5.Hydrogels

Question 1

Hydrogels

Answer 1

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

Question 2

Crosslinks or bonds of hydrogels

Answer 2

junctions connecting the polymer strands
permanent or reversible

Question 3

Gel-state

Answer 3

Solid, jelly-like materials, which exhibit no flow when in a steady state

Question 4

Properties of hydrogels

Answer 4

• 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

Question 5

Which propertie is the key in drug delivery systems?

Answer 5

Determine the exchange of nutrients, gasses, waste products and bioactive
agents

Question 6

Physical structure of hydrogels

Answer 6

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).

Question 7

Key parameters dictating the structure and properties of hydrogels

Answer 7

• Cross-linking density;
• Number of chemical or physical cross-links in a given volume;
• Distance between crosslinks (i.e., mesh size).

Question 8

Chemical composition

Answer 8

Charge
Hydrophilicity
Bioactivity

Question 9

Chemical composition determines

Answer 9

the biochemical properties of the hydrogel network

Question 10

Which parameters dictate structure-property relationship?

Answer 10

• 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

Question 11

Homopolymer hydrogels

Answer 11

• Cross-linked networks consisting of one type of hydrophilic monomer unit;

Question 12

Copolymer hydrogels

Answer 12

• Cross-linked networks composed of two comonomer units;

Question 13

Multipolymer hydrogels

Answer 13

• Cross-linked networks consisting of three or more comonomers;

Question 14

Interpenetrating network (IPN) hydrogels

Answer 14

• 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).

Question 15

Semi-IPN hydrogels

Answer 15

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.

Question 16

Characteristics of Traditional (single network) hydrogels

Answer 16

• Limited (weak) mechanics
• Static properties
• Inability to fully mimic key
  aspects of the cellular
  microenvironment

Question 17

Characteristics of SEMI-IPN hydrogels

Answer 17

• Mechanical reinforcement
• Rheological properties
• ‘Smart’ hydrogels => respond to external stimuli
• Tuneable cell-material interactions

Question 18

Periodate Oxidation

Answer 18

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

Question 19

Carbodiimide

Answer 19

Widely explored to functionalize carboxyl- or amine-containing polymers or to conjugate amine-containing peptides to polymers (e.g., alginate).

Question 20

Physically crosslinked hydrogels

Answer 20

Ionic interactions, pH and temperature changes, hydrogen bonds, protein interactions

Question 21

Chemically crosslinked hydrogels

Answer 21

Radical polymerization, (bioorthogonal) chemical reactions, energy irradiation, and enzymatic crosslinking

Question 22

Covalent crosslinking – general considerations

Answer 22

• 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!

Question 23

Covalent crosslinking: Free Radical Chain Polymerization

Answer 23

• 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.

Question 24

Covalent crosslinking: Tetrazine-norbornene reaction

Answer 24

Form irreversible covalent bonds upon mixing
rapid gelation

Question 25

Bioorthogonal Click Chemistry

Answer 25

§ Fast § High specificity à selective § Generate minimal byproducts

Question 26

Bioorthogonal Click Chemistry – Thiol-Michael type reaction

Answer 26

* Does not require radical initiators and can proceed under mild conditions (e.g., PBS, culture media).

Question 27

CLick reactions for hydrogel formation

Answer 27

CuAAC SPAAC Diels-Alder Inverse electron demand Diels-Alder Thiol-ene Michael addition Oxime

Question 28

Diels-Alder

Answer 28

-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

Question 29

Thiol-ene

Answer 29

-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

Question 30

Michael addition

Answer 30

Reacting functinoal groups: thiol and alfa,beta-unsaturated carbonyl group -no catalyst required -reversible **Application** -cell encapsulation an release -controlled cargo delivery

Question 31

How to control drug release form hydrogels?

Answer 31

* Mesh size (typically 5 to 100 nm) * Network degradation * Swelling degree * Drug-polymer interactions

Question 32

How to modulate mesh size?

Answer 32

* Polymer concentration * Crosslinker content * External stimuli (e.g., pH)

Question 33

pH-responsive hydrogels

Answer 33

* 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.