CHEMBIO 3BM3 | LIFESCI 3BM3

Lecture 1

2021/1/11

Lecture will start @ 10:30am

© M. Brook 2016-19
 Implantable Biomaterials
CHEMBIO 3BM3 | LIFESCI 3BM3
Ryan Wylie
wylier@mcmaster.ca
TA: Alex Jesmer, jesmera@mcmaster.ca
(PLEASE PUT 3BM3 in SUBJECT LINE of any emails)

© M. Brook 2016-19
Objectives
• Chemists, Biologists, Life Scientists and Engineers can communicate with each other (at an appropriate
level)

• Learn the basic properties of biomaterials used for implantation

• Establishing the criteria for success
• Functional
• Chemical
• Mechanical
• Biological
• Aesthetic
• Choosing the best material
• Controlling the Surface/interface
• Design the device
• What goes wrong?
•Making your case to regulators

© M. Brook 2016-19
 Marks
• 1 midterm test – February 11th, 2021 in class 20%
(OPTIONAL!, weight goes to final exam if not
submitted)

• 1 minor assignments Feb 3rd, 2021 15% (OPTIONAL!,

weight goes to final exam if not submitted)

• 1 major assignment – April 8-12th 2021 25%

• Final exam 2 h - 40%

© M. Brook 2016-19
 The Plan
• Lectures on biomaterial design, selection and characterization
• Special guest lectures
• Cover emerging research in biomaterials

• Midterm mostly on background

• Assignment 1: Demonstrate how a current clinically used medical device was
approved using biomaterial design. Why did the device succeed? What
material biological properties were key? Details will be provided in the Teams
Class Notebook.

• Assignment 2 group presentation: Propose a new medical device for an

unmet need. Cover the scientific and path to device approval.
• Mark is a combination of: my mark, TA mark, audience mark and YOU MARK
YOUR OWN GROUP MEMBERS!

© M. Brook 2016-19
Guest Lectures (subject to change)
• Mike Cooke Local drug delivery and market approval
• Michael Thompson Mechanical properties of Materials
• Heather Sheardown Intraocular lenses
• Grandfield Lab Orthopedic implants
• Iqbal Jaffer Cardiac Devices
• Mike Brook Silicone implants
• Others?

•
NOTE: From time to time I (and others) will show videos that include operation, insertion/removal of biomedical implants.

© M. Brook 2016-19
What is a Medical Device?
• • Any instrument, apparatus, appliance, material or other
article,
• including software, whether used alone or in combination,
• intended by the manufacturer to be used for human beings
• solely or principally for the following purposes:
• Diagnosis, prevention, monitoring, treatment or alleviation of
disease;
• Diagnosis, monitoring, treatment, alleviation of or compensation
for an injury or handicap;
• Investigation, replacement or modification of the anatomy or of a
physiological process;
• Control of conception – may involve actives delivery.

© M. Brook 2016-19
Definitions - Biomaterials
• Biomaterials are materials (synthetic and natural; solid and sometimes
liquid) that are used in medical devices or in contact with biological
systems.

• Examples include:
• Polymers – Hydrogels
• Ceramics
• Metals Composites
• Living cells
• Tissues

• Implantable Biomaterials (this course): Surgical implantation and non-

intravenous injections.

© M. Brook 2016-19
Biomaterials development – how to wrap your head around it all?
• Biomaterial science is cross-disciplinary and application oriented. The goal is to develop a
material that can replace, prevent, enhance or detect a biological event. Therefore, the
application will be the primary determinant.

Identify biological problem (unmet need)

Type of Application Needed bioactivity

• Drug delivery • Adaptive immune response (vaccine)
• Intracellular delivery • Selective killing (cancer)
• Tissue /function replacement • Up/down regulation of pathways
• Tissue Engineering / Regenerative • Long term replace of function (hip joint)
medicine • Detect pathogens
• Sensors • Regenerate damaged tissue (heart)
• Among many others • Among many others

Guide selection of biomaterial by optimizing

• Chemical,
• Mechanical, and
• Biological properties
• While minimizing side effects (infection, foreign body
responses, nonspecific binding)
• Production, cost/benefit ratio
Biomaterial Science 4th edition
 CHEMBIO 3BM3 | LIFESCI 3BM3

Lecture 2

2021/1/13

Lecture will start @ 10:30am

© M. Brook 2016-19
Example: mRNA vaccines (BioNTech and Moderna)
BioNTech’s BNT162b2 vaccine 

https://www.ft.com/content/74e41528-80c3-4b0f-b343-be43d90f0311

• Why were mRNA vaccines developed? What advantages do they have

over traditional vaccines.
• Problems: mRNA penetration into cells, and mRNA stability after injection
 mRNA vaccine
mechanism

Nature Reviews Drug Discovery volume 17, pages261–279(2018)

© M. Brook 2016-19
 What is the biological problem?
• Need to achieve a significant adaptive immune response from an immunogen
of SARS-CoV-2.

What are the biological/clinical requires?

Need to be fast!

Need to get mRNA into antigen expressing cells.

What are the biomaterial design criteria?

https://doi.org/10.1039/C4NR00018H
© M. Brook 2016-19
Platforms for mRNA
delivery
 What categories do mRNA SARS-CoV-2 vaccines fit into?

Biomaterial Science 4th edition

 CHEMBIO 3BM3 | LIFESCI 3BM3

Lecture 3

2021/1/13

Lecture will start @ 10:30am

© M. Brook 2016-19
Biomaterial-tissue interface/response is extremely important
Biomaterial-tissue response:
• form of biologic integration controlled by surface of material, or
• engineered to trigger encapsulation/foreign body response.

First,
What is a tissue? What are the categories of tissue? What is the difference between tissue
and organs?

• Tissue is a collection of similar specialized cells serving the same general function
with the same extracellular matrix (ECM).

• Organs are 2 or more tissues that combine to execute a more complex function.

• The ECM is non-cellular components of tissues and organs that provide structural
support to cells as well as biochemical and biomechanical signals. Cells can detect
changes in their biochemical and biomechanical environment. The dominant
component of the ECM is collagen (remember there are multiple types of collagen.
Biomaterial-tissue interface/response is extremely important
Biomaterial-tissue response:
• form of biologic integration controlled by surface chemistry, or
• engineered to trigger encapsulation/foreign body response.
First,
What is a tissue? What are the categories of tissue? What is the difference between tissue
and organs?

Layers with skin, blood vessels, organs

Cartilage

Muscle and support cells

Neurons andneuroglia

https://toxtutor.nlm.nih.gov/08-004.html
Cellular activities will we usually need to consider

Cellular activities/functions that represent a complete (usually quantified) sequence. For our
purposes, these are processed that we can quantify to help identify tissue-biomaterial responses.

1. Proliferation (mitosis)
2. Cell attachment
3. Protein synthesis and deposition (ECM structural proteins, signalling molecules, enzymes)
4. Exocytosis, degranulation (opposite of endocytosis). Release of reactive molecules.
5. Endocytosis (cellular ingestion of particles)
6. Migration
7. Contraction

More complex activities

1. Inflammation
2. Macrophage activation
3. Foreign body response
4. Immune responses
Biomaterial properties/concepts that will be recurring throughout
the course
Note: Not all properties need to be studied for all biomaterials and
applications, it will depend on the biological environment and bioactivity.

1) Permanent or Absorbable
Positive response Adverse response

• Contraction (common in breast

Permanent Biomaterials implants, how to avoid?)
(permanent or semi- • Reaction to particles (form
Tissue attachment biomaterial; “small particle
permanent implants; e.g. hip
disease”)
and knee replacement)
• Tissue
destruction/inflammation

Absorbable (degradable) • Healing/repair of tissue • Tissue

biomaterials (more common
in drug delivery and tissue
engineering)
• Execute wanted biological destruction/inflammation
response (e.g. pain • Systemic and/or immunological
management, cancer cell responses
killing)
Biomaterial properties/concepts that will be recurring throughout
the course
Note: Not all properties need to be studied for all biomaterials and
applications, it will depend on the biological environment and bioactivity.

2) Bulk versus surface properties (equally important)

Surface properties are anything to do with the surface of the biomaterial. For example, protein adsorption
(nonspecific binding) to the surface, surface coatings/chemistries, among many others

Bulk properties are everything other than surface properties. For example, mechanical properties (strength,
modulus of elasticity, fracture), temperature transitions (LCST)

What about biomaterial erosion? Surface or Bulk?

CHEMBIO 3BM3 | LIFESCI 3BM3

Lecture 4

2021/1/18

Lecture will start @ 10:30am

Biomaterial properties/concepts that will be recurring throughout
the course
Note: Not all properties need to be studied for all biomaterials and
applications, it will depend on the biological environment and bioactivity.

3) Bulk properties of biomaterials

For any biomedical material, bulk properties must meet mechanical/physical needs for the application over
the desired timeframe.

Where do bulk properties come from? Why do metals, ceramics and polymers have different bulk
properties?
Interatomic or intermolecular forces. Differences in bonding determine bulk properties.

What are metals, ceramics and polymers? How does their binding differ?
Biomaterial properties/concepts that will be recurring throughout
the course
Note: Not all properties need to be studied for all biomaterials and
applications, it will depend on the biological environment and bioactivity.

4) Determining characteristic values for a biomaterial under mechanical load

To quantify and compare biomaterials we must have reproducible tests under controlled conditions. We
test materials until a “breaking point” to extract values.

For example, stress and strain are commonly measured mechanical variables (they are not properties of
material). Although stresses that result in structural change (e.g. yielding or breaking) are properties.

We will discuss mechanical variables/properties such as:

• Strength
• Elasticity
• Fracture mechanics
Biomaterial properties/concepts that will be recurring throughout
the course
Note: Not all properties need to be studied for all biomaterials and
applications, it will depend on the biological environment and bioactivity.

5) Surface properties and characterization

Atoms and molecules on the biomaterial surface have special reactivity and direct biological responses.

Surfaces are at the interface with tissue. Surfaces drive MANY biomaterial induced biological responses.

For most biomaterials, the surface structure communicates/transduces the biomaterials structural makeup
to influence the response of proteins, cell and organism. The tissue reads the surface and responds
accordingly (positively or negatively).

So, it is important to understand surface-driven biointeractions.

Problem: So many variables, hard to know what to focus on for each material.
Biomaterial properties/concepts that will be recurring throughout
the course
Note: Not all properties need to be studied for all biomaterials and
applications, it will depend on the biological environment and bioactivity.

5) Surface properties and characterization

Biomaterial Science 4th edition

What techniques can we use?

How deep does a surface go?

What surface properties are we interested in?

roughness, patterns, wettability, surface

mobility, chemical composition, electrical charge, crystallinity,
modulus, and heterogeneity to biological reaction
Biomaterial properties/concepts that will be recurring throughout
the course
Note: Not all properties need to be studied for all biomaterials and
applications, it will depend on the biological environment and bioactivity.

5) Surface properties and characterization

What techniques can we use?

We will discuss some of these during

the course

Biomaterial Science 4th edition

Biomaterial properties/concepts that will be recurring throughout
the course
Note: Not all properties need to be studied for all biomaterials and
applications, it will depend on the biological environment and bioactivity.

5) Surface properties and characterization

What techniques can we use?

We will primarily focus on

the modification of
surfaces, not technique
development.

Biomaterial Science 4th edition

Biomaterial properties/concepts that will be recurring throughout
the course Summary

Primary types of biomaterials Types of tissues Biomaterial properties can be divided into
• Polymers • Connective bulk and surface
• Metals • Muscle
• Ceramics • Nerve Surface of the biomaterial is unique from the
• Composites • Epithelia bulk and “communicates” with the
surrounding biological environment
Biological responses
1. Proliferation (mitosis) Biomaterial are designed to be permanent or
2. Cell attachment absorbable (degradable)
3. Protein synthesis and deposition (ECM structural proteins, signalling molecules, enzymes)
4. Exocytosis, degranulation (opposite of endocytosis). Release of reactive molecules.
5. Endocytosis (cellular ingestion of particles)
6. Migration
7. Contraction

More complex activities

1. Inflammation
2. Macrophage activation
3. Foreign body response
4. Immune responses
 Biomaterial
Surface
Bulk:
• Strength
• Modulus of
elasticity Seconds Hundreds of days
• Fracture mechanics nanometers mm

TISSUE

Cell response Cell-cell interactions Tissue remodeling

ECM proteins
Cytokines
Bulk or surface: Enzymes
• Wear
• Corrosion
• Degradation
• Leaching
Protein adsorption, Particle leaching, ion release
Polymers: Largest class of material used in medicine
Common Applications: orthopedics, dental, hard and soft tissue Polymer molecular architecture,
replacements, drug delivery, and cardiovascular devices. molecular mass, and chemical
composition are directly related to
Major types of applications: the physical and chemical
• Hydrogels (drug and cell delivery) properties
• Nano and micro-particles for drug delivery or specific biological functions.
• Coatings for surfaces on implants (e.g. low-fouling surfaces)

Wednesday – Dr. Mike Cooke – CEO AmacaThera:

• Hydrogels for local drug delivery
• Polymers with thermal transitions
• Drug dissolution
Understanding structure-property relationships  engineer a polymer system for a specific need
Polymers: Largest class of material used in medicine
Common Applications: orthopedics, dental, hard and soft tissue Polymer molecular architecture,
replacements, drug delivery, and cardiovascular devices. molecular mass, and chemical
composition are directly related to
Major types of applications: the physical and chemical
• Hydrogels (drug and cell delivery) properties
• Nano and micro-particles for drug delivery or specific biological functions.
• Coatings for surfaces on implants (e.g. low-fouling surfaces)

Understanding structure-property relationships  engineer a polymer system for a specific need

Polymers Architectures and polymer composition
Copolymers and chemical composition:
• Random copolymers
• Block copolymers

How do you determine chemical composition?

What about reactivity ratios?

Degree of polymerization: Number of monomer repeat units

in each polymer chain

For homopolymer: Mn = M0 × DP, where Mn is the number

average molecular mass and M0 is the molecular mass (or
formal weight) of the monomer unit
Mn is the total weight of the sample divided by the number of
molecules in the sample. Mn = ∑Ni●Mi / ∑Ni

Why do we use averages? What is weight average molecular

weight (MW)?
 Polymer average molecular weights and dispersity
Generally, higher average molecular mass will result in
stronger polymeric materials (with some exceptions) and
greater viscosity, which hinders processing.
Average
number

Average
weight

How do you experimentally characterize molecular weights?

What polymers have a dispersity of 1?

Tacticity of polymer
Relating chemical properties to physical behaviour

Rubbery or glassy state: Polymers exist as random coils in an

• chain stiffness, amorphous structure with chain entanglement
• chain composition or polarity,
• Chain architecture or regularity, and Semicrystalline state: Polymers arranged in highly organized
• molecular mass crystalline domains.
Relating chemical properties to physical behaviour (linear)

Polymeric materials are held together by secondary

interactions , often weaker than other types of biomaterials.

• modulus (a measurement of material stiffness),

• tensile strength (the stress at failure), and
• percent elongation (the amount of deformation at failure)

What happens as the

temperature approaches the
Tg?

Room temperature
Relating chemical properties to physical behaviour
Crosslinking (between polymer chains)
Crystallinity
Copolymers

Block or graft copolymers

 Backbone rotation!

• backbone flexibility,
• pendant group structure and polarity,
• main chain symmetry and polarity
Polymers and water

Polar and electrostatic interactions

What about polymers like PEG?

How do we control bulk polymer-water interactions?
• Ratio of hydrophilic to hydrophobic monomers
• Crystalline regions
• Crosslinking degree

How do we control surface polymer-water interactions?

• coatings
Relating chemical properties to physical behaviour

Polymers can be biodegradable or biostable

For most degradable polymers, degradation occurs by hydrolysis

Consider the bonds in the backbone, common bonds are:

• Carbon-Carbon
• Amides
• Esters