Biomaterials 1 summary
Lecture 1
Biological material properties
- Softness: soft tissues, organs
- Hardness: hard tissues, bones
- Flexibility and stiffness: cartilage, skin. Cartilage is not as stiff as bone but stiffer than soft
tissues. Skin is highly flexible.
- Self-assembled: cells
- Nano-micro-macro: molecule, cell, tissue
- Water-based. Many biomaterials function because of water. E.g. aggregation is based on
hydrophobic interactions and only work in polar environment. Also, degradable polymers
only hydrolyze when water is present.
Water is both an acid and a base and therefore also a nucleophile and an electrophile. The ability for
coordination makes water present everywhere. Coordination to:
- Positively charged surfaces. The partial negative charge interacts with the positive surface.
- Negatively charged surfaces. The partial positive charge on the H-atoms interact with the
negative surface.
- Neutral polar surfaces
- Non-charged apolar/hydrophobic surfaces
This is because of the way the electrons are distributed. There are partial positive and negative
charges.
Synthetic material properties
- Polymers: can be soft, hard, flexible, water-based, self-assembled, hydrophilic/hydrophobic,
responsive dynamic.
- Metals/metaloxides: strong, hard.
- Small organic molecules: self-assembly, electronic properties.
Nano → micro → macro
Atoms → supramolecular structures → tissue & higher organisms
There are a lot of surrounding structures and conditions that the biomaterial is in, like water, salts,
proteins, temperature, mechanical stress and sterilization conditions. The inside of the biomaterial
does not have these conditions, like on the surface.
Besides that, we also need to consider the operation conditions.
- Dry vs wet
- Temperature
- Invo vs. in vitro
- Mechanical load and structural integrity
In vivo (inside) vs ex vivo (on skin e.g.) operations. For example in vivo, water is present, a body
temperature of 37 degrees, proteins, cells, macrophages etc. while ex vivo has no/little water,
varying temperatures, high oxygen, radiation etc. Due to the presence of water, a material can be
dissolved and the initial function will be lost. The material can also get oxidized (rust). The material
properties will change.
The body has a wide range of pH, therefore not all materials perform equally well at different
positions. It also has a wide range of enzymes able to perform many reactions (hydrolysis, oxidation).
Temperature → increase with 10 degrees, the reaction goes twice as fast.
Applied stress → a material can go with a certain amount of stress. There is a change in material
properties due to stress. If you have a fracture in your biomaterial → more surface and more contact
with water. Water, pollution, enzymes etc. can target the material.
,In vivo = in lab. What factors to consider:
1. Influence of the body on the material.
a. Dissolution
b. Degradation
c. Pollution
i. Can be caused by: water, oxygen, enzymes and other proteins and cells.
2. Influence of the material on the body.
Perfect prediction is very difficult. Therefore, we need to identify all parameters and behaviors of
both materials and biological response as accurately as possible.
Lecture 2
Review paper → non-research paper.
Writing order: References; main text; conclusion (&discussion); introduction; abstract; title.
Abstract = short teaser providing question, approach and conclusion.
Conclusion:
- Provides statement on usefulness
- Comparison made with other systems available
- Provides insights in which factors are important for the future.
Introduction:
- Funneling. Goes into more detail towards the end.
- Use per claim a citation. Even if it is the same source as before. It is okay to use one source
multiple times. This also accounts for the rest of the text.
Abstract:
- Needs to contain the scope, motivation and the main conclusion.
- Short and to the point.
Lecture 3: condensation polymers
Polymer = made out of monomers. When you attach multiple monomers to each other, you get a
linear homopolymer. There are two (growth) mechanisms in which a monomer becomes a polymer:
- Monomer → dimer → trimer → tetramer → etc. So in each step a monomer is added to the
chain = chain growth polymerization. There is one addition at a time.
o No small molecule splitting off.
o Initiator needed.
o Only initiated chains grow and growth only with monomers. The growth is short
between initiation and termination.
o There is often a termination reaction.
o The number of polymer chains remain the same, but length increases.
- Dimer → tetramer → hexamer etc. So in each step a dimer is added to the chain = step
growth polymerization.
o During the process a small molecule, like water, alcohol or other small molecules,
splits off = condensation.
o No initiator needed. The reactivity is intrinsic to the monomer.
o All chains react with each other. There is continuous reaction.
o Usually no termination reaction.
o Many small polymers grow to fewer larger ones.
, Step growth polymerization: condensation polymers.
The condensation polymers grow with the step growth mechanism.
If you make a polymer out of two different monomers, you get a linear ‘random copolymer’. There is
no particular order in which the monomers are ordered in the polymer. By better tuning the
polymerization, it changes the polymer response and hence the polymeric biomaterial. Besides a
random copolymer, in which two monomers follow in any order, you also have an alternating
copolymer = when the two monomers are arranged in alternating fashion, so A – B – A – B etc. There
is also a block copolymer. All of one type monomers are grouped together and all of the other are
grouped together. A block copolymer can be thought of as two homopolymers joined together at the
ends, so AAAAAA-BBBBBB.
Polymer properties are based on topology, composition, functionality and molecular weight
distribution. The topology can be linear, but also like a star, comb, network or hyperbranched. The
composition can be (like discussed above) a homopolymer, random copolymer, block copolymer, but
also a graft copolymer or tapered/gradient copolymer. The molecular weight distribution is based on
linkages (meso, cis etc.; how the side groups are arranged in a polymer).
Property variations in polymers
- Molecular weight
- Molecular weight distribution
Variations affect:
- Viscosity
- Melting temperature (Tm)
- Glass transition temperature (Tg)
- Solubility
- Processing
Copolymers can be used for/as degradable biomaterials.
- Polylactic acid (PLA). The backbone [~OCH(CH3)CO~].
- Polyglycolic acid (PGA). The backbone [~OCH2CO~].
- Polylactic-co-glycolid acid (PLGA). The backbone is a combination of PLA and PGA. It is a
copolymer. The only difference between PLA and PGA is the ‘extra’ methyl group in PLA in
the monomer.
Why is PLA degradable?
The PLA structure contains an ester (see image on the right).
Carboxylic acid + alcohol = ester.
When you have a molecule with on two sides a carboxylic acid group and a
molecule with on both sides hydroxy groups/alcohol, you can synthesize a
polymer with an ester. Upon the formation, one molecule of water is
formed for a connection made.
An ester bond is weak. This weak bond can be disconnected/cleaved by water. When the bond is
cleaved, it is cleaved between the carbonyl and the oxygen bond (so between the C=O and the O).
you will get an carboxylic acid and an alcohol again.
The requirement for degradability is that the polymer itself is insoluble and the monomer soluble.
When you look at the monomer of PLA, lactic acid, the OH group is a nucleophile (partial negative
charge on the oxygen) and the carbon from the C=O is an electrophile (partial positive charge). The
OH-group is the leaving group.
Nucleophile: has enough electrons available to ‘give’ them to an electron density ‘deficient’ atom. it
donates an electron pair to form a chemical bond in relation to a reaction. All molecules or ions with
a free pair of electrons or at least one pi bond can act as nucleophiles.
Electrophile: would like to take-up extra electrons due to electron density deficiency.
Lecture 1
Biological material properties
- Softness: soft tissues, organs
- Hardness: hard tissues, bones
- Flexibility and stiffness: cartilage, skin. Cartilage is not as stiff as bone but stiffer than soft
tissues. Skin is highly flexible.
- Self-assembled: cells
- Nano-micro-macro: molecule, cell, tissue
- Water-based. Many biomaterials function because of water. E.g. aggregation is based on
hydrophobic interactions and only work in polar environment. Also, degradable polymers
only hydrolyze when water is present.
Water is both an acid and a base and therefore also a nucleophile and an electrophile. The ability for
coordination makes water present everywhere. Coordination to:
- Positively charged surfaces. The partial negative charge interacts with the positive surface.
- Negatively charged surfaces. The partial positive charge on the H-atoms interact with the
negative surface.
- Neutral polar surfaces
- Non-charged apolar/hydrophobic surfaces
This is because of the way the electrons are distributed. There are partial positive and negative
charges.
Synthetic material properties
- Polymers: can be soft, hard, flexible, water-based, self-assembled, hydrophilic/hydrophobic,
responsive dynamic.
- Metals/metaloxides: strong, hard.
- Small organic molecules: self-assembly, electronic properties.
Nano → micro → macro
Atoms → supramolecular structures → tissue & higher organisms
There are a lot of surrounding structures and conditions that the biomaterial is in, like water, salts,
proteins, temperature, mechanical stress and sterilization conditions. The inside of the biomaterial
does not have these conditions, like on the surface.
Besides that, we also need to consider the operation conditions.
- Dry vs wet
- Temperature
- Invo vs. in vitro
- Mechanical load and structural integrity
In vivo (inside) vs ex vivo (on skin e.g.) operations. For example in vivo, water is present, a body
temperature of 37 degrees, proteins, cells, macrophages etc. while ex vivo has no/little water,
varying temperatures, high oxygen, radiation etc. Due to the presence of water, a material can be
dissolved and the initial function will be lost. The material can also get oxidized (rust). The material
properties will change.
The body has a wide range of pH, therefore not all materials perform equally well at different
positions. It also has a wide range of enzymes able to perform many reactions (hydrolysis, oxidation).
Temperature → increase with 10 degrees, the reaction goes twice as fast.
Applied stress → a material can go with a certain amount of stress. There is a change in material
properties due to stress. If you have a fracture in your biomaterial → more surface and more contact
with water. Water, pollution, enzymes etc. can target the material.
,In vivo = in lab. What factors to consider:
1. Influence of the body on the material.
a. Dissolution
b. Degradation
c. Pollution
i. Can be caused by: water, oxygen, enzymes and other proteins and cells.
2. Influence of the material on the body.
Perfect prediction is very difficult. Therefore, we need to identify all parameters and behaviors of
both materials and biological response as accurately as possible.
Lecture 2
Review paper → non-research paper.
Writing order: References; main text; conclusion (&discussion); introduction; abstract; title.
Abstract = short teaser providing question, approach and conclusion.
Conclusion:
- Provides statement on usefulness
- Comparison made with other systems available
- Provides insights in which factors are important for the future.
Introduction:
- Funneling. Goes into more detail towards the end.
- Use per claim a citation. Even if it is the same source as before. It is okay to use one source
multiple times. This also accounts for the rest of the text.
Abstract:
- Needs to contain the scope, motivation and the main conclusion.
- Short and to the point.
Lecture 3: condensation polymers
Polymer = made out of monomers. When you attach multiple monomers to each other, you get a
linear homopolymer. There are two (growth) mechanisms in which a monomer becomes a polymer:
- Monomer → dimer → trimer → tetramer → etc. So in each step a monomer is added to the
chain = chain growth polymerization. There is one addition at a time.
o No small molecule splitting off.
o Initiator needed.
o Only initiated chains grow and growth only with monomers. The growth is short
between initiation and termination.
o There is often a termination reaction.
o The number of polymer chains remain the same, but length increases.
- Dimer → tetramer → hexamer etc. So in each step a dimer is added to the chain = step
growth polymerization.
o During the process a small molecule, like water, alcohol or other small molecules,
splits off = condensation.
o No initiator needed. The reactivity is intrinsic to the monomer.
o All chains react with each other. There is continuous reaction.
o Usually no termination reaction.
o Many small polymers grow to fewer larger ones.
, Step growth polymerization: condensation polymers.
The condensation polymers grow with the step growth mechanism.
If you make a polymer out of two different monomers, you get a linear ‘random copolymer’. There is
no particular order in which the monomers are ordered in the polymer. By better tuning the
polymerization, it changes the polymer response and hence the polymeric biomaterial. Besides a
random copolymer, in which two monomers follow in any order, you also have an alternating
copolymer = when the two monomers are arranged in alternating fashion, so A – B – A – B etc. There
is also a block copolymer. All of one type monomers are grouped together and all of the other are
grouped together. A block copolymer can be thought of as two homopolymers joined together at the
ends, so AAAAAA-BBBBBB.
Polymer properties are based on topology, composition, functionality and molecular weight
distribution. The topology can be linear, but also like a star, comb, network or hyperbranched. The
composition can be (like discussed above) a homopolymer, random copolymer, block copolymer, but
also a graft copolymer or tapered/gradient copolymer. The molecular weight distribution is based on
linkages (meso, cis etc.; how the side groups are arranged in a polymer).
Property variations in polymers
- Molecular weight
- Molecular weight distribution
Variations affect:
- Viscosity
- Melting temperature (Tm)
- Glass transition temperature (Tg)
- Solubility
- Processing
Copolymers can be used for/as degradable biomaterials.
- Polylactic acid (PLA). The backbone [~OCH(CH3)CO~].
- Polyglycolic acid (PGA). The backbone [~OCH2CO~].
- Polylactic-co-glycolid acid (PLGA). The backbone is a combination of PLA and PGA. It is a
copolymer. The only difference between PLA and PGA is the ‘extra’ methyl group in PLA in
the monomer.
Why is PLA degradable?
The PLA structure contains an ester (see image on the right).
Carboxylic acid + alcohol = ester.
When you have a molecule with on two sides a carboxylic acid group and a
molecule with on both sides hydroxy groups/alcohol, you can synthesize a
polymer with an ester. Upon the formation, one molecule of water is
formed for a connection made.
An ester bond is weak. This weak bond can be disconnected/cleaved by water. When the bond is
cleaved, it is cleaved between the carbonyl and the oxygen bond (so between the C=O and the O).
you will get an carboxylic acid and an alcohol again.
The requirement for degradability is that the polymer itself is insoluble and the monomer soluble.
When you look at the monomer of PLA, lactic acid, the OH group is a nucleophile (partial negative
charge on the oxygen) and the carbon from the C=O is an electrophile (partial positive charge). The
OH-group is the leaving group.
Nucleophile: has enough electrons available to ‘give’ them to an electron density ‘deficient’ atom. it
donates an electron pair to form a chemical bond in relation to a reaction. All molecules or ions with
a free pair of electrons or at least one pi bond can act as nucleophiles.
Electrophile: would like to take-up extra electrons due to electron density deficiency.
