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|Title: ||Process characterisation of a manufactured living dermal equivalent (ICX-SKN) and use of ultrasound for product improvement|
|Authors: ||Kee, Jasmin|
|Issue Date: ||2009|
|Publisher: ||© Jasmin Kee|
|Abstract: ||The routine use of regenerative medicine products in patients requires cost-effective
manufacturing processes and products that meet business and customer needs. The
dermal skin substitute lCX-SKN, produced by lntercytex for the treatment of acute
wounds, completed Phase I clinical trials in 2007. lCX-SKN is manufactured by
seeding neonatal human dermal fibroblasts in a fibrin matrix and culturing for 49 days
to form a collagen matrix synthesised by the cells.
The results captured by this thesis demonstrate an integrated engineering and biological
science approach to improve the current lCX-SKN process model and identify methods
for process and product improvement. Measurement of the changes in the biochemical,
mechanical and physical properties of lCX-SKN during the 49 day manufacturing
period produced an improved four-phase process model describing cell proliferation,
matrix compaction, fibrin degradation, collagen synthesis and matrix remodelling.
Ultrasound was identified as a scalable form of mechanical stimulation for product
improvement particularly as it does not require physical coupling to the constructs. A
custom-built ultrasound device was used to investigate the effect of ultrasound on
collagen synthesis and mechanical properties. A design of experiments showed that
different combinations of ultrasound intensity (0.5-2.5W/cm2
), duty cycle (5-80%) and
duration (5-30minutes) affected the shear storage modulus (G') and collagen content.
However, a significant effect on G' only resulted from combinations of duty cycle and
duration. Further experiments to improve the properties of the construct, using
0.5W/cm2 intensity, 50% duty cycle and 14 minute duration resulted in a 73% increase
in G' primarily through increased collagen deposition.
The results showed that further work is required to minimise process variation through
control of the input raw materials. Optimisation of the fibrin matrix and diffusion of the
culture media were identified as key areas to improve manufacturing cost-effectiveness.
Enhanced understanding of the physical and molecular mechanisms by which
ultrasound elicits cell responses will enable further optimisation of the ultrasound
process for product improvement.|
|Description: ||A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of Doctor of Philosophy of Loughborough University.|
|Appears in Collections:||PhD Theses (Mechanical, Electrical and Manufacturing Engineering)|
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