Hydrogels and Their Biomedical Uses 1 M. R. Naimi-Jamal 2013
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Hydrogels
and Their Biomedical Uses
1
M. R. Naimi-Jamal
2013
Overview
Hydrogels – Structure – Swelling properties – Biomedical Uses
Common Hydrogels?
Can you think of hydrogels in your everyday life?
- Contact Lenses - Jello (a collagen gel ~ 97% water) - Extracellular matrix components - Polysaccharides - DNA/RNA - Blood clot
4
Applications of Hydrogels Soft contact lenses Pills/capsules Bioadhesive carriers Implant coatings Transdermal drug delivery Electrophoresis gels Wound healing Chromatographic packaging material
Hydrogels
“Hydrogels are water swollen, cross-linked polymeric structures produced by the simple reaction of one or more monomers or by association of bonds such as hydrogen bonds and strong van der Waals interactions between chains.”
-N. A. Peppas in Biomaterials Science (1996)
Other definitions
Water insoluble, three dimensional network of polymeric chains that are crosslinked by chemical or physical bonding
Polymers capable of swelling substantially in aqueous conditions (eg hydrophilic)
Polymeric network in which water is dispersed throughout the structure
7
Behavior of Hydrogels
No flow when in the steady-state By weight, gels are mostly liquid, yet they
behave like solids
They can absorb large quantities of water – May absorb up to 1000 times their dry
weight Cross linkers within the fluid give a gel its
structure (hardness) and contribute to stickiness (tack).
Volume degree of swelling (Q)
Q = actual sample volume in the swollen state volume in the dry state
Weight degree of swelling
= actual sample weight in the swollen state weight in the dry state
Based on structural features, hydrogels can be classified as...
Amorphous hydrogels – Randomly arranged macromolecular chains
Semicrystalline hydrogels – Dense regions of ordered macromolecular
chains (crystallites)
Hydrogen bonded hydrogels – 3-D network held together by hydrogen
bonds – Strong hydrophobic/hydrophillic interactions
Chemical Physical
Based on crosslinkers features, hydrogels can be classified as...
Chemical – Covalently crosslinked – Absorb water until they reach equilibrium
swelling (crosslink density dependent) – High stability in harsh environments (high
temp, acidic/basic and high stress)
Physical Non-covalently crosslinked Disordered networks are held together by
associative forces capable of forming non-covalent crosslinks (molecular entanglements, electrostatic interactions, hydrogen bonding, and hydrophobic interactions)
– Weaker and more reversible forms of chain-chain interaction
– Respond to physical changes (temperature, pH, ionic strength and stress)
Hydrogel Fabrication Chemical hydrogels Physical hydrogels
▪ Hydrogen bonding
▪ hydrophobic interaction
▪ crystallinity
▪ stereocomplex formation
▪ ionic complexation
Covalently crosslinked Noncovalently crosslinked
Thermoset hydrogels Thermoplastic hydrogels
Reliable shape stability and memory
Limited shape stability and memory
Physical crosslinking
• Ionic hydrogel
• Cross-linking without chemical reaction • ionic interaction, hydrogen bonding, antigen-antibody
interaction, supramolecular association
Chemical Hydrogels Methods
Co-polymerization of monomer and crosslinker – HEMA and EGDMA (Ethylene glycol dimethacrylate)
Crosslinking water soluble polymers
Conversion of hydrophobic polymers to hydrophilic
polymers plus crosslinking
Hydrogel Fabrication
+
Monomer Crosslinker
Vinyl group-containing water-soluble polymers
Copolymerization
Polymerization
Hydrogel network
Chemical crosslinking
• Polymerization of water soluble monomers in the presence of bi- or multifunctional cross-linking agent
EGDMA HEMA
An example as Wound Dressing
Ref.:
Based on ionic charges, hydrogels can be classified as...
Neutral hydrogels – No charge
Anionic hydrogels – Negatively charged
Cationic hydrogels – Positively charged
Ampholytic hydrogels – Capable of behaving either positively or negatively
Classes of Hydrogels
Hydrogel Forming Polymers
O H O
O H
H O 2 C
O O H O
N H
H O
O
O
O H O
O H
N a O 2 C
O
n p o l y ( h y a l u r o n i c a c i d ) p o l y ( s o d i u m a l g i n a t e )
n
O O
O
N H O n
poly ( e t h y l e n e g l y c o l )
n
p o l y ( l a c t i c a c i d )
n
p o l y ( N - i s o p r o p y l a c r y l a m i d e )
Natural
Synthetic
Hydrogel Swelling
One or more highly electronegative atoms which results in charge asymmetry favoring hydrogen bonding with water
Because of their hydrophilic nature dry materials absorb water
By definition, water must constitute at least 10% of the total weight (or volume) for a materials to be a hydrogel
When the content of water exceeds 95% of the total weight (or volume), the hydrogel is said to be superabsorbant
35
Important features of hydrogels
– Usually comprised of highly polyionic polymers
– Often exhibit large volumetric changes eg. highly compressed in secretory vesicle and expand rapidly and dramatically on release
– Can undergo volumetric phase transitions in response to ionic concentrations (Ca++, H+), temperature, ...
– Volume is determined by combination of attractive and repulsive forces:
repulsive electrostatic, hydrophobic
attractive, hydrogen binding, cross-linking
36
Swelling...Thermodynamically Speaking
Network starts to swell due to the thermodynamic compatibility of the polymer chains and water
– Swelling in chemical (crosslinked) polymers is dependent on the solvent
Swelling force is counterbalanced by the retractive force induced by the crosslinks of the network
Swelling equilibrium is reached when these two forces are equal
Degree of swelling can be quantified by:
• ratio of sample volume in the swollen state to volume in the dry state
• weight degree of swelling: ratio of the weight of swollen sample to that of the dry sample
Swelling Properties
Gibbs Free Energy � ∆G=∆Gelastic+∆Gmix
Chemical Potential
� µ1-µ1,0=∆µelastic+∆µmix
� ∆µmix=RT(ln(1-2v2,s)+v2,s+χ1v^22,s)
G=Gibbs Free Energy
– work exchanged by the system with its surroundings minus the work of the pressure forces during a reversible transformation of the system from the same initial state to the same final state
∆G<0 Spontaneous ∆G=0 Equilibrium ∆G>0 Non-spontaneous
Swelling Properties
Gibbs Free Energy � ∆G=∆Gelastic+∆Gmix
Chemical Potential
� µ1-µ1,0=∆µelastic+∆µmix
� ∆µmix=RT(ln(1-2v2,s)+v2,s+χ1v^22,s)
G=Gibbs Free Energy
– work exchanged by the system with its surroundings minus the work of the pressure forces during a reversible transformation of the system from the same initial state to the same final state
∆G<0 Spontaneous ∆G=0 Equilibrium ∆G>0 Non-spontaneous
µ= Chemical Potential ―the chemical potential is the change in a characteristic thermodynamic state function per change in the number of molecules ―Particles will tend to move from regions of high chemical potential to regions of low chemical potential
Swelling Properties
Gibbs Free Energy � ∆G=∆Gelastic+∆Gmix
Chemical Potential
� µ1-µ1,0=∆µelastic+∆µmix � ∆µmix=RT(ln(1-
2v2,s)+v2,s+χ1v^22,s)
v2,s=polymer volume fraction of the gel
v2,s= Volume of polymer = vp = 1 __________________ __ __ Volume of swollen gel vgel Q
Q= volume degree of swelling
χ1= polymer-water interaction
parameter (look up in a table)
R= Universal Gas Constant= 8.314 472(15) J K−1 mol−1
Some swollen Hydrogels Highly swollen hydrogels:
cellulose derivatives poly(vinyl alcohol) poly(ethylene glycol)
What do these all have in common? Lots of OH (or =O) groups to interact with acidic environments hydrophillic swelling Moderately or poorly swollen hydrogels:
poly(hydroxyethyl methacrylate), PHEMA and derivatives
One may copolymerize a highly hydrophilic monomer with other less hydrophilic monomers to achieve desired swelling properties
42
Contact Angle (wetability)
Hydrophobic – “water hating”
Hydrophilic – “water loving”
Why is this important to materials selection? – Do you want your eyes
to be dried out by your contact lenses? Probably not…
* Cool fact, fluorinated surfaces have the most hydrophobic properties and are deemed super-hydrophobic.
Electrowetting of the surface Top: charge neutral (grounded)
surface with high contact angle Bottom: Allowing voltage
between the drop and the electrode changes the distribution of electric charge within the drop and significantly decreases the contact angle. – The polarity of voltage in
the drawing is arbitrary, and in both directions electrowetting will occur.
In a natural environment, this may be electric charge change due to pH changes
Other Important Properties
Solute diffusion coefficient through the hydrogel
Optical properties
Mechanical properties – Hydrophilic hydrogel surfaces are poor
substrates for Protein adsorption Cell adsorption
How biological hydrogels grow
22-Apr-13 46
• Polymerization/deposition
(blood clots)
Environmentally Responsive Hydrogels
– Hydrogels that exhibit swelling changes due to the external
pH Temperature Ionic Concentration
Environmentally Responsive Hydrogels
pH
Location in Body pH
Gastric Contents 1.0
Urine 4.5-6.0
Intracellular 6.8
Interstitial (also called extravascular
compartment or tissue space) 7.0
Blood 7.15-7.35
Environmentally Responsive Hydrogels
Temperature
Location in Body Temperature °C
Normal Core 37
Deviations During Disease 20-42.5
Normal Skin 28
Skin at Extremeties 0-45
Environmentally Responsive Hydrogels
Ionic concentration
Cations Concentration in Blood (mEq/L)
Sodium 142
Pottasium 4
Calcium 5
Magnesium 2
Anions Concentration in Blood (mEq/L)
Chlorine 101
Bicarbonate 27
Phosphate 2
Sulfate 1
Proteins 22
Notice they both add up to the same…equillibrium
Hydrogel Advantages
– Non-thrombogenic
Non-ionic hydrogels used for blood contacting applications
Heparinized hydrogels show promise
– Biocompatible
– Good transport of nutrients to cells and products from cells
– May be easily modified with cell adhesion ligands
– Can be injected in vivo as a liquid that gels at body temperature
Advantages of Hydrogels Environment can protect cells and other substances (i.e.
drugs, proteins, and peptides) Timed release of growth factors and other nutrients to ensure
proper tissue growth Good transport properties Easy to modify
Disadvantages of Hydrogels
Low mechanical strength
Hard to handle
Difficult to load
difficult to be sterilized
Types of Hydrogels
Natural Polymers – Dextran, Chitosan, Collagen, Dextran Sulfate – Advantages Generally have high biocompatibility Intrinsic cellular interactions Biodegradable Cell controlled degradability Low toxicity byproducts
– Disadvantages Mechanical Strength Batch variation Animal derived materials may pass on viruses
Types of Hydrogels
Synthetic Polymers – PEG-PLA-PEG, Poly (vinyl alcohol) – Advantages Precise control and mass produced Can be tailored to give a wide range of properties (can be
designed to meet specific needs) Low immunogenecity Minimize risk of biological pathogens or contaminants
– Disadvantages Low biodegradability Can include toxic substances
Combination of natural and synthetic – Collagen-acrylate, P (PEG-co-peptides)
Properties of Hydrogels
Pore Size
Fabrication techniques
Shape and surface/volume ratio
H2O content
Strength
Swelling activation
Why Hydrogels?
Tissue Engineering – Scaffolds for tissue engineering
Cell Culture Systems
Drug Delivery – Time released delivery
Contact Lenses
Biomedical Uses for Hydrogels Common
– Scaffolds in tissue engineering. – Sustained-release delivery systems – Hydrogels that are responsive to specific molecules, such as
glucose or antigens can be used as biosensors. – Disposable diapers where they "capture" urine, or in sanitary
napkins – Contact lenses (silicone hydrogels, polyacrylamides) – Medical electrodes using hydrogels composed of cross linked
polymers (PEO, polyAMPS and polyvinylpyrrolidone) — Lubricating surface coating used with catheters, drainage tubes
and gloves
Biomedical Uses for Hydrogels Less common uses include
– Breast implants – Dressings for healing of burn or other hard-to-heal wounds.
Wound gels are excellent for helping to create or maintain a moist environment.
– Reservoirs in topical drug delivery; particularly ionic drugs – Artificial tendon and cartilage – Wound healing dressings (Vigilon®, Hydron®, Gelperm®)
non-antigenic, flexible wound cover permeable to water and metabolites
– Artificial kidney membranes – Artificial skin – Maxillofacial and sexual organ reconstruction materials – Vocal cord replacement – Butt injections
59
Headlines
Smart Polymers: Hydrogels and Shape
Memory Polymers Dr. Jenny Amos
February 19, 2009
Ref.:
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