time time

Relative Cellulose
humidity concentration

Type and
Viscosity of
concentration
solution
of solvent
 8
Paper Discussion
Synthesis of High-strength
Microcrystalline Cellulose Hydrogel
by Viscosity Adjustment
 Hydrogels
Hydrogel often limited in practical
application because of their poor
mechanical properties (ex: contact
lenses, drug delivery carries, and
artificial tissues require high strength)
Cellulose
Cellulose is a suitable biopolymer
with good properties and
characterization like biodegradability,
biocompatibility, and renewability for
bio-related application
Solvent System
Cellulose dissolving solvent system
belong to four categories: polar
solvents, ionic liquids, deep eutectic
solvents, and alkali aqueous systems.
TBAF/DMSO
TBAF/DMSO is a polar solvent that
suitable for practical bio-related
applications because it is relatively
non-toxic and inexpensive.
 1. Dissolution
Step Process 2. Curing
Goals 3. Exchange

The synthesis of a high-strength native

cellulose hydrogel by controlling the
solution viscosity of microcrystalline
cellulose (MCC) and TBAF/DMSO.

Result

Identified the cellulose hydrogel with the

highest strength and analyzed its
physicochemical properties, such as its
crystallinity, thermal stability, degree of
polymerization (DP), and morphology,
 9
Method
The Chosen Methodology
 Materials Source
• Micro-Crystalline Cellulose
(Avicel PH-101, mean DP 170)
Sigma-Aldrich Co. (St. Louis, MO,
• TBAF (Tetrabutylammonium)
USA)
• DMSO (Dimethyl Sulfoxide)
• Sodium Sulfate
• Sodium Potassium Tartrate
(Rochelle salt)
• Copper (II) Sulfate
Duksan Co. (Seoul, Korea)
• Sulfuric Acid
• Sodium Carbonate
• Sodium Bicarbonate
• Ammonium Molybdate
Daejung Co. (Seoul, Korea)
Tetrahydrate
• Disodium Hydrogen Arsenate
Wako Ltd. (Osaka, Japan).
(Hepta-Hydrated)
 Hydrogel Synthesis

Dissolution Exchange
• The cellulose solution thickened due to
physical entanglement and slow
aggregation of the cellulose molecules

• MCC is dissolved in TBAF/DMSO • A high-strength cellulose hydrogel was

• Solution viscosity is adjusted by tuning achieved by exchanging TBAF/DMSO
the ratio of MCC and TBAF with water and rearranging cellulose
concentrations in DMSO Curing molecules.
 ANALYSIS

◎ Identification of cellulose
hydrogel with the highest
strength.
◎ The mechanical strength
of hydrogels synthesized
in varying compositions of
MCC and TBAF.
◎ Crystallinity
◎ Thermal Stability
◎ Degree of Polymerization
◎ Morphology
 10
Synthesis of high-strength
microcrystalline cellulose
hydrogels
 1. Dissolution
• MCC was solved with TBAF in DMSO at a specific ratio at room temperature.
• Cellulose solution will be transparent for indicate that MCC completely dissolved and
homogenously dispersed.
• The result, cellulose solution was poured into silicone molds and left to cure overnight

2. Curing
• The solution thickened and formed an aggregate, due to an increase in the physical
networks because of self-association forces between cellulose molecules.
• The aggregate efficiently induces the slow rearrangement of cellelose chains and
sheets required for proper gelation that results in a dense structure of the hydrogel.

3. Exchange
• HS-MCC hydrogel was produced through a solvent exchange process by soaking the
aggregate in water to thoroughly replace the TBAF/DMSO in the aggregate with water.
• The displacement of fluoride ions by water causes the subsequent reformation of
hydrogen bonds between cellulose chains
The complete removal of the TBA+, F- ions and DMSO from the
hydrogel was confirmed by elemental analysis of nitrogen and sulfur
originating from the TBA+ and DMSO, showed on Table 1.
 11
Controlling the viscosity of
cellulose solutions
to synthesize the strongest
high-strength microcrystalline
cellulose hydrogel
Influence of viscosity against
strength
Viscosity of the molten state
of a polymer is highly
correlated with the
mechanical strength of the
polymer
Similar correlation between
the viscosity of cellulose
solutions, formation of an
LCP, and the mechanical
strength hydrogels
Formation of an LCP (liquid
crystalline phase) in the
solution is known to
enhance its viscosity
As MCC is the polymer, and
TBAF is a strong electrolyte
crucial for dissolving MCC,
the viscosity of the cellulose
solution strongly depends on
their compositional ratio in
DMSO
Viscosity of Cellulose Solutions
with Different Compositions

Compositions of MCC are 0.6-

2.5%

Compositions of TBAF are

0.6-2.5%

Viscosity of cellulose solutions

with a 1:1 mass ratio of
TBAF to MCC was relatively
higher
Viscosity of cellulose solutions
with various amounts of MCC
(0–5.0%) at a constant amount of
TBAF (2.5%)

Solution viscosity increased

with an increasing MCC
content up to 5.0%

Compositions of TBAF are

0.6-2.5%

Viscosity of cellulose solutions

with a 1:1 mass ratio of
TBAF to MCC was relatively
higher
Viscosity of cellulose solutions
with with various amounts of TBAF
(0–31.6%) at a constant amount of
MCC (2.5%)
Solution viscosity dramatically increased
with an increasing TBAF content up to 3.5%
and decreased above 3.5%

At TBAF contents greater than 3.5%, we

expect that the lack of the ion–induced
dipole interactions of TBA+, F− ions and
MCC due to their concentration imbalance
caused the viscosity of cellulose solution to
stop increasing.

Highest viscosity was obtained from 2.5%

MCC and 3.5% TBAF within our selected
range.
 “
Highest viscosity was obtained from
2.5% MCC and 3.5% TBAF
 12
Mechanical properties
high-strength microcrystalline
cellulose hydrogels
Mechanical properties of HS-MCC
In order to compare the
mechanical strengths of the
hydrogels, the compressive
modulus of the HS-MCC
hydrogels were measured with
a texture analyzer
Compressive strength was
examined by observing their
endurance to uniaxial
compression as well as
obtaining a stress–strain
curve.

Hydrogels formed from the

most viscous cellulose solution
of 2.5% MCC and
approximately 3.5% TBAF
exhibited a high compressive
modulus, the highest of which
was 0.44 MPa
 The strongest HS-MCC
hydrogel endured pressure
without deforming regardless
of different shape and
maintained its original height
with or without a
counterweight

Thereby exhibiting high

The strongest HS-MCC hydrogel under rigidity and resilience to
the mechanical stress of a external mechanical stress
counterweight
 The strongest HS-MCC
hydrogel sustained a
compressive strain of
37% without breaking,
measured with the
texture analyzer

The compressive
strength of the strongest
A stress–strain curve of the strongest HS-MCC hydrogel was
HS-MCC hydrogel under uniaxial quantitatively analyzed to
compression be 0.38 MPa
 This relationship indicated
that the strength of the HS-
MCC hydrogel is strongly
influenced by the viscosity of
the cellulose solution,
exhibiting a positive linear
correlation

Correlation between the viscosity of

cellulose solutions and the compressive
modulus of HS-MCC hydrogels. The
cellulose solutions were prepared with
2.5% MCC and different amounts of
TBAF (1.3–31.6%) in DMSO
 “
The more viscous the cellulose
solution was, the stronger the
hydrogel became
 13
High-Strength MCC Hydrogels
Physicochemical Properties
 PREPARATION of HS-MCC HYDROGEL (1)

Cellulose solutions were prepared composed of varying MCC and

TBAF ratios in DMSO.
• MCC = 2.5% (w/v)
• TBAF = 1.3–31.6% (w/v)

Appropriate amount of TBAF was first added into a 50-mL conical tube
containing DMSO, and then MCC was added to each solution.
• This is to ensure good dispersion.

MCC was dispersed in each TBAF/DMSO solution and stirred at room

temperature for 1 h.
• Well dissolved MCC results in a transparent solution.

Resulting cellulose solution was poured into a silicone mold and left
overnight at room temperature until aggregated into a thickened gel.
 PREPARATION of HS-MCC HYDROGEL (2)

The aggregate was removed from the mold and soaked in

water for 10 h to transform the aggregate into a hydrogel
through a solvent exchange.

To completely remove the TBAF and DMSO from the HS-

MCC hydrogel, it was soaked in water for an additional 5 h,
during which the water was exchanged every 1 h.

After rinsing five more times with running water, the

HSMCC hydrogel was finally obtained.
 Crystallinity was analyzed in Crystallinity Index (CI)
Values calculated from the XRD data.

Crystallinity

Thermal
Stability

Degree of
Polymerization

Morphology
“
The CI values of MCC and the strongest HS-MCC
hydrogel were 73.4% and 1.4%, respectively.
“
“ “
The strongest and other HS-MCC hydrogels exhibited a
broad and flat peak indicating amorphous phases.

“ “
In contrast, MCC exhibited distinct peaks at diffraction
angles of 14.9–16.3°, 22.5° and 34.5°.
“ “
This was further confirmed by FT-IR analysis using the
sensitivity of the Lateral Order Index (LOI) (i.e.,
A1430/A897) to changes in crystallinity

“ “
The LOI value of cellulose decreased from 1.86 to 0.73,
corresponding to the changing CI pattern.
 CONCLUSION

In the strongest HS-MCC hydrogel, the crystalline

structure of MCC was transformed to an
AMORPHOUS phase during the dissolution step.
 The thermal decomposition of MCC and the strongest
HS-MCC hydrogel was compared using TGA to
examine their respective thermal stabilities.

Crystallinity

Thermal
Stability

Degree of
Polymerization

Morphology
 Their TGA curves almost overlapped at approximately
350 °C, with an identical onset temperature of 315 °C.

Crystallinity

Thermal
Stability

Degree of
Polymerization

Morphology

The apparent similarity of the thermal stabilities of both hydrogel suggests that
high thermal stability of MCC is well-preserved throughout the three-step
synthesis of the strongest HS-MCC hydrogel.
 The number of monomeric units in
a macromolecule or polymer or oligomer molecule

Crystallinity

Thermal
Stability

Degree of
Polymerization

Morphology

DP test is done to examine the degradation of MCC during

the hydrogel synthesis.
 The DP values of MCC and the strongest HS-MCC hydrogel
were 170 and 157.

Crystallinity
The difference between the DP values was not statistically
significant, which is consistent with the results of a previous
Thermal report demonstrating that the DP of cellulose is not reduced
Stability by dissolution in TBAF/DMSO for 24 h at 60 °C.

Degree of
Polymerization Reducing the DP generally weakens the hydrogel strength,
but the DP was the same before and after our three-step
process.
Morphology

Consequently, the increase in the strength of our strongest

HS-MCC hydrogel was probably not affected by DP change.
 Closely intertwined
microfibrils.

Crystallinity

Thermal
Stability

Degree of
Polymerization

Morphology

Densely packed spherical particles or

fibrous structures, depending on the
TBAF concentration.
 Similar to those found in
other cellulose hydrogels
with high mechanical
strength.
Crystallinity

Thermal
Stability

Degree of
Polymerization

Morphology

More compact structure with

spherical particles around 80 nm
in size.
 The nano-size of the cellulose particles is
possibly responsible for the high strength
of the strongest HS-MCC hydrogel.
Crystallinity
• The small size increases the specific surface area
• Also decreases the interstices between the
Thermal nanoparticles.
Stability

Degree of
Polymerization

Morphology
The strongest HS-MCC hydrogel had a more densely packed
structure by nano-sized spherical particles

It also has an amorphous phase

Thermal stability and DP were unaffected.

The more compact structure found in the strongest HS-MCC

hydrogel contributes to the improved mechanical properties.
 14
High-Strength MCC Hydrogels
Effect of Viscosity Adjustment to the
Cellulose Solution
Conclusion: Solution Viscosity Affects HS-MCC Hydrogel Strength.
 Particle
Size

Phase Molecular
Viscosity
Type Structure

Liquid
Crystalline
Phase
(LCP)
Formation
Graphical Representation
 MCC = Spheres
Cellulose chains tend to aggregate
into particles when dissolved in
TBAF/DMSO

Graphical Representation
 Fluoride Ions
Affect the degree of dissolution by
breaking the intermolecular interactions
(Hydrogen bonds, van der Waals
forces, and hydrophobic interactions in
cellulose)

Graphical Representation
 Number of Dissolved MCC Particle

Graphical Representation
 Formation of LCP
At specific concentration ratio
of MCC and TBAF.

Graphical Representation
 Optimal TBAF Concentration Range = 2.5–3.8%
◎ Particle size ~ 100 nm
◎ Total number of cellulose particles increases =
higher viscosity.
◎ HS-MCC hydrogels in this range were
transparent due to small particle size (avoids light
scattering).
◎ Formation of LCP also contributes to the high
viscosity of the solution and the high mechanical
strength of the HS-MCC hydrogels.
 Low TBAF Concentration Range = (1.3–2.2%)
◎ Lack of TBA+ and F− ions resulted in the
inefficient disbanding of intermolecular networks.
◎ Particle size remained large.
◎ Less cleavage of MCC = Fewer particles in the
solution = Decreased viscosity.
 High TBAF concentration range = 4.4–31.6%
◎ Amount of TBA+ and F− ions increase greatly
(proved by electrical conductivity test).
◎ Numerous amount of ions = Prevention of the
cellulose chains from bonding strongly with each
other
◎ Presence of the excess ions may lead to a
decrease in the solution viscosity.
References
◎ Choe, D., et al. 2017. Synthesis of high-strength microcrystalline cellulose hydrogel by
viscosity adjustment. Seoul, South Korea: Elsevier.
◎ Ahmed, Enas M. 2013. Hydrogel: Preparation, characterization, and applications: A review.
Department of Chemical Engineering & Pilot Plant, National Research Centre, Dokki, Giza,
Egypt: Journal of Advance Research.
◎ Ahn, Y., Kwak, S.-Y., Song, Y., & Kim, H. (2016). Physical state of cellulose in Bmim Cl:
Dependence of molar mass on viscoelasticity and sol-gel transition. Physical Chemistry
Chemical Physics, 18, 1460–1469.
◎ Biganska, O., & Navard, P. (2005). Kinetics of precipitation of cellulose from cellulose-
NMMOwater solutions. Biomacromolecules, 6, 1948–1953.
◎ Calvert, P. (2009). Hydrogels for soft machines. Advanced Materials, 21, 743–756.
◎ Chang, C., Zhang, L., Zhou, J., Zhang, L., & Kennedy, J. F. (2010). Structure and properties of
hydrogels prepared from cellulose in NaOH / urea aqueous solutions. Carbohydrate Polymers,
82, 122–127.
◎ Choe, D., & Shin, C. S. (2015). Gelation and decrystallization of cellulose by TAAHs/DMSO
treatment and the role of anions and cations. Cellulose, 22, 3013–3025.
◎ Gericke, M., Schlufter, K., Liebert, T., Heinze, T., & Budtova, T. (2009). Rheological properties
of cellulose/ionic liquid solutions: From dilute to concentrated states. Bio macromolecules, 10,
1188–1194.
◎ Heinze, T., Dicke, R., Koschella, A., Kull, A. H., Klohr, E. A., & Koch, W. (2000). Effective
preparation of cellulose derivatives in a new simple cellulose solvent. Macromolecular
Chemistry Physics, 201, 627–631.