BENG 186A Lecture 5: Hydrogels and Natural Materials

What are the special classes of polymers?

• Hydrogels - 3D network of water absorbing polymers

• Natural polymers - large molecules produced by living organisms

What are hydrogels?

Water swollen, insoluble polymer networks that can be swollen up to thousands of times their dry weight

What are hydrogel applications in medicine?

• Pills/capsules

• Bio-adhesive carriers

• Implant coatings

• Transdermal drug delivery

• Wound healing

• Tissue engineered scaffolds

• Soft contact lenses

What are the types of hydrogels?

• Homopolymer hydrogels – crosslinked networks of one type of

hydrophilic monomer

• Copolymer hydrogel – crosslinked chains of two co-monomer

units (at least one must be hydrophilic)

• Multi-polymer hydrogels – three or more co-monomers

• Interpenetrating hydrogels – multiple networks that are entangled

What are the charge characteristics of hydrogels?

• Neutral - swelling is less sensitive to pH

• Anioinc - swell more at higher pH

• Cationic - swell more at lower pH

What is hydrogel structure like?

• Can be amorphous – random

  arrangement, held together with

  covalent linkages

• Can be semi-crystalline – ordered

  structure, may or may not have

  covalent linkages

• Rare to have “ideal” networks

What are the interactions that keep hydrogels together?

• Covalently crosslinked gels

• Physical entanglement

• Physically crosslinked gels

• Hydrogen bonding

• Ionic forces

• Affinity interactions

• Hydrophobic interactions

• Polymer crystalline domains

What are covalently linked hydrogel crosslinking strategies?

• Chemical

• Ionizing radiation

What are affinity based hydrogels?

• Affinity complexes: coiled-coil peptide interactions, biotin and steptavidin, anitbody, cyclodextrin inclusion complexes

What are hydrophilic and hydrophobic interactions?

• Hydrophilic are collagen like triple helices

• Hydrophobic - self organize through physical crosslinks

What are polymer interactions with water?

• Hydrophilic - polar and ionic side chains have high interactions with water

• Hydrophobic - non polar neutral side chains do not interact with water, and water must organize around hydrophobic domains leading to decrease in entropy

• Crystalline materials are resistant to hydration due to physical exclusion of water

What affects hydrogel swelling?

• Chemical composition of hydrogel and solvent

• Length of crosslinker and density of crossliner

• Changes in environment: pH, temperature, ionic strength, solvent composition, pressure, and electric properties

Why is hydrogel swelling important?

• Swelling affect solute diffusion coefficient through the gel

• Surface properties

• Optical properties

• Mechanical properties

• Degree of swelling can be described by volume and weight

What are smart hydrogels?

• Drastic changes in swelling ratios based on environmental cues: pH, temperature, ionic strength, enzymatic or chemical reaction, mechanical stimulus

• Most responsive hydrogels have a critical point where a sharp transition occurs

• Reversible

What are advantages of hydrogels?

• Environment can protect cells and other substances

• Can be used for drug delivery

• Likely to be biocompatible

• Can potentially be injected

• Easily modified

Disadvantages of hydrogels?

• Low mechanical strength

• Difficult to handle

• Difficult to sterilize

• Difficult to load payloads

What are other natural polymers?

Other natural polymers are constituents of the extracellular matrix

What are the major components of the extracellular matrix?

• Collagen

• Fibronectin

• Laminin

• Proteoglycans

What is collagen, what is its use?

• Type I

• Cells can adhere to collagen

• Can signal in cells and change behavior

• Cells can shrink collagen

• Poor mechanical strength

• Low forces from cells, moderate forces across tissue, and high forces rupture of intrafibril crosslinks

What is gelatin?

• Denaturation of collagen

• Forms gels, microspheres and sponges

• Excellent for cell attachement

• Poor mechanical strength

What is fibrin glue?

• Formed by enzymatic polymerization of fibrinogen

• Used as surgical sealant

• Promotes local tissue growth and repair

• Degrades rapidly, around two weeks

What is hyaluronic acid?

• GAG with no protein

• Highly negatively charged

• Not antigenic, no inflammatory response or foreign body reaction

• Poor cell adhesion

• Poor mechanical properties by itself

• Fast degradation

• Physical entanglements or chemical crosslinking

What is decellularized ECM?

• Natural polymers that have a native 3D achitecture and complex composition

• Multiple types of polymers

• Growth factors

How does the high hydration state of GAGs behave with and without compression?

Where in the body is this useful?

• Without compression – GAGs absorb and retain large amounts of water, the tissue is

swollen and resilient and provides cushioning and allows nutrients and waste

products to diffuse through

• With compression – water is squeezed out of matrix, tissue resists compression due

to fluid pressure and osmotic forces and when load is removed water flows back in

• This behavior is important in articular cartilage (joints), intervertebral discs, synovial

fluid, skin and connective tissue, vitreous humor of eye

Name a pro and a con of naturally derived polymers.

• Pros – biocompatible, biodegradable, bioactive, mimic natural ECM, hydrophilic,

renewable and sustainable, can be chemically modified

• Cons – poor mechanical strength, variable properties, rapid degradation, difficult

processing, potential immunogenicity, risk of pathogen transmission, limited shelf

life, higher cost

Name a pro and a con of synthetically derived polymers.

• Pros – tailorable properties, high mechanical strength, reproducible properties, good

  processability, controlled degradation, low risk immune response, long shelf life,

  large range of properties

• Cons – lower bioactivity, poor biocompatibility, less similar to natural tissues,

  degradation products may be harmful, limited cell recognition, non-renewable

  sources, may require surface modification

According the Flory-Huggins theory, why do polymers have a lower entropy of mixing

compared with small molecules?

Polymer chains occupy many lattice sites, reducing number of possible

arrangements. Polymer chain is made of many connected repeating units and occupies multiple lattice sites in a mixture, greatly limiting the number of possible configurations

compared with small molecules, reducing entropy gain upon mixing