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Hydrogels (Natural Materials (Fibrin (Contains important cell signalling…
Hydrogels
Natural Materials
Fibrin
Formed by interaction of thrombin and fibrinogen
Used clinically as a sealant (induces clotting)
Contains important cell signalling molecules
Cell proliferation
Cell migration
Difficult to polymerize
Forms fragile gels
Collagen
High tensile strength
Controllable resorbability
Easily denatured
Used in meniscal tissue engineering
Type 1 collagen used as a scaffold
Meniscal bovine fibrochondrocytes mixed in
Cells rearrange collagen fibres to resemble menisci
Alginate
Derived from brown seaweed
Widely used in food and pharmaceuticals
Binds divalent cations
Forms shape-stable hydrogels
Gentle gelation mechanisms
Decellularized ECM
Remove celllular material using enzymes
Minced ECM can be injected
Forms hydrogel in body
Advantages
Recognition and degradation by the body
Binding of biomolecules
Chemical modification allows tailorability
Disadvantages
Immunogenicity
Synhesis challenges
batch-batch variability
Hyaluronic Acid
Chief component of ECM
Connective tissue
Neuronal tissue
Glial tissue
Functions
Cell migration
Cell proliferation
Wound healing
High negative charge
Attracts water and ions
Regulates water content in tissues
Chemical modification
Methacrylate (UV reactive)
Hydroside (reacts with aldehyde groups)
Incorporate biomolecules
Promote differentiation of encapsulated cells
Synthetic Materials
Synthetic mimics of natural materials
Collagen-mimetic peptides
Short collagen mimetic chains
Natural collagen is difficult to use
Self-assemble -> collagen-like fibrils
Degradation properties similar to collagen
Recombinant bacterial collagen
Engineered to add linkers
Incorporation of bioactive peptides
Cross links can be degraded by entrapped cells
Self-assembling peptide amiphiles
Hydrophillic and hydrophobic components
Form micelles in water
Nanorods
Stable gels
Scaffolds
May be injectable
PEG
Easy to modify for hydrogel formation
Multi-arm PEGs -> varying mechanical properties
Cells can be encapsulated
Strongly hydrophillic
Protein resistance
Antifouling
Biocompatible
P(NIPAAm)
Exhibits reversible phase transition
Greater than 32 degrees, Soluble->insoluble
Can be adjusted (+ hydrophillic/hydrophobic groups)
Injectable
Gelation increases above 37 degrees
Cell sheet engineering
Culture cells on P(NIPAAm)
Lower temp causes sheet to peel off
Layers can be used as a patch
Maintains properties (e.g. cardiomyocytes beat)
P(HEMA)
Soft contact lenses
Can be moulded and cross linked to set chape
Incorporate molecules to promote
differentiation of encapsulated cells
Advantages
Tailorable for preferred properties
Reproducible
Smart polymers can be designed
Disadvantages
Toxicity -> chronic inflammation
Poor clearance of degradation products
General
Properties
High water content
Biocompatible
Good diffusion properties
Shear-thinning
Potentially injectable
Minimally-invasive
Cross-linking density
Reduces mesh size
Reduces swelling
Increases stiffness
Cell differentiation
Reduces mass transport (diffusion)
Reduces porosity
Increases degradation time
Bioactivity
Incorporation of biomolecules
Match to tissue of interest
Engineering Dynamic Properties
Cell-mediated degradation
Peptide cross-links can be cleaved by MMPs
Rate can be controlled
Biologically relevant rates
Light-controlled bioactivity
Cleavage of cross-links
Specific wavelength of light
Allows release of a specific biomolecule
Independent release of molecules
Spatial degradation can be controlled
Photopatterning
Photodegradation
Forms microfluidic channels
Stiffness/chemical gradients
Mimics anisotropic materials
Vary crosslinking density with depth
Different biomolecules can be incorporated into each layer
Tissues ~ cartilage
3D bioprinting
Shear-thinning hydrogels can be printed
Cells can be embedded in the printed hydrogel
Enables fabrication of complex structure
Classes
Physically cross-linked
Reversible
pH
Temperature
Stress
Concentration of solutes
Molecular entanglements
Secondary forces
Ionic bonds
Hydrogen bonds
Hydrophobic interactions
Covalently cross-linked
Irreversible
Addition of chemical cross-linkers
Irradiation
Reacting functional groups
Definition
Insoluble network of hydrophillic polymer chains
Can absorb extremely large amounts of water compared to their mass
solid-like properties
Hybrid Networks
Alginate + Polyacrylamide
Super stretchy
Non-covalent bonds can break and reform
Covalent bonds maintain structure
PEG + Hyaluronic Acid
Photocrosslinkable
In-situ curing
PEG:HA ratio allows tuning of elastic modulus
Injectable
Implant volume can be reduce by enzymatic degradation