1. Hydrogels and Their Biomedical Uses

2. Overview
Hydrogels
Structure
Swelling properties
Biomedical Uses

3. 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

5. Applications of Hydrogels
Soft contact lenses
Pills/capsules
Bioadhesive carriers
Implant coatings
Transdermal drug delivery
Electrophoresis gels
Wound healing
Chromatographic packaging material

6. 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)

7. 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

8. 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).

9. Q = actual sample volume in the swollen state
Volume degree of swelling (Q)
Q = actual sample volume in the swollen state
volume in the dry state

10. = actual sample weight in the swollen state
Weight degree of swelling
= actual sample weight in the swollen state
weight in the dry state

11. 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

12. Based on crosslinkers features, hydrogels can be classified as...
Chemical
Physical

13. 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)

14. Non-covalently crosslinked
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)

15. Hydrogel Fabrication Chemical hydrogels Physical hydrogels
Covalently crosslinked
Noncovalently crosslinked
▪ Hydrogen bonding
▪ hydrophobic interaction
▪ crystallinity
▪ stereocomplex formation
▪ ionic complexation
Thermoset hydrogels
Thermoplastic hydrogels
Reliable shape stability and memory
Limited shape stability and memory

17. Physical crosslinking
Cross-linking without chemical reaction
ionic interaction, hydrogen bonding, antigen-antibody interaction, supramolecular association
• Ionic hydrogel

20. 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

21. Chemical crosslinking
Hydrogel Fabrication
Chemical crosslinking
Polymerization of water soluble monomers in the presence
of bi- or multifunctional cross-linking agent +
Monomer
Crosslinker
Vinyl group-containing water-soluble polymers
Copolymerization
Polymerization
Hydrogel network

22. EGDMA
HEMA

26. An example as Wound Dressing

29. Ref.:

30. poly(acrylic acid) (PAAc)

31. 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

32. Classes of Hydrogels

33. Hydrogel Forming Polymers
Natural O H 2 C N a n p o l y ( h u r i c d ) s m g t e
Synthetic O N H n p o l y ( e t h g c ) a i d - s r m

35. 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

36. 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
Secretory غده‌ مترشحه‌

37. 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

38. Swelling Properties Gibbs Free Energy Chemical Potential
DG=DGelastic+DGmix
Chemical Potential
m1-m1,0=Dmelastic+Dmmix
Dmmix=RT(ln(1-2v2,s)+v2,s+c1v^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
DG<0 Spontaneous
DG=0 Equilibrium
DG>0 Non-spontaneous

39. Swelling Properties Gibbs Free Energy Chemical Potential
DG=DGelastic+DGmix
Chemical Potential
m1-m1,0=Dmelastic+Dmmix
Dmmix=RT(ln(1-2v2,s)+v2,s+c1v^22,s)
m= 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
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
DG<0 Spontaneous
DG=0 Equilibrium
DG>0 Non-spontaneous
Electrophoresis: For example, consider charged particles in a fluid. A concentration gradient in a fluid may promote movement of particles in one direction, and the electric potential gradient may promote movement of the particles in another. The chemical potential would account for both concentration and electric components and describe a potential distribution that determines net particle movement.
In hydrogels: accounts for water on outside and inside of polymer network, can be altered by heat formed during mixing and entropy changes during mixing

40. Swelling Properties Gibbs Free Energy DG=DGelastic+DGmix
Chemical Potential
m1-m1,0=Dmelastic+Dmmix
Dmmix=RT(ln(1-2v2,s)+v2,s+c1v^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
c1= polymer-water interaction parameter
(look up in a table)
R= Universal Gas Constant=  472(15) J K−1 mol−1

41. 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.

43. 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

44. Other Important Properties
Solute diffusion coefficient through the hydrogel
Optical properties
Mechanical properties
Hydrophilic hydrogel surfaces are poor substrates for
Protein adsorption
Cell adsorption

45. How biological hydrogels grow
Polymerization/deposition
(blood clots)
12/2/2019

46. Environmentally Responsive Hydrogels
Hydrogels that exhibit swelling changes due to the external pH
Temperature
Ionic Concentration

47. Environmentally Responsive HydrogelspH
Location in Body pH
Gastric Contents
1.0
Urine
Intracellular
6.8
Interstitial
(also called extravascular compartment or tissue space)
7.0
Blood

48. Environmentally Responsive Hydrogels
Temperature
Location in Body
Temperature °C
Normal Core 37
Deviations During Disease
Normal Skin 28
Skin at Extremeties
0-45

49. 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

50. 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
Thrombogenic لخته زا

51. 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

52. Disadvantages of Hydrogels
Low mechanical strength
Hard to handle
Difficult to load
difficult to be sterilized

53. 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
intrinsic
ذاتي‌، اصلي‌، باطني‌، طبيعي‌، ذهني‌، روحي‌، حقيقي‌، مرتب‌، شايسته‌

54. 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)

55. Properties of Hydrogels
Pore Size
Fabrication techniques
Shape and surface/volume ratio
H2O content
Strength
Swelling activation

56. Why Hydrogels? Tissue Engineering Scaffolds for tissue engineering
Cell Culture Systems
Drug Delivery
Time released delivery
Contact Lenses

57. 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
Hydrogels are non-adherent and can be removed without trauma to the wound.
Slough sich häuten (Tiere); sich ablösen; abwerfen (Haut); aufgeben
Diaper پارچه‌ء‌ قنداق‌، گل‌ و بوته‌داركردن‌، گل‌ و بوته‌ كشيدن‌،كهنه‌ء‌ بچه‌ را عوض‌ كردن‌
PolyAMPS, or poly(2-acrylamido-2-methyl-1-propanesulfonic acid), is an organic polymer. It is water-soluble, forms gels when cross linked, and acts as an anionic polyelectrolyte. It can be used for ion exchange resins. It can form hydrogels.

58. 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
Kidney کليه
Butt مقعد

59. Headlines

60. Smart Polymers: Hydrogels and Shape Memory Polymers
Ref.:
Smart Polymers: Hydrogels and Shape Memory Polymers
Dr. Jenny Amos
February 19, 2009