5.Hydrogels Flashcards
Hydrogels
A physically or chemically crosslinked polymer swollen in water
(or biological fluids)” that can contain large amounts of water, up to
thousands of times their dry weight
Crosslinks or bonds of hydrogels
junctions connecting the polymer strands
permanent or reversible
Gel-state
Solid, jelly-like materials, which exhibit no flow when in a steady state
Properties of hydrogels
- Hydrophilic properties => high-water content
- High biocompatibility (but depends on the hydrogel properties!)
- Typically soft and elastic => hermodynamic compatibility with water
- Smooth and rubbery nature => viscoelasticity
- Porosity => solute transport
- Recapitulate key aspects of the native tissues
- Easy processing
- Tunable physical, chemical and biological properties
- Amenable to chemical functionalization
- Can be produced under cytocompatible conditions => cell encapsulation
Which propertie is the key in drug delivery systems?
Determine the exchange of nutrients, gasses, waste products and bioactive
agents
Physical structure of hydrogels
Characterized by junctions or tie points, which can be formed by from physical entanglements, microcrystallite formation and weak interactions (e.g., hydrogen bonds) or strong chemical linkages (e.g., covalent bonds).
Key parameters dictating the structure and properties of hydrogels
- Cross-linking density;
- Number of chemical or physical cross-links in a given volume;
- Distance between crosslinks (i.e., mesh size).
Chemical composition
Charge
Hydrophilicity
Bioactivity
Chemical composition determines
the biochemical properties of the hydrogel network
Which parameters dictate structure-property relationship?
- Source
- Polymer composition/chemical nature of the polymer backbone
- Chemistry of functional groups
- Type and nature of the cross-links
- Electrical charge
- Water-swelling behavior
Homopolymer hydrogels
- Cross-linked networks consisting of one type of hydrophilic monomer unit;
Copolymer hydrogels
- Cross-linked networks composed of two comonomer units;
Multipolymer hydrogels
- Cross-linked networks consisting of three or more comonomers;
Interpenetrating network (IPN) hydrogels
- Cross-linked networks made of at least two independently cross-linked synthetic and/or natural polymer components
- formed by the combination of two or more interlocked crosslinked polymer chains, which are mutually independent and held together by internetwork entanglement (without chemical bonds between the polymers).
Semi-IPN hydrogels
formed by the combination of two or more interlocked crosslinked polymer chains, in which one component presents a cross-linked structure, while the other(s) remains as a non-crosslinked polymer.
Characteristics of Traditional (single network) hydrogels
- Limited (weak) mechanics
- Static properties
- Inability to fully mimic key
aspects of the cellular
microenvironment
Characteristics of SEMI-IPN hydrogels
- Mechanical reinforcement
- Rheological properties
- ‘Smart’ hydrogels => respond to external stimuli
- Tuneable cell-material interactions
Periodate Oxidation
Oxidation of –OH groups to generate aldehydes, which can used for chemical crosslinking via Schiff base reaction or to improve the degradation of polymers.
Alteration of the conformation of urinate residues to an open-chain
adduct
Susceptible to hydrolysis
Carbodiimide
Widely explored to functionalize carboxyl- or amine-containing polymers or to conjugate amine-containing peptides to polymers (e.g., alginate).
Physically crosslinked hydrogels
Ionic interactions, pH and temperature changes, hydrogen bonds, protein interactions
Chemically crosslinked hydrogels
Radical polymerization, (bioorthogonal) chemical reactions, energy irradiation, and enzymatic crosslinking
Covalent crosslinking – general considerations
- Hydrogels formed by the establishment of covalent bonds
- Catalysts or initiators are usually required for bond formation => potential
cytotoxicity; - Can remain stable for long time periods, BUT depends on the susceptibility to
degradation of the hydrogel network
e.g., hydrolysis!
Covalent crosslinking: Free Radical Chain Polymerization
- Three steps: (1) initiation, (2) propagation, and (3) termination;
- Water-soluble (photo)initiator
- Formation of reactive free radicals => can cause damage to cell membranes!!
- Functional groups are introduced into the polymer backbone to allow hydrogel
formation.
Covalent crosslinking: Tetrazine-norbornene reaction
Form irreversible covalent bonds upon mixing
rapid gelation
Bioorthogonal Click Chemistry
§ Fast
§ High specificity à selective
§ Generate minimal byproducts
Bioorthogonal Click Chemistry – Thiol-Michael type reaction
- Does not require radical initiators and can proceed under mild conditions (e.g.,
PBS, culture media).
CLick reactions for hydrogel formation
CuAAC
SPAAC
Diels-Alder
Inverse electron demand Diels-Alder
Thiol-ene
Michael addition
Oxime
Diels-Alder
-Reacting functional groups: Conjugated diene and substituted alkene
-no catalyst required
-longer reaction time than most of the other click reaction
Application
-cell encapsulation an release
-controlled cargo delivery
Thiol-ene
-Reacting functional groups: thiol and unsaturated functional group
-spatiotemporal control possible with select chemistries and using a photoinitiator
Application
-cell encapsulation
-degradable 3D cell culture
Michael addition
Reacting functinoal groups: thiol and alfa,beta-unsaturated carbonyl group
-no catalyst required
-reversible
Application
-cell encapsulation an release
-controlled cargo delivery
How to control drug release form hydrogels?
- Mesh size (typically 5 to 100 nm)
- Network degradation
- Swelling degree
- Drug-polymer interactions
How to modulate mesh size?
- Polymer concentration
- Crosslinker content
- External stimuli (e.g., pH)
pH-responsive hydrogels
- Undergo physical changes (swelling/shrinking) as a result of pH variations in the surrounding environment;
- Characteristic of polymers with with ionizable functional groups;
- Ability to release drugs at a specific pH.
