NANOMATERIALS IN BIOMEDICAL ENGINEERING

INTRODUCTION

- Materials of size between 1 and 1000 nanometres (10 −9 meter) but is

usually 1—100 nm (nanoscale).
- A natural, incidental or manufactured material containing particles, in an
unbound state or as an aggregate or as an agglomerate and where, for 50
% or more of the particles in the number size distribution, one or more
external dimensions is in the size range 1 nm - 100 nm (EU definition of
2011)

Nanomaterials have extremely small size and can exist in single or fused forms
with spherical, tubular, and irregular shapes.
Nanotechnology exploits benefits of ultrasmall size, enabling the use of
particles to deliver a range of important benefits; this “quantum size” controls the
macroscopic properties of the final material e.g. Small particles are ‘invisible’ ,
thus:
- Transparent Coatings/Films are attainable
- Small particles are very weight efficient:
- Surfaces can be modified with minimal material

The behavior of nanomaterials mainly depends on surface area (as opposed to

the composition itself). High surface area to volume ratio enhances reactivity,
strength and electrical properties., so by designing matter on the nano scale, it is
possible to vary fundamental properties of materials without changing the
chemical composition.

Types of Nanomaterials

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1. Natural nanomaterials
- Organic nanomaterials e.g. viruses, natural colloids, horny materials,
paper, cotton, bone matrix etc
- Natural inorganic nanomaterials examples: clays, opals, cement,
fumed silica etc.

2. Synthetic nanomaterials
- Fullerenes - Graphene (allotrope of carbon) sheets rolled into tubes
or spheres e.g. carbon nanotubes Graphene nanostructures
- Nanoparticles - Inorganic nanomaterials, (e.g. quantum dots,
nanowires and nanorods) have interesting optical and electrical
properties. Nanoparticles are being extensively investigated for
biomedical applications including tissue engineering, drug
delivery, biosensors
- Nanozymes - Nanomaterials with enzyme-like characteristics. They
are an emerging type of artificial enzyme, which can be applied in
bio-sensing, bio-imaging, tumor diagnosis and therapy, anti-
biofouling, etc.

Nanomaterials can further be classified based on:

1. The size
- 3 dimension materials e.g. quantum dots or nanoparticles and
Fullerene. They are formed by tens or hundreds of atoms and can
have different size and shape e.g. fullerene which is formed by
carbon atoms forming a “ball” of nanometer diameter.
- 2 dimension materials e.g. Carbon nanotubes. They are linear
structures that can reach microns of length with nanometric
diameter. They can be single or multiwall.
- 1dmension materials e.g. Graphene and other inorganic layer
materials. Graphene is formed by a layer of a carbon atoms, while
other inorganic layers can be grown to modify the surfaces of bulk
materials
- Nanolayers are a very important class of nanomaterials. Often they
are used to modify the surface of bulk materials.

2. The Phase Composition

- In the nanocomposites - a nanomaterial (nanoparticles,
nanotubes, layers) acts as a filler of a matrix material that in most
cases is a polymer. The nanomaterial contributes to the
nanocomposites new or improved properties (mechanical,
electrical, optical etc.). Another common matrix is the ceramic or the
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 glass (inorganic nanocomposites): the glass is mixed with
nanoparticles to obtain different colors.

Nanomaterials and Nanotechnology in Medicine

Nanoparticles for Biomedical Applications must be biocompatible. The

following examples have been synthesized:
- Magnetic Nanoparticles for Magnetic Resonance Imaging (MRI)
- Thermally blocked Nanoparticles for biodiagnostics
- Nanoparticles for Drug Delivery
- Multifunctional nanoparticles
- Thermosensetive nanoparticles
- Ferrogel for drug delivery

Nanoparticles offer the following in medical applications

i. Fast and more efficient biosensors
ii. Targeted drug delivery to specific cells
iii. Novel cancer therapy and hyperthermia treatments
iv. Magnetic resonance imaging enhancement
v. Single cell study and bio-manipulation
vi. Novel diagnostic tools or early stage detection of diseases

SYNTHESIS OF NANOMATERIALS
The method should exhibit control of size in this range in order to attain
specific characteristics

Approaches

Top-down – Breaking down matter into more basic building blocks. This method
frequently uses chemical or thermal methods. It can also be achieved by
mechanical grinding.

Bottom-up – Building complex systems by combining simple atomic-level

components. Examples include:
- Wet Chemical methods ( top-down &bottom up )
- Sol-gel process methods for creating nanostructures
- Gas Phase methods for creating nanostructures

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Chemical Solution Methods for Nanoparticles synthesis

1. Precipitation
- Homogenous precipitation
- Co-precipitation
- Hydrolysis
- Oxidative hydrolysis
- Reductive precipitation
- Electrochemical reduction

2. Condensation
- Sol-gel technique
- Macro-molecular chemistry

3. Evaporation
- Spray-drying
- Spray-pyrolysis
- Freeze-drying
- Aerosol technique

4. Templates
- Precipitation in microemulsion
- Precipitation in presence of surfactants

5. Others
- Sono-chemical reactions

Nanomaterials can be tailor designed to achieve specific characteristics e.g.

design of tailored magnetic nanoparticles. The following examples are super
paramagnetic and thermally blocked nanoparticles with strong magnetic
response.
- Magnetite (Fe3O4)
- Maghemite (Fe2O3)
- Ferrites (CoFe2O4, ZnFe2O4, MnFe2O4...)
- Iron platinum (FePt), CoPt

Bio-compatibility of nanomaterials can be achieved or improved by surface

functionalization e.g.
- Inorganic: coating with gold, silica, hydroxyappatite, ...
- Organic: Coating with dextran, PVA, PEG, mPEG, ...

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Nanomedicine - Nanotechnology applied medically. It offers
- New breakthroughs in medicine
- Advanced biomedical research tools
- Labels to experiments
- Study of DNA and its component genes
- Diagnostic tests
- In bone implants etc…

Examples of applications

Drug Delivery Methods - Systems that deliver drugs to specific sites

1. Smart Drugs – They attack specific antigens using Immunotoxins that are
protein in nature.

2. Nanocomposite hydrogel systems: Can be applied in thermo therapeutic

process where they releases drugs that are encapsulated on heating. Gold
nanoshells/nanoparticles can be used and the Ideal working wavelengths
of light are infra red i.e 800-1200nm

3. Magnetic Nanoparticles: Drugs are bound to magnetic nanoparticles which

carry drugs to malignant sites with magnetic fields. At the site the drug is
released by enzymatic activity

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Disease Detection
1. Cancer/Virus Detection
Carbon Nanotubes, gold nanoparticles & Nanodots and Nanowires can be used.
Silicon nanowires can be used in Gene Detection

Carbon Nanotubes covered with monoclonal antibodies can be used in cancer

detection. Antibodies for growth factor receptor commonly found in cancer cells
are used.
Antibodies are attached to nanoparticles, nanoparticle antibodies bind to cancer
cells, Colors are reflected when light hits particles. The shapes and sizesof the
nanoparticles affect color

Silicon Nanowires

Similar in use to nanotubes, antibodies attached to wire and current changes

measured. Can be applied to cancer cells and viruses

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2. Gene Detection e.g using silicon nanowire:
This can be applied to detect specific genes. The process involves Nucleic acids
being attached to nanowires to create specific sequences. The sensor capable of
differentiating mutated and non-mutated genes

3. Imaging Techniques
Conventional Techniques such as X-ray, MRI, Fluoroscopy CAT scan show limited
detail. Also it is difficult to track movement

Imaging Applications of nanopartilces

- Molecular Tracking:
- Use Quantum Dots as labels
- Dots attached to molecules before injection
- Fluoroscopy used to track movement
- Colors from dots seen and imaged
- Tracking blood flow:
- Tag proteins of cells with gold nanoparticles
- View process of angiogenesis
- Important for cancer detection and imaging

Concerns about use of nanoparticles in Medicine

- Negative biological side-effects:
- Toxicity of quantum nanodots
- Effects on living organisms not well known

Note:
- Gold nanoparticles safer:
- Biologically inert
- Won’t interact with other chemicals