Quiz 4: Anti-infective Coating & Infection Prevention Flashcards
high infection rate from devices is due to
direct exposure to bodily fluids and invasive placement within the body
control of biofilm formation: Antimicrobial approaches
Most biomaterials in this category either display or release bioactive molecules, while others promote cell lysis by exposing functional groups that effectively interact with bacteria cell membranes. (Intrinsically bioactive biomaterials: Cationic materials)
Biomaterials releasing bioactive molecules
Surface modification with antibacterial agents:
- Antibiotics
- Metal ions
- Nitric oxide
Different strategies to apply bioactive molecules to biomaterial surface:
- Physical adsorption (simplest strategy: surface)
- Impregnation inside the biomaterial (bulk, e.g., pores)
- Complexation
- Conjugation
Antibiotics
Examples in orthopedic applications:
- Gentamicin (most common)
- Gentamicin + Vancomycin
Antibiotics-loaded (A-L) bone cement (bone cement impregnation)
Coating implant surfaces with biodegradable materials that release antibiotics in a controlled fashion.
- PLGA or PLA polymer as coatings for Titanium (Ti) implants to deliver gentamicin.
- Mesoporous hydroxyapatite, combined with antibiotics as coatings for dental and bone implants.
Silver
Silver (Ag+) accumulates at the cellular membrane and leads to membrane perforation. Also, Ag+ promotes the generation of reactive oxygen species.
- Formulations include Ag salts, Ag oxide, metallic Ag, Ag alloy, or Ag nanoparticles (the most active form).
- Silver has been loaded in PLGA coating for Ti implants; commonly used in urinary catheters; successfully used in wound-dressing materials.
Low-dose Nitric Oxide (NO)
kill bacteria primarily due to its reactive and toxic effects on microbial cells.
- Generation of Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) that are highly toxic to bacterial cells, damaging essential cellular components like DNA, proteins, and lipids.
- Inhibition of enzymes necessary for bacterial cell wall synthesis, susceptible to lysis.
- NO has been shown to be effective in breaking down biofilms— penetrate biofilms and weaken the bacterial community, making individual bacteria more susceptible to immune cells and treatments.
Intrinsically bioactive biomaterials: Cationic materials
Promote cell lysis by exposing functional groups that effectively interact with bacteria cell membranes
Cationic polymers with a net positive charge (backbone or side chain) bind to the negatively charged components of the microbial cell membrane promoting membrane disassembly and leakage or lysis.
- chitosan (in wound dressings, drug formulations, and tissue engineering)
- Antimicrobial peptides (Small cationic peptides, 10-50 amino acids, produced by the innate immune system)
- Synthetic cationic polymers (e.g., Polyethyleneimine (PEI), but has cytotoxicity concerns in human cells)
Intrinsically bioactive biomaterials: Cationic materials advantages
long lifetime and low propensity to induce antibiotic resistance.
control of biofilm formation: Antifouling approaches
Repel microbes, thereby impairing bacterial adhesion and biofilm formation.
(1) Hydrophilic polymers
a) PEG
b) Zwitterionic materials
(2) Superhydrophobic materials
a) “Lotus leaf effect”, unique self-cleaning and bacterial-fouling resistant properties.
b) Can be obtained by combining hydrophobic moieties with proper micro/nanoscale topography.
(3) Materials with nano/microscale surface texture
Bactericidal surfaces: disrupt bacterial cell, causing death (e.g., dragonfly and cicada wings and geiko skin)
Materials with nano/microscale surface texture: nanopillars or nanospikes
Bactericidal Mechanism of nano-
textured surfaces:
Bacteria cell walls stretch and disfigure when they interact with textured surfaces. Stretching occurs in the regions between structures, and if sufficient, cell rupture and death occur.
Quorum sensing
bacterial cell-cell communication within biofilms, primarily known
as “quorum sensing,” is facilitated by the secretion of signaling molecules called autoinducers, which build up concentration gradients within the biofilm environment, allowing bacteria to coordinate their behavior based on the local population density.
control of biofilm formation: Biomaterials affecting biofilm
architecture
Biomaterials expose enzymes or quorum sensing (QS) molecules that modify biofilm structure and enhance biofilm removal by either physical methods or antibiotic treatments.
Biomaterials modified with QS-quenching enzymes
- QS signal molecules include lipids and cyclic or linear peptides.
- Enzymes that degrade these molecules can lead to reduced biofilm thickness, reduced biofilm formation, and interfere with QS pathways
Biofilm matrix-degrading enzymes
- Dispersin-B and DNase I
- These two enzymes can degrade components in the biofilm EPS matrix
Infection Prevention: general principles of sterilization or disinfection of medical devices
In general, reusable medical devices or patient-care equipment that enters normally sterile tissue or the vascular system or through which blood flows should be sterilized before each use.
Sterilization means the use of a physical or chemical procedure to destroy all microbial life, including highly resistant bacterial endospores.
The major sterilizing agents used in hospitals are a) dry heat, b) moist heat by steam autoclaving, c) ethylene oxide gas, and, d) radiation
Disinfection means the use of a chemical procedure that eliminates virtually all recognized pathogenic microorganisms but not necessarily all microbial forms (e.g., bacterial endospores) on inanimate objects.
which of the following best describes the function of an anti-infective coating on a medical device?
it improves the strength and durability of the device
it prevents the adhesion and growth of microoganisms
it promotes biofilm formation on the device surface
it enhances the device’s compatibility with human tissue
It prevents the adhesion and growth of microorganisms
which dressing type prolongs silver release for sustained antimicrobial efficacy?
hydrophilic dressing
hydrophobic dressing
no difference
cannot be determined
hydrophobic dressing
which property of a biomaterial is most likely to reduce bacterial biofilm formation on a medical implant?
micro-scale roughless
high hydrophobicity
nanoscale roughness
high porosity
nanoscale roughness
why are nanotextured surfaces effective in antifouling applications?
they attract bacterial cells with a positive charge, preventing detachment
they make grooves and pits that trap bacteria, making them adhere strongly
they form a hydration layer that prevents bacterial attachment
they have nanoscale features that disrupt bacterial cell walls on contact
they have nanoscale features that disrupt bacterial cell walls on contact
true or false: anti-infective coatings can prevent biofilm formation by directly killing bacteria or blocking attachment to surfaces
true
true or false: hydrophilic coatings are generally less effective in reducing bacterial adhesion compared to hydrophobic coating
false
sterilization
validated process used to render a product free from viable microorganisms
sterile: refers to the absence of microorganisms
sterility assurance level (SAL)
probability of a single microorganism being present in a sterilized product. a statistical measurement of the likelihood that a sterilized item is still non-sterile. SAL=10^-6
most processes are designed to overkill sterilization