Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.544135
Title: Process characterisation of a manufactured living dermal equivalent (ICX-SKN) and use of ultrasound for product improvement
Author: Kee, Jasmin
Awarding Body: Loughborough University
Current Institution: Loughborough University
Date of Award: 2009
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.544135  DOI: Not available
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