Biodegradable polymers for biomaterials Flashcards
What is meant by biodegradable?
solid polymer reduced to soluble fragments that are either excretable or metabolized under physiological conditions (saline environment, pH 7.4, 37°C)
When, generally, are biodegradable implants desirable?
one-time surgeries where a device does not need to be retrieved after living out its useful lifetime
When are biodegradable/bioresorbable polymers needed in implants?
1) Temporary needs Fill and support bone defect until natural bone grows back: TE Provide drug delivery until condition is corrected
2) Avoid chronic inflammation and long-term implications Loosening in artificial hip
3) Limited alternatives in eliminable materials devices (PEG, dextran)
What are the different types of biodegradable polymers?
- polyglycolic acid
- polylactic acid
- polycaprolactone
- polyhydroxybutyrate-co-valerate
Why are there only a few biodegradable polymers?
need to be FDA approved, thermoplasts
Why is Polyglycerol sebacate not a biodegradable polymer used in medical applications?
Not FDA approved but made from 2 natural materials
Thermoset
Tg= -35°C, elastomer
Why are polymers prone to hydrolysis?
Formed via condensation route
Addition polymers may contain side groups that are capable of being hydrolysed
- Polyesters based on [-R-COO-]n are often susceptible to hydrolysis
Acid and base-catalysed hydrolysis (saponification)
What is the reaction of Acid and base-catalysed hydrolysis (saponification)?
ROOH + R’OH ROOR’ +H2O
What are the degradation mechanisms for biodegradable biomaterials?
cleaving of the backbone
Which factors affect degradation rate?
Molecular structure effects on hydrolytic breakdown
Water needs to access bonds so structure and hydrophobicity has strong effect on hydrolysis rate
Factors influencing hydrolysis rate: • Bond stability • Hydrophobicity PHBV ~ PCL (years) < PLA (months) < PGA (weeks) • Dynamical steric effects (Tg) • Crystallinity
How does relative bond stability affect degradation rate for biodegradable polymers?
- Bond half lifetime at physiological pH/T
- Intrinsic stability of polyamide
- Polypeptides are degradable due to enzyme action
- Nylon is not/less biodegradable
How does crystallinity affect the degradation rate of degradable polymers?
- Amorphous polymers degrade faster than crystalline polymers
- Semi-crystalline polymer: Amorphous regions decompose earlier
- Crystallinity increases through degradation
What are examples of environmental degradation?
- hydrolysis
- photolysis(UV)
- heat
- friction
What are examples of biodegradation?
Enzymes
- lipase (breaks down fat via hydrolysis)
- Esterase (hydrolyses esters)
- Protease (breaks down proteins, residue specific)
- Oxidase/reductase
Or whole cells (i.e. combinations of reactions) Bacteria - mammalian cells
How does biodegradation occur as a result of cells?
Inflammation
- Macrophages and neutrophils around the implant undergo a oxidative burst producing superoxides. Superoxide (O2-) can be converted to peroxide by superoxide dismutase (SOD)
- Peroxide and superoxide are converted into hydroxyl radical (HO•) in presence of iron or transition metal ions
- Hydroxyl radicals are highly toxic and aid the macrophages to kill the invading micro-organisms
- Biopolymer degradation rates are also strongly affected by HO
How is biodegradation affected with a hydroxyl radical?
Both PLA and PCL degrade markedly faster in presence of the HO• radical
What are hydrogels?
Insoluble network of polymer chains that swell in aqueous solutions
Gels can be qualified by crosslinker:
Covalent: covalent junctions
Physical: non-covalent junctions
Why are Hydrogels used as scaffolds for cell culture and tissue engineering applications?
Extracellullar matrix is hydrogel
Soft tissues: Extracellullar matrix is a hydrogel of elastin and collagen fibres together with cell binding protein (e.g. fibronectin) that envelop cells. Cells interact with fibres via integrin binding Can we mimic this 3D environment in hydrogels
What are the options for 3D scaffolds?
- Microporous scaffolds: pore size, might be described as 2D curved surfaces
- Nanofibrous scaffolds: can mimic the nanofibrillar architecture formed by fibrillar ECM proteins
- Hydrogels: can capture numerous characteristics of the architecture and mechanics of the native cellular environment
What is the difference between promoting and permissive hydrogels?
PROMOTING
- natural gels
- factors included in gel
- promote cell function
- complex and ill defined
PERMISSIVE
- synthtic gels
- no integrin binding with cells
- reproducible facile manufacture
- minimalist approach
What is the future in building ECM mimic?
Creating tailored permissive hydrogel that includes both features to enhance cell ingrowth and user control of growth
How are materials made non-adhesive?
1st approach: Make surface hydrophobic
surface energy polymers
For non-fouling: Bacteria, Fungi, Proteins, cells
What is the concept of making a material non-adhesive?
Hydrophobic surface - Low surface energy - high contact angle Hydrophilic surface- Low contact angle WATER: HIGH SURFACE ENERGY
Which hydrophobic medical polymers?
- Polysiloxanes
- Fluorinated polymers
