Biomaterial Physics

University of Manchester
Lecturer:
Prof. Henggui Zhang

Author:
John Scott

February 2016

Contents
1 Introduction
1.1 What is a Biomaterial? . . .
1.2 Growing Tissues . . . . . . .
1.3 Biosensors . . . . . . . . . .
1.4 Interdisciplinarity . . . . . .
1.4.1 Physics of Materials
1.4.2 Biochemistry . . . .
1.4.3 Toxicology . . . . . .
1.4.4 Biocompatability . .
1.4.5 Healing . . . . . . .
1.4.6 Anatomy . . . . . . .
1.5 Reliability of Biomaterials .
1.6 Polymers . . . . . . . . . . .
2 Biology and Biochemistry
2.1 Atoms and Ions . . . . . .
2.2 Molecules . . . . . . . . .
2.2.1 Water . . . . . . .
2.2.2 Amino Acids . . .
2.2.3 Zwitterions . . . .
2.2.4 Monosaccharides .
2.3 Biological Macromolecules
2.3.1 Lipids . . . . . . .
2.3.2 Proteins . . . . . .

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Chapter 1
Introduction
Biomaterials are an emerging industry, with the potential for multi-billion pound investments. The
reason for this is the needs of millions of people suffering end-stage organ or tissue failure annually.
Some examples of biomaterials include:
Total Implanted Devices
Coronary stents
Shoulder, hip etc. replacements
Surgical stitches
Partially Implanted Devices
Temporary skin grafts
Tooth roots
Totally External Devices
Biosensors
Blood filtration
Contact lenses

1.1

What is a Biomaterial?

Williams (1987) defines a biomaterial as a non-viable material used in a medical device, intended
to interact with biological system. As such, the most important property of biomaterials is BIOCOMPATABILITY. Biocompatability is the ability of a material to perform with an appropriate
host response in a specific application.
It is worth defining some terms before diving into the course.
Definition A transplant is the movement of an organ from donor to recipient.
Definition A tissue engineering substrate is a material used to produce new tissues for direct reimplantation (which reduces animal experimentation in labs).
Definition Natural biomaterials are living tissues or natural materials that are prepared synthetically. Examples of these include polymers, metals, semiconductor materials and ceramics.
2

1.2

Growing Tissues

In 2013 a British businessman lost his nose to skin cancer and grew a replacement on his arm. The
process behind this was as follows:
1. Photos and CT (computer tomography) scans were used to create a glass mould of the old
nose.
2. The mould was given a synthetic honeycomb-type covering. The glass mould was then removed
and stem cells, which were extracted from the patients bone marrow and multiplied in the lab,
were sprayed over the honeycomb framework.
3. The framework was placed into a bioreactor - a rotating jar packed with nutrients and water,
in order to encourage the stem cells to reproduce and form cartilage.
4. A balloon was placed under the skin of the forearm of the patient, which was inflated a small
amount daily in order to stretch the skin.
5. After three months the balloon was removed and replaced with the fledging nose, which acquires
nerves, blood vessels and skin.
6. Three months later the nose is removed from the arm and appended to the face.

1.3

Biosensors

A biosensor is a device that carries out some sensing function on a biological system. This can
simply be a thermomemter or blood pressure monitor. More recently it refers to a device which uses
a biological agent to carry out the sensing for medical, biological and non-biological applications.

1.4

Interdisciplinarity

Biomaterials draws upon many areas of research to investigate the best ways in which to address
problem-solving.

1.4.1

Physics of Materials

We need to know the purpose of the material according to each device in order to enhance its
properties. The durability of the material is imporant; a catheter will last a few days, whereas a hip
prosthesis may last over 10 years.

1.4.2

Biochemistry

We must know how cells etc. interact with biomaterials and devices at a molecular level.

1.4.3

Toxicology

Biomaterials should not be toxic unless required to be so (e.g. smart drug dlivery which can specifically target cancer cells). This applies not only to biomaterials themselves, but anything that may
leach out in vivo (within the living) must be considered for its toxicity.

1.4.4

Biocompatability

Biocompatability is difficult to define and virtually impossible to measure, e.g. a patient with a
titanium dental implant may be fine, whereas titanium can clause blood clotting in another patient.

1.4.5

Healing

There are specific responses to wounds and to the blood vessels. Other responses, such as inflammation, reaction to foreign bodies etc. must be considered.

1.4.6

Anatomy

Shape, size and biocompatability must be considered for each device, dependent on where in the
body the device will be placed.

1.5

Reliability of Biomaterials

If we assign a numerical value, f , to the probability of an implant failure, then the reliability, r, may
be expressed as
r = 1 f.
If there are multiple factors of failure then the total reliability, rt , is given by
rt = r1 r2 ... rN .

1.6

Polymers

Pilors injured by polymethyl methacrylate (PMMA) did not suffer chronic (recurring) reactions to
the presence of PMMA fragments in the body, so it became widely used as a corneal and skull
fragment replacement material.

Chapter 2
Biology and Biochemistry
2.1

Atoms and Ions

Living systems are similar to any other mechanical system, in that there is a requirement of energy
for processes to undergo and typically happen at a non-relativistic rate. Life consists of series of
biophysical (movement of ions across a semi-permeable membrane within biological molecules) and
biochemical reactions.
Within and surrounding cells there are free ions, which allows the transfer of signals by changing ionic concentrations of K+ , Ca2+ and Na+ across cell membranes. The evolutionary origin of this
comes from the fact that all living organisms on Earth derive from the sea, thus are reliant upon the
salts present in the water.

2.2

Molecules

In biology the main molecular groups of interest are those which constitute the macromolecules,
which include proteins, fats, carbohydrates, nucleic acids, vitamins, toxins etc. These are subdivided
into their constituent MONOMERS (unit molecules/cells) - amino acids, simple sugars, fatty acids,
glycerol and nucleic acid bases. However, probably the most important molecule for life is water,
which has many functions in biological processes which are not yet fully understood.

2.2.1

Water

Water has an uneven distribution of electron density across the molecule, resulting in a partially
negative ( ) charge near the oxygen and a partially positive ( + ) charge near the hydrogens. The
small electrostatic charges then form intermolecular hydrogen bonds, which are stronger than van
der Waals forces but weaker than ionic or covalent bonds. In order to form hydrogen bonds, the
hydrogen must be covalently bonded to another electronegative atom. These bonds are not specific
to water or inorganic molecules, as it also occurs in biological molecules, such as DNA. In the case
of water, the hydrogen bonding means that the molecules tend to orient themselves in a particular
way with respect to its neighbours.
The polarity of water also allows it to dissolve other polar molecules, such as salts (e.g. NaCl),
by using the electrostatic force of the negative oxygen to attract the negative polar atom/molecule
and the negative hydrogens to attract the positive polar atom/molecule. As such, water molecules
separate and surround charged groups, producing a solution (polar molecule has dissolved).

Hydrophobicity and Hydrophilicity

Hydrophobic (scared of water) compounds do not bond well with water. As a result, these
molecules tend to cluster in water. Examples of these include compounds containing a large number
of methane group (CH2 ) or phenyl rings (benzene; C6 H6 ).
Hydrophilic (attracted to water) compounds bonds very well with water. Examples of these are
compounds containing a large number of alcohol, carboxyl and amine groups or any group which
carries charge (polar).

2.2.2

Amino Acids

The general form of an amino acid is a central -carbon atom which is covalently bonded to an amine
group (NH2 ) and a carboxyl group (COOH), with an extra H bond and the rest of the molecule,
otherwise known as the side chain or R group, as shown below: The R group may vary in size, shape,
H
R

COOH

NH2
charge, hydrogen-bonding capacity and chemical reactivity.
There are 20 naturally occurring amino acids that form the basis of all life found on Earth. All
proteins are comprised from this group of amino acids.
Stereoisomers
Stereoisomers, also known as spatial isomers, are molecules that have the same molecular formula
and constitution (sequence of bonded atoms/groups), but differe in three-dimensional orientations in
space, e.g. mirror images. These stereoisomers rotate polarised light in different directions, depending
on whether the molecule is left-handed (L; laevorotatory) or right-handed (D; dextrorotatory). Only
L-isomers are constituents of proteins.

2.2.3

Zwitterions

A zwitterion is a molecule that has equal positive and negative charges, such that it is overall
electrically-neutral. Amino acids may form zwitterions by either gaining a hydrogen molecule on
the amine group, forming a positive ammonia molecule, or losing a hydrogen, forming a negative
carboxylic acid group. The zwitterion formed depends on whether the solution is hydrogen rich
(acid) or hydrogen poor (basic/alkali). The hydrogen concentration dictates the pH of the solution,
which is given by
pH = log10 (H+ ).
The formation of zwitterions is an important feature of pH within the body as acidic conditions can
lead to blood clotting within the arteries.

2.2.4

Monosaccharides

A saccharide is often used as a synonym for sugars, which belong to a class of organic compounds
called aldehydes and ketones. A monosaccharide is the most basic unit of carbohydrates, which
6

cannot be hydrolised to simpler compounds. They have the general molecular formula Cn H2n On .
Aldehydes have a characteristic C=O double bond at the end of the molecule, comprising the formyl
(R-CHO) group, with the simplest case being formaldehyde (H-CHO). Ketones, however, contain
the C=O double bond along the molecule, resulting in a R-CO-R form of the molecule.
Fatty acids acids consist of long chains of hydrocarbons, which are terminated by a carboxyl group
(COOH).
Glycerol is terminated by an alcohol group (OH).

2.3
2.3.1

Biological Macromolecules
Lipids

Lipids are a group of naturally occurring molecules that include fats, waxes and fat-soluble vitamins
(e.g. A, D, E, K). Phospholipids are a class of lipids that are a major component of biological
membranes. On top of this, other derivatives serve as hormones or intracellular messengers, as
well as fuel storage. These phospholipids have an AMPHIPHILIC characteristic, in that it is both
hydrophobic and hydrophilic, which manifests itself as a hydrophilic phosphate head and hydrophobic
tail. Phospholipids therefore form lipid bilayers with the heads in contact with the water and tails
internal to the layers.

2.3.2

Proteins

Proteins are the most important class of macromolecule in biology. They are polymers (chains of
monomers) of amino acids, which form peptide bonds (covalent bonds between amino acids) to link
together.
H
H3 N+

R1

+ H3 N+

R1

H3 N+

R2

H
N

R2

O
C

+ H2 O
O

The sequence of amino acids in a protein is called the PRIMARY STRUCTURE. The peptide bonds
lie in the same plane and define the polypeptide backbone of the protein.
The SECONDARY STRUCTURE is governed by the rotations or folding of the polypeptide chains.
The two most common types of folding are -helix and -pleated sheet.
7