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Designing tomorrow’s implants
Biomaterials Team
Elzbieta Gurdak, Mike Shaw, Nilofar Faruqui and Paul Tomlins
NPL is developing a new method for assessing the
biocompatibility of potential implant materials. Our approach is
to monitor the way in which cells interact with material surfaces
by quantitatively measuring changes in their shape over time.
Cells in suspension are close to spherical. When they attach to
a surface, cells undergo a substantial change in shape, becoming
progressively more flattened and forming arm-like structures
which join together to create communication links between
adjacent cells.
What are the important surface characteristics ?
All aspects of the surface i.e. topography,
chemical fingerprint, and/or crystal type and
orientation play an important role in affecting
the response of cells, which represents a
significant manufacturing challenge in its
own right. Care also needs to be taken to
understand in detail the value of information
provided by the analytical tools used to
measure surface topography, chemistry, etc.
An additional challenge is that local
changes in, for example, surface chemistry
and crystallographic orientation combine
with variations in surface roughness
making it difficult to independently assess
which factors have the most influence
on cell behaviour. The adjacent images
show surfaces with regular pattern and
random texture.
What happens when a cell comes into contact with a surface?
Cells that come into contact with a surface do so through an adsorbed
layer of proteins. These proteins are present in the blood and adsorb
on the surface within a matter of a few seconds. Biocompatibility is,
at least in part, directed by the composition and conformation of the
proteins that form this layer. The impact of the information that the
Attachment
cells detect can trigger an immune response; i.e. the body rejects the
implant or, at the other extreme, cells will attach to it and integrate
it into the body. The process of single cells beginning to attach to a
surface where they form communication links with other cells and
eventually form a tissue is shown below.
Spreading
Proliferation
Tissue formation
How do you quantify cell interaction with surfaces?
We can now track the cell
attachment stage using a
combination of laser scanning
confocal microscopy and
fluorescent dyes. The confocal
microscope can be used to
capture a 3-dimensional image
of a cell at a given time. This
image is then processed to
reliably determine where its
boundaries lie. The adjacent
images show two surfaces, one
of which is more biocompatible
than the other. Cells on the less
biocompatible surface flatten
more slowly than those on
more biocompatible surface.
This behaviour is quantified in
plots showing cell thickness
changes at different times.
Glass uncoated (“less biocompatible”)
Fibronectin coated glass (“more biocompatible”)
15 mins
30 mins
What next?
This novel approach will need to be validated before it can be adopted by the medical devices sector by comparing measurements made with
other complementary techniques and real-life findings.