Lecture 24 - Biofouling

Question 1

Biofouling

Answer 1

• Accumulation of biological materials or other materials that are wetted
• For biomedical materials, build-up of protein or micro-organisms that interferes with functions

Question 2

Biofilm Formation

Answer 2

• Attachment, colonization, growth

Question 3

Protein Adsorption

Answer 3

• Adsorption of proteins and biomolecules
• Stimulation of neutrophils in response to inflammation signals
• Substitution of monocytes & macrophages
• Inflammatory and regenerative responses
• Multinucleated foreign body giant cells
• Thick collagenous fibrous capsule around implant

Question 4

Situations Where Troublesome for Biomedical Materials

Answer 4

• Don’t want fibrous encapsulation
• No protein adsorption (occlusion)
• Bacterial colonization
• Corrosion
• Excessive protein deposition can alter diffusivity out of device and encourage significant fibrous encapsulation (drug delivery devices and immunoisolation devices)
• Excessive protein deposition or cell adhesion can prevent biomedical implants from sensing

Question 5

Biofouling: Corrosion

Answer 5

• Microorganisms on implant surfaces can alter microenvironment and promote corrosion
• Bacteria can produce hydrogen sulfide (corrodes material, induce stress cracking in metals)
• Bacteria directly oxidizes the material
• Bacteria can form wide array of different acid that speed corrosion
• Can corrode polymers —> cause cracking and other mechanical damage and breakdown of materials

Question 6

Methods for Biofouling Prevention

Answer 6

Must consider protein adsorption:

• Protein doesn’t absorb to surface and stays dissolved
• Protein adsorbs reversibly to surface
• Protein adsorbs irreversibly to surface with conformational changes
• Total change in free energy of system determines which option (factors include properties of protein, surface, solution material is in)

Question 7

Surface - Protein Interaction

Answer 7

• Hydrophobic surfaces

- Hydrophilic surfaces

Question 8

Hydrophobic Surfaces

Answer 8

• Adsorption largely driven by entropy gain
• Water molecules no longer need to be in contact with the surface and can arrange in more energetically favorable manner
• Rearrangement within protein structure also promotes adsorption (globular protein may have tightly packed hydrophobic core surrounded by hydrophilic polar amino acids) —> core might be less organized upon adsorption and entropy gained, denaturation process normally leads to irreversible binding

Question 9

Hydrophilic Surfaces

Answer 9

• No entropy gain by displacing water (already in favorable order on the surface)
• Adsorption is dictated by electrostatics and hydrogen bonding between polar protein “shell” and surface
• Most protein/surface combinations tend to lead to irreversible adsorption (strong binding)
• Reversible adsorption may take place, if relative balance between attractive and repulsive interactions
• No binding —> electrostatic repulsion between a charged and rigid protein and hydrophilic surface with same magnitude but opposite charge

Question 10

Ideal Anti-Biofouling Implant

Answer 10

• Synthetic material which can prevent adsorption of all proteins yet to be discovered
• Many materials and chemical treatments can provide low protein binding
• In general, materials should be electrostatic neutral, functional groups with hydrogen bond acceptors but not donors, and hydrophilic

Question 11

Materials for Anti-Biofouling

Answer 11

• Polyethylene glycol (PEG)

- Zwitterionic Materials

Question 12

Polyethylene glycol (PEG)

Answer 12

• Water soluble polymer with unique properties —> very low protein adsorption when grafted to a surface, low toxicity
• Coating properties control protein adsorption —> chain length (longer chains, higher resistance), chain density (too low means adsorption in between chains, too high means adsorption on top of chains)

Question 13

Polyethylene glycol (PEG): Steric Repulsion

Answer 13

Adsorption of protein results in energetically unfavorable compression of PEG

Question 14

Polyethylene glycol (PEG): Chemistry

Answer 14

• No formal electrostatic charge (no electrostatic attraction to protein)
• Polar and interact strongly with surrounding water molecules

Question 15

Polyethylene glycol (PEG): Coating

Answer 15

• Chain length (longer chains, higher resistance)

- Chain density (too low means adsorption in between chains, too high means adsorption on top of chains)

Question 16

Issues of PEG Coatings

Answer 16

• Poor stability (oxide degradation, many bacteria can metabolize PEG - alcohol dehydrogenase enzymes)
• Coatings susceptible to fail when duration of use is long

Question 17

Zwitterionic Materials

Answer 17

• Have formal positive and negative charges but are net neutral
• Many amino acids are zwitterionic at appropriate pH (when carboxylic acid and amine are in charged state)
• Results in no electrostatic attraction of proteins