Bioabsorbable Polymers Quiz

Polymers as Biomaterials

• Polymers are used as biomaterials for their variety in composition, properties, and available forms (e.g., solid, elastic, hydrogel)
• They are easy to manufacture into complex shapes (sheets, fibers, powders, films)
• Biodegradable polymers have reasonable costs, and are used in load-bearing applications
• Biostable polymers have a more complex structure, with mechanical properties and thermal resistance, and have higher prices.

Biodegradation Mechanisms

• Hydrolytic degradation is a chemical reaction where water breaks up bonds in a material
• Chain scission is when water molecules separate certain bonds in the material
• Enzymatic degradation is when enzymes (proteins in tissues) catalyze biochemical reactions like hydrolysis or oxidation
• Both hydrolyitic and enzymatic degradation produce low molecular weight products that are soluble and metabolized by the body

Classification of Polymers

• Biostable polymers
• Bioabsorbable polymers
• Natural polymers, including modified natural polymers
• Synthetic polymers

Classification of Biostable Polymers

• Mass production of biostable polymers lead to technical/engineering specialty polymers, increasing in use and cost as the structure becomes more complex

Why Polymers in Medicine?

• Variety of compositions and properties
• Easy to fabricate complex forms (sheets, fibers)
• Reasonable costs
• Biodegradable
• Lower strength and moduli than metals and ceramics (usually not suited for load-bearing applications)

Bioabsorbable Implants

• Implants avoiding removal surgery
• No long-term implant complications, palpability, or temperature sensitivity
• No risk for children’s growth disturbance or stress shielding
• Avoiding trauma from traditional implant removal
• Patient satisfaction due to less pain

Definitions

• Biodegradation: breakdown of a material by a biological system
• Bioabsorbable/bioresorbable: capable of degradation/dissolving and metabolized within an organism

A Couple of Minutes to Discuss

• Many polymers are considered plastics that can degrade in the body without causing reactions, but some are not truly metabolized
• Microplastics in the body may be relevant only for biostable polymers dissolved into microparticles

How Long Is The Degradation Time?

• The length depends on the characteristics of the material, including
  • Material properties (hydrophobic vs hydrophilic, polymer structure/morphology)
  • Molecular weight
  • Manufacturing process (parameters, sterilization)
  • Implantation site (inside vs. outside bone, tissue layer thickness, and vascularity/blood circulation)
• Individual differences in metabolism and/or local vascularity/blood circulation affect degradation

How the Degradation Behavior is Tested?

• A combination of methods is required
• Measure and analyze different properties along the degradation process, including mass loss, molecular weight, crystallinity, etc.

Enzymatic Degradation

• Enzymes (proteins in tissues) have a particular affinity for certain chemical groups present in polymers
• They catalyze biochemical reactions like hydrolysis and oxidation in the body
• (May occur at a later stage in degradation of materials that degrade via hydrolysis, when the initial stages have already already happened)

Hydrolytic and Enzymatic Degradation

• Both mechanisms produce low molecular weight, water-soluble products that the body metabolizes
• The mechanisms can exist in combination

Common Synthetic, Bioabsorbable Polymers

• Synthetic polymers include hydroxy acids, vinylic polymers, polyesters, and their copolymers
• Various types of polymers are used:
  • Poly(glycolic acid) (PGA) (homopolymer)
  • Poly(lactic acid) (PLA) (homopolymer)
  • Poly(ε-caprolactone) (PCL) (homopolymer)
  • Poly(butylene succinate) (PBS) (copolymer)
  • Poly(lactic-co-glycolic acid) (PLGA) (copolymer)
  • Others copolymers

Bioabsorbable Synthetic Polymers

• Polyesters including PGA, PLA, PCL, PBS, PLGA, and others

Polyglycolide (PGA)

• Highly crystalline
• High melting point
• Low solubility in organic solvents
• Used early development of totally synthetic, bioabsorbable sutures (Dexon)

Polyglycolide(PGA) for Degradation

• Degradation involves hydrolysis and enzymatic degradation
• The degradation products (glycolic acid) are eliminated through the metabolic pathway as CO2 and H2O
• Bulk PGA degrades and is absorbed relatively quickly compared to PLA
• Copolymerization with more hydrophobic lactide can provide a wider range of polymer properties

Biodegradable Synthetic Polymers - Polylactides

• Polymers obtained from different isomers (PLLA, PDLA, PDLLA) and copolymers, which have different properties
• Different degradation rates, physical, and chemical characteristics (can be adjusted) can be processed in different ways
• Polyesters have a slow degradation rate
• Significantly hydrophobic

Polylactide (PLA)

• PLA degrades by bulk hydrolysis of ester bonds to lactic acid
• Lactic acid is a byproduct of anaerobic metabolism in the human body
• The complete degradation takes 3-5 years for some forms (longer than PGA)

Poly-ɛ-caprolactone (PCL)

• Degrades relatively slowly compared to PLA
• Accompanied by enzymatic degradation at a later stage
• Slower degradation and mass absorption
• Copolymerized with lactide, glycolide, etc.
• Mixed with other polymers well

Copolymers

• Homopolymer properties may not be sufficient for medical applications
• Copolymerization can modify properties such as mechanical properties, degradation, and crystallinity

Copolymers for Medical Uses

• Polymer response to stress/strain depends on variables like strain rate, temperature, and time
• This viscoelastic behavior can be modified via copolymers (blending of polymers or copolymerization of different monomers)
• Typical copolymer materials for lactides are glycolide and trimethylene carbonate

What's Wrong with the Early Generation Biodegradables?

• PGA (semi-crystalline, hydrophilic, fast degradation, rapid strength loss) lead to higher risk of inflammation in adult patients
• PLLA (high crystallinity, hydrophobic, very slow, unpredictable degradation) lead to late inflammatory response
• Crystalline residue also results in a longer degradation period

Poly(lactide-co-glycolide) (PLGA)

• Is amongst the most studied bioabsorbable polymers
• Well-known properties
• Biocompatible
• Simple processing
• Degrades to lactic acid and glycolic acid
• Possible modification

Poly(lactide-co-caprolactone) (PLCL)

• Flexible
• Good drug release properties
• Tailorable properties dependent on ratio of monomers
• Degrades faster than their respective homopolymers

Materials Selection

• Selection of materials based on factors like strength, flexibility, and degradation characteristics for various application needs, like implants, screws, plates, and nails

Summary of Synthetic, Bioabsorbable Polymers

• Bioabsorbable polymers are used temporary function/support
• Hydrolytic degradation with synthetic biopolymers (BPs)
• Processing similar to stable polymers (mostly melt processing)
• Variety in shapes and geometries (often without solvents)

(Modified) Natural Bioabsorbable Polymers

• Derived from nature (animals and plants)
• Can be modified
• Offer good biocompatibility and degradability, but have disadvantages
• Poor mechanical properties
• Batch-to-batch variations
• Difficulty processing

Future of Bioabsorbable Polymers

• Metal-based implants may be replaced by biocompatible, sustainable polymers, and/or tissues

General Announcements

• Visit schedule, lectures, and hands-on sessions
• Exam schedule and details
• Enrolment information

Hydrogels

• Hydrophilic polymeric network that swells in water without dissolving
• Soft and rubbery, containing large amounts of water

Hydrogel Applications

• Carriers for drug delivery, wound dressings, contact lenses, and tissue engineering scaffolds

Injectable Hydrogels

• Formulation, methods of chemical/physical crosslinking, and applications relating to polymers

Summary of (Modified) Natural Polymers

• Polymers are derived from nature (animals and plants)
• Natural polymers often have good biocompatibility and degradability
• The main disadvantages are poor mechanical properties and batch-to-batch variation, as well as difficulty in processing

Why growing interest in Natural polymers?

• Growth of tissue engineering
• Continuous search for better implant material
• Increased biocompatibility
• Increased cell adhesion, migration, and proliferation
• Enzymatic degradation
• Everyday uses: starch-based bags, paper coating

Natural Polymers (main proteins of the ECM)

• Collagen: Main protein in the ECM
• Gelatin: Low MW derivative of collagen
• Fibrin: Insoluble network of polymerized blood proteins
• Elastin: Highly elastic protein in connective tissue
• Hyaluronic acid: Important polysaccharide of the ECM
• Chitosan: Polysaccharide derived from chitin (deacetylation)
• Alginate: Polysaccharide obtained from cell walls
• Silk fibroin: Fibrous protein from silkworms

How To Obtain Natural Polymers?

• Natural polymers are not always ready-for-use: extraction, purification, and often modification are needed
• Series of treatments (chemical and heat), and recombination of proteins, may be needed to make the polymer suitable for use.