8/11/2021

DEGRADATION OF MATERIALS IN THE

BIOLOGICAL ENVIRONMENT. Part I

PhD. Silvia Milena Becerra Bayona PhD. Víctor Alfonso Solarte David

THE BODY FIGHTS BACK

• Biological environment: seemingly a mild

aqueous salt solution

• But…. It is surprisingly aggressive

• It can lead to rapid or gradual breakdown

of many materials

Why is that?

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THE BODY FIGHTS BACK

Some of the problems….

• Cyclic or periodic stress

• Abrasion and flexure
• Aqueous, ionic environment

Electrochemically Plasticizing to
active to metals polymers
(softening)

THE BODY FIGHTS BACK

Also….

• Specific biological mechanisms

• Proteins adsorb to the material
• Enhance the corrosion rate of metals

Macrophages Secretion of
secrete powerful enzymes that
oxidizing agents dissolve the
material

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THE BODY FIGHTS BACK

Also….
Presence of cracks
• Specific biological mechanisms
• Proteins adsorb to the material
• Enhance the corrosion rate of metals Swelling and water uptake

pH alteration
Macrophages Secretion of
secrete powerful enzymes that Hydrolysis of hydrophobic
oxidizing agents dissolve the polymers
material

THE BODY FIGHTS BACK

Also….

• Specific biological mechanisms A specific time after implantation

• Proteins adsorb to the material
• Enhance the corrosion rate of metals

An unexpected long-term
consequence of the severity of the
Macrophages Secretion of
biological environment
secrete powerful enzymes that
oxidizing agents dissolve the
material

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CHEMICAL AND BIOCHEMICAL DEGRADATION OF

POLYMERS INTENDED TO BE BIOSTABLE

What is biodegradation?

CHEMICAL AND BIOCHEMICAL DEGRADATION OF

POLYMERS INTENDED TO BE BIOSTABLE

Biodegradation is the
chemical breakdown of
materials by the action of
living organisms that leads
to changes in physical
properties

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Polymer degradation processes: pre-implant degradation

Polymer Pellets Compone Device

nt

Synthesis Packaging Injection-molding Fabrication storage (pre-sterilization)

Extrusion Storage Post-mold-finishing Inspecting
Pelletizing Transfer Cleaning Packaging
Drying Inspecting Storage
Packaging storage Sterilization
Storage
shipment
Mechanisms of physical and chemical deterioration

Polymer degradation processes: post-implant degradation

water, ions, water, ions,

proteins,
proteins, and lipids

and lipids

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Polymer degradation processes: post-implant degradation

Hydrolytic Biodegradation

Hydrolysis is the scission of

susceptible molecular
functional groups by
reaction with water

But…..

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Hydrolytic Biodegradation

Hydrolysis is the scission of

susceptible molecular
functional groups by
reaction with water

It may be catalyzed by acids, bases, salts or enzymes

Hydrolytic Biodegradation

The rate of initiation is directly

Polymer’s
proportional to the rate of chain susceptibility
scission

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Hydrolytic Biodegradation

Functional groups
Hydrolyzable
contain C bonded
polymers
to O, N, S

Esters Urethanes

Amides Carbonates

Anhydrides

Host-induced hydrolytic processes

Normal in vitro environment Lead to hydrolysis in vivo

Highly controlled Water permeation (pH 7,0)
Isothermal (37 °C) Ion-catalyzed hydrolysis
Neutral (pH 7,4) Localized pH changes (infection)
Aseptic Presence of enzyme
Photo-protected Cell-derived enzymes

Cell adhesion, cell activation, chemical reaction, and particulate transport

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Some examples…

• Large-diameter vascular prostheses

• Strong, flexible polymer, with high

crystallinity

• Considered biostable…but…
Poly(ethylene terephthalate): PET
• Long-term degeneration of devices in vivo

Some examples…

• Use: plastic and orthopedic reconstructive surgery

• Initial degradation: ester soft segments
• In contrast: poly(ether urethanes) are very resistant to hydrolysis (more susceptible to
oxidation)

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Oxidative biodegradation

Oxidative biodegradation
involves the disintegration
of polymers by action of
oxygen to allow abstraction
of an atom or ion

Oxidative biodegradation

• Products: carbonyl, hydroxyl, and

chain scission products

• It consists of an initiation,
propagation and termination

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Oxidative biodegradation

Oxidative oxidizable functional groups

Oxidative biodegradation: direct oxidation by host

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Oxidative biodegradation: direct oxidation by host

Oxidative biodegradation: direct oxidation by host

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Oxidative biodegradation: stress cracking

Oxidative biodegradation: environment-mediated

Metal ion-induced oxidation

• Initiation: the enclosed inner surfaces near

corroded metallic components

• Brittle fracture

• Degradation products are found deeper

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BIODEGRADATION OF BIODEGRADABLE POLYMERIC

BIOMATERIALS

Overview of biodegradable polymers

• Applications: dated back to 1960

(suture materials, unstable)
• Natural and synthetic origin
• Biodegradable

What does it mean?

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Overview of biodegradable polymers

• Biodegradable

 almost all polymers will degrade

eventually
 only those with therapeutically-
relevant degradation rates are
considered biodegradable

Overview of biodegradable polymers

What is the advantage of

using synthetic polymers?

synthetic polymers can be synthesized in a

highly controllable and reproducible manner

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Overview of biodegradable polymers

Benefits

Synthesis

Highly Controlled User-designed

and reproducible degradability

Defined
properties

Overview of biodegradable polymers

Benefits

Applications

Lack of Tissue
immunogenicity engineering

Drug delivery

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Overview of biodegradable polymers

Types of Degradation Effect of
biodegradable modes and biodegradation
chemical bonds mechanisms of on material
biodegradation properties

Characteristics of biodegradable polymers

What does it mean degradation?

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Characteristics of biodegradable polymers

What does it mean degradation?

Characteristics of biodegradable polymers

Mechanisms of
Polymer
degradation in vivo
Hydrolytic

Thermal Photodegradation Enzymatic

Mechanical

Which ones will imply biodegradation?

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Characteristics of biodegradable polymers

Biodegradation is commonly
used when degradation
involves biological
processes, such as body
fluids, cellular activities, and
enzymatic reactions

Characteristics of biodegradable polymers

What does affect the rate of polymer degradation?

• The biological environment

 Faster: inflammatory environment.

Due to: excessive biological and
biochemical activity
 pH
 Temperature
 Enzyme concentrations
 Cell infiltration/recruitment

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Characteristics of biodegradable polymers

What does affect the rate of polymer degradation?

• The biological environment • Polymer properties

 Faster: inflammatory environment.  Chemistry

Due to: excessive biological and  Physical appearance
biochemical activity  Morphology
 pH  Hydrophobic polymers: limit water
 Temperature accessibility, decreased hydrolytic
 Enzyme concentrations degradation rate
 Cell infiltration/recruitment

Characteristics of biodegradable polymers

What does affect the rate of polymer degradation?

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Characteristics of biodegradable polymers

What does affect the rate of polymer degradation?

• Polymer properties • Degradation rate and…

 Chemistry  Amorphous vs semicrystalline?

 Physical appearance
 Morphology  High Tg vs low Tg?
 Hydrophobic polymers: limit water
accessibility, decreased hydrolytic
degradation rate

Characteristics of biodegradable polymers

What does affect the rate of polymer degradation?

• Biodegradation is a dynamic process, why?

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Characteristics of biodegradable polymers

What does affect the rate of polymer degradation?

• Biodegradation is a dynamic process, why?

 Polymer properties change with degradation. For example:

 In the case of semicrystalline polymers:

• Amorphous parts degrade faster

• Polymer crystallinity increases with time
• The degradation rate decreases with time
• Generation of some monomers, for example, acidic monomers, can
increase the pH, and auto-accelerated degradation of the polymer

Hydrolytically biodegradable polymer bonds

• The type of chemical bond in the backbone of a biodegradable polymer plays a major role
in dictating the rate of bond cleavage

 Faster: anhydride and ortho-ester bonds

 Followed by ester and thioether bonds

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Hydrolytically biodegradable polymer bonds

• The type of chemical bond in the backbone of a biodegradable polymer plays a major role
in dictating the rate of bond cleavage

 Faster: anhydride and ortho-ester bonds

 Followed by ester and thioether bonds

• However….it is affected by:

 The presence of hydrophobic functional groups

 The altered local pH
 Molecular weight of the polymer
 Composition of the copolymer

Hydrolytically biodegradable polymer bonds

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Hydrolytically biodegradable polymer bonds

Polyester hydrolysis

Hydrolytically biodegradable polymer bonds

Polyanhydrides Poly(ortho esters)

Hydrophobicity limits water They are more hydrophobic
penetration
Fast hydrolysis Slower degradation rates
Surface erosion Surface erosion
Products are metabolized by the
Products: acids and alcohols
body
Applications: short-term drug Applications: controlled release
release devices

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Hydrolytically biodegradable polymer bonds

Poly(alpha-hydroxy esters)

Hydrolytically biodegradable polymer bonds

Poly(alpha-hydroxy esters)

• First synthetic polymers with clinical applications: PGA,

biodegradable suture material

• Hydrolysis: at the ester bonds

• Governed by: accessibility of water

• PLA degrades more slowly than PGA. Why?

• Products: lactic acid and glycolic acid. What would be

the implications?

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Modes of biodegradation

Mainly occurs in hydrophobic polymers

Mainly occurs in hydrolytic polymers

Why?

Modes of biodegradation: surface erosion

• Mainly occurs in hydrophobic

polymers

• The rate of bond cleavage is faster

than the rate of water diffusion into the
polymer

• Degradation is limited to surface

• Applications: drug delivery, release is

Polyanhydrides, poly(ortho esters) independent of diffusion

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Modes of biodegradation: bulk erosion

• Bonds are cleaved throughout the

polymeric device

• Change in molecular weight

• Increasing water content, libration of

soluble monomers and chain fragments

• Dramatic changes in mechanical

Poly(alpha-hydroxy esters), PEG, PVA, PAA,
pHEMA, pNIPAM
properties

Release rate: governed by diffusion and mass loss

of the polymer

Enzymatic degradation

Governed by enzymatic reactions

Enzyme
concentration Kinetics of the enzymatic
Location
reaction

Surface erosion Bulk erosion

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Enzymatic degradation

For hydrophilic polymers, do you

expect to have surface or bulk
erosion in presence of enzymes?

Enzymatic degradation

For hydrophilic polymers, do you

expect to have surface or bulk
erosion in presence of enzymes?

It depends…..

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Enzymatic degradation

For hydrophilic polymers, do you expect to have surface or bulk erosion in presence of
enzymes?

• Rate of enzymatic polymer bond cleavage (1) vs. rate of enzyme diffusion (2)

• If (1) is higher than (2): surface erosion

• If (1) is lower than (2): bulk erosion. Example: polymers with enzymatic cleavable
units in their backbone

It depends…..

Enzymatic degradation

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Enzymatic degradation

Influence of biodegradation on properties of

biodegradable polymers and their application

• Development in numerous drug delivery and controlled release formulations

• Surface erosion
• Bulk-degradation mediated release
• Pendent chain cleavage mediated release

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Drug delivery: influence of biodegradation in diffusion

Typical release Corresponding
Protein or small
profile rate
molecule drug
Release rate

Amount of drug release

t t

Typical release Corresponding

Protein or small
profile rate
molecule drug
Amount of drug release Release rate

Toxic dose

dc(t)/dt

C(n)/t
t t t

Drug delivery: influence of biodegradation in diffusion

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Drug delivery: influence of biodegradation in diffusion

Any other important applications???

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Tissue Engineering

Tissue Engineering
Heparin bound Local release of heparin
Heparin growth factor bound growth factors
Degradation of
hydrogel

MMPs released from

infiltrating cells in vivo
Cell migration and
organization of vasculature

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