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HYDROGELS:
Introduction and Applications in
       Biology and Engineering
                            Jorge E. Roldan
                Louisiana Tech University
              Dept. of Biological Sciences
                              June 25, 2003
OVERVIEW
What are Hydrogels?
   Introduction
   Applications
   Types
   Properties
   Advantages and Disadvantages
Why Hydrogels?
   Tissue engineering
   Cell Culture Systems
   Drug delivery
   Scaffolds
Conclusion
What are Hydrogels?
Water-swollen, crosslinked polymeric structure
 produced by reactions of monomers or by
 hydrogen bonding

Hydrophilic polymers that can absorb up to
 thousands of times their dry weight in H2O

Three-dimensional insoluble polymer networks
Applications of Hydrogels
Soft contact lenses
Pills/capsules
Bioadhesive carriers
Implant coatings
Transdermal drug delivery
Electrophoresis gels
Wound healing
Chromatographic packaging material
Types of Hydrogels
Classification
  Method of preparation
    Homo-polymer, Copolymer, Multi-polymer,
     Interpenetrating polymeric

  Ionic charge
    Neutral, Catatonic, Anionic, Ampholytic


  Physical structure
    Amorphous, Semi-crystalline, Hydrogen-bonded
Types of Hydrogels
 Physical
   Polyanion + Multivalent Cation = “Iontropic” Hydrogels




 Chemical
   Polyanion + Polycation = Polyion Complex Hydrogels
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
Swelling properties influenced by
 changes in the environment
   pH, temperature, ionic strength, solvent
    composition, pressure, and electrical potential


Can be biodegradable, bioerodible, and
 bioabsorbable

Can degrade in controlled fashion
Properties of Hydrogels
Pore Size

Fabrication techniques

Shape and surface/volume ratio

H2O content

Strength

Swelling activation
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

 Biocompatible

 Can be injected

 Easy to modify
Disadvantages of Hydrogels
Low mechanical strength

Hard to handle

Difficult to load

Sterilization
Why Hydrogels?
Tissue Engineering
  Scaffolds for tissue engineering

Cell Culture Systems
  “In vivo conditions are not accurately mimicked
   in the majority of cell culture systems”

Drug Delivery
  Time released delivery
Why Hydrogels?: Background
Physiology
 Cell Phenotype
    The expression of a specific trait.
 Phenotype Regulation
    Environmental influences
       ECM determines adhesion factors, mechanical signals, and
         growth factors (i.e. CTGF, TGFβ, and Activin)
    Internal genetic programs
       Different combinations of receptors may cause differences in
         gene expression
 Cell Differentiation
    To become specialized
      Dependent on biochemical signals & ECM molecules
      Due to mechanical forces resulting from the spatial orientation
        cells grow in
Why Hydrogels?: Background
Physiology
An accurate understanding of the mechanisms
 by which cells interact with scaffold, is critical
 if one wishes to design and control cell
 phenotype and ultimate tissue structure (i.e.
 surface chemistry, 3-D space and tensional
 forces)
Why Hydrogels ?: Tissue
Engineering/Cell Culture Systems
Scaffold provides extracellular matrix:
  Cell adhesion sites
  Control of tissue form and thus function
  Diffusion of growth factors, metabolites, and
   nutrients
Build it, Shape it, and Seed it with
 cells and nutrients
Why Hydrogels ?: Tissue
Engineering
 Biocompatible
 H2O content
 Sterilizibilty
 Ease of use
 High mechanical
  Strength
 Surface to volume ratio
 Good cell adhesion
 High nutrient transport
Why Hydrogels?: Cell Culture
Systems
Biocompatible substrate
  Non-toxic and have no immunological
   responses
Cytoarchitecture which favors cell growth
  Flexibility for cells to rearrange in 3-D
   orientation
  Seeded with appropriate growth and adhesion
   factors
  Porosity (i.e. channels for nutrients to be
   delivered)
Why Hydrogels?: Cell Culture
Systems
Mimic cytomechanical situations
  3-D space provides balanced cytoskeleton
   forces
  Dynamic loading to promote cell growth
Flexibility
  Provide scaffold for various cells
Consistent, reproducible and easy to
 construct
Why Hydrogels?: Drug Delivery
Safe degradation products
Biocompatible
High loading with ensured molecule efficacy
High encapsulation
Variable release profile
Stable
Inexpensive
High quality
Conclusion
Hydrogels are network polymers that
 swell through a variety of mechanisms in
 an aqueous environment
Environment controls mechanisms of
 swelling:
  pH, ionic strength, solvent composition,
   pressure and even electric fields
Applications in medicine, engineering, and
 biology
Questions

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Hydrogels introduction and applications in biology and en

  • 1. HYDROGELS: Introduction and Applications in Biology and Engineering Jorge E. Roldan Louisiana Tech University Dept. of Biological Sciences June 25, 2003
  • 2. OVERVIEW What are Hydrogels?  Introduction  Applications  Types  Properties  Advantages and Disadvantages Why Hydrogels?  Tissue engineering  Cell Culture Systems  Drug delivery  Scaffolds Conclusion
  • 3. What are Hydrogels? Water-swollen, crosslinked polymeric structure produced by reactions of monomers or by hydrogen bonding Hydrophilic polymers that can absorb up to thousands of times their dry weight in H2O Three-dimensional insoluble polymer networks
  • 4. Applications of Hydrogels Soft contact lenses Pills/capsules Bioadhesive carriers Implant coatings Transdermal drug delivery Electrophoresis gels Wound healing Chromatographic packaging material
  • 5. Types of Hydrogels Classification Method of preparation Homo-polymer, Copolymer, Multi-polymer, Interpenetrating polymeric Ionic charge Neutral, Catatonic, Anionic, Ampholytic Physical structure Amorphous, Semi-crystalline, Hydrogen-bonded
  • 6. Types of Hydrogels  Physical  Polyanion + Multivalent Cation = “Iontropic” Hydrogels  Chemical  Polyanion + Polycation = Polyion Complex Hydrogels
  • 7. 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
  • 8. 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)
  • 9. Properties of Hydrogels Swelling properties influenced by changes in the environment  pH, temperature, ionic strength, solvent composition, pressure, and electrical potential Can be biodegradable, bioerodible, and bioabsorbable Can degrade in controlled fashion
  • 10. Properties of Hydrogels Pore Size Fabrication techniques Shape and surface/volume ratio H2O content Strength Swelling activation
  • 11. 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  Biocompatible  Can be injected  Easy to modify
  • 12. Disadvantages of Hydrogels Low mechanical strength Hard to handle Difficult to load Sterilization
  • 13. Why Hydrogels? Tissue Engineering Scaffolds for tissue engineering Cell Culture Systems “In vivo conditions are not accurately mimicked in the majority of cell culture systems” Drug Delivery Time released delivery
  • 14. Why Hydrogels?: Background Physiology  Cell Phenotype  The expression of a specific trait.  Phenotype Regulation  Environmental influences ECM determines adhesion factors, mechanical signals, and growth factors (i.e. CTGF, TGFβ, and Activin)  Internal genetic programs Different combinations of receptors may cause differences in gene expression  Cell Differentiation  To become specialized Dependent on biochemical signals & ECM molecules Due to mechanical forces resulting from the spatial orientation cells grow in
  • 15. Why Hydrogels?: Background Physiology An accurate understanding of the mechanisms by which cells interact with scaffold, is critical if one wishes to design and control cell phenotype and ultimate tissue structure (i.e. surface chemistry, 3-D space and tensional forces)
  • 16. Why Hydrogels ?: Tissue Engineering/Cell Culture Systems Scaffold provides extracellular matrix: Cell adhesion sites Control of tissue form and thus function Diffusion of growth factors, metabolites, and nutrients Build it, Shape it, and Seed it with cells and nutrients
  • 17. Why Hydrogels ?: Tissue Engineering  Biocompatible  H2O content  Sterilizibilty  Ease of use  High mechanical Strength  Surface to volume ratio  Good cell adhesion  High nutrient transport
  • 18. Why Hydrogels?: Cell Culture Systems Biocompatible substrate Non-toxic and have no immunological responses Cytoarchitecture which favors cell growth Flexibility for cells to rearrange in 3-D orientation Seeded with appropriate growth and adhesion factors Porosity (i.e. channels for nutrients to be delivered)
  • 19. Why Hydrogels?: Cell Culture Systems Mimic cytomechanical situations 3-D space provides balanced cytoskeleton forces Dynamic loading to promote cell growth Flexibility Provide scaffold for various cells Consistent, reproducible and easy to construct
  • 20. Why Hydrogels?: Drug Delivery Safe degradation products Biocompatible High loading with ensured molecule efficacy High encapsulation Variable release profile Stable Inexpensive High quality
  • 21. Conclusion Hydrogels are network polymers that swell through a variety of mechanisms in an aqueous environment Environment controls mechanisms of swelling: pH, ionic strength, solvent composition, pressure and even electric fields Applications in medicine, engineering, and biology