Lecture 2 - Hydrogel Processing

Question 1

Hydrogel

Answer 1

• Highly hydrate polymer network
• Insoluble in water
• Water content > 30%
• Swell substantially in aqueous conditions to equilibrium condition where mass fraction of water much higher than that of polymer

Question 2

Hydrogel Backbone

Answer 2

• Hydrophilic
• Poly(ethylene glycol) —> (CH2-CH2-O)n
• Polyamide-like protein

Question 3

Hydrogel Side Groups

Answer 3

• Hydrophilic
• Hydroxyl —> (-OH)
• Carboxyl —> (-COOH)
• Amide —> (-CONH2)
• Sulfonic —> (-SO3H)

Question 4

Hydrogel Polymer Chains

Answer 4

Either chemically or physically crosslinked

Question 5

Advantages of Hydrogels as Tissue Engineering Matrices

Answer 5

• Aqueous environment for cells
• Porous to allow for nutrient transport
• Easily modified
• Usually biocompatible

Question 6

Disadvantages of Hydrogels as Tissue Engineering Matrices

Answer 6

• Hard to handle
• Physically weak
• Difficult to sterilize

Question 7

Chemical Advantages of Hydrogels as Tissue Engineering Matrices

Answer 7

• Crosslinked polymer network
• Polymer chains connected by covalent bonds to form network
• Monomer + crosslinker –copolymerize–> hydrogel network
• Macromers –copolymerize or crosslink macromers–> hydrogel network
• Water soluble polymer –crosslink polymer–> hydrogel network

Question 8

Chemical Hydrogels by Polymerization

Answer 8

• Polymerization of monofunctional vinyl monomers with difunctional vinyl monomers (act as crosslinkers)
• Acrylic acid, methacrylic acid, metacrylamide, hydroxyethyl methacrylate

Question 9

Biodegradable Hydrogels

Answer 9

• Necessary for tissue engineering applications
• Biodegradable crosslinkers often introduced
• Biodegradable after introduction of degradable PLA, PGA, PLGA et al.

Question 10

Photopolymerization

Answer 10

• Polymerization under UV light
• Includes light-induced initiation (excitation of a photoinitiator or PI) and subsequent polymerization
• Biocompatible photoinitiator is needed

Question 11

Physical Hydrogel

Answer 11

• Continuous, three-dimensional networks formed by associative force capable of forming non-covalent crosslinks
• Non-covalent crosslinks formed by weaker interactions (hydrogen bond, ionic interaction, hydrophobic association) and are reversible
• Produced without chemical reaction, more suitable for cell and biomolecules encapsulation since it avoids use of toxic chemicals

Question 12

Hydrophobic Interactions

Answer 12

• Amphiphilic polymers can self-assemble by aggregation of hydrophobic moieties among each other to form hydrogel
• Mixed hydrophilic polar group (-CONH-) and hydrophobic non-polar group [-CH(CH3)2]
• When T<32C, homogenous solution
• When T>32C, polymer solution starts to dehydrate and aggregates to form hydrogels

Question 13

Ionic Interactions

Answer 13

• Hydrogel formed by ionic interaction (cationic and anionic)
• Ex: Alginate. Alginates contain carboxylic groups, undergo reversible gelation in aqueous solution through interaction with divalent-cations such as Ca2+. Cations bind between G-blocks of adjacent alginate chains creating ionic inter-chain bridges. Forms three-dimensional network of alginate fibers (hydrogel)

Question 14

Hydrogen Bond Interactions

Answer 14

• Occur between proton donor (carboxyl -COOH and hydroxy -OH) groups and proton acceptor (O, N) groups. Polymers bearing these groups may form gels due to hydrogen bonds

Question 15

Collagen Gel

Answer 15

• Collagen dissolved in acid solution and then neutralized, becomes insoluble gel (not water soluble). This allows to incorporate cells and biomolecules in collagen gel.

Question 16

Water Content

Answer 16

• Water content = (m_HG,w - m_HG,d)/m_HG,d x 100% where m_HG,w and m_HG,d are wet and dry HG weights
• If hydrogel has 100% water absorption, m_HG,w = 2 x m_HG, d

Question 17

Hydrogel Mechanical Properties

Answer 17

• Depend on polymer/crosslinker characteristics, water content
• Polymer content: increase of polymer content in hydrogel increases mechanical properties
• Crosslinking density: increase in crosslinking density increases mechanical properties
• Water content: increase of water content decreases mechanical properties

Question 18

Hydrogel Degradation

Answer 18

• Hydrolysis
• Enzymatic degradation
• Dissolution

Question 19

Hydrolysis

Answer 19

• Most synthetic hydrogels degraded by hydrolysis of ester linkages

Question 20

Enzymatic Degradation

Answer 20

• Natural polymers such as collagen, chitosan are degraded by enzymes
• Enzyme (collagenase) breaks down peptide bond in collagen

Question 21

Dissolution

Answer 21

• Ionically crosslinked alginate undergoes dissolution, where rate depends on pH
• Decreased pH, increased degradation

Question 22

Natural Hydrogels

Answer 22

• Most closely resemble tissues meant to replace
• Almost always biocompatible
• Biodegradable
• Difficult to isolate from biological tissues
• Restricted versatility

Question 23

Synthetic Hydrogels

Answer 23

• Can be reliably produces
• Greater control over polymer structure
• May not be biocompatible
• Not always biodegradable
• Use of toxic reagents