About the Project
Peripheral nerve injuries through trauma, and sometimes surgery, result in over 300,000 cases each year in the EU. In contrast to the central nervous system, peripheral nerves have some ability to repair. Individuals who sustain injury with no loss of tissue can be treated by directly suturing proximal and distal ends together. However, end-to-end repair is not possible when there is loss of significant nerve tissue. Injuries greater than 1-2 cm usually require autografting, but have poor functional outcome. Patients typically lose motor and/or sensory function, with morbidity at the donor site. Implantable nerve guide conduits (NGCs) are used to support short gap injuries. A major challenge is to increase regeneration distance and address longer critical gap distances of 10-20 mm. Thus, advanced NGCs are needed for critical gap repair. In this PhD the student will aim to develop NGCs for critical gap repair using a family of FDA approved natural polymers, Polyhydroxyalkanoates (PHAs), that are produced using bacterial fermentation. The Roy lab has already proven the neuro-regenerative properties of PHAs1 and hollow PHA blend based NGCs have exhibited excellent nerve repair in vivo rat models. Hence, for critical gap repair, the PHA blend based NGCs will be further functionalised using physical and biological cues. Introduction of internal nano/micro topography using PHAs and other natural polymers and controlled release of active factors will be explored. A variety of processing methods including dip moulding, 3D-printing, melt/solution electrospinning will be used for the production of the final product. The prototype NGCs will be evaluated using a
dorsal root ganglion 3D in vitro chick model and mouse/rat in vivo models.
The project will be linked to the University of Sheffield Neuroscience Institute (https://www.sheffield.ac.uk/neuroscience-institute/home) led by Professor Dame Pamela Shaw. The Institute brings together internationally recognised expertise in medicine, science and engineering. Professor John Haycock, Dr Fred Clayssens and Professor Fiona Boissonade, joint co-supervisors, are active members within this Institute. Prof. Stefano Geuna, University of Torino, Italy, will also be part of the supervisory team.
The selected PhD student will be registered in Materials Science & Engineering, University of Sheffield and also be part of the Neuroscience Institute and will benefit from the resources linked to both, with the opportunity to participate in respective seminars and meetings.
Prof. Roy will be joining the University of Sheffield in September but you can see her profile on the University of Westminster website.
Funding Notes
This studentship will pay tuition fees in full and a stipend for living expenses for 3.5 years. This stipend will be at the RCUK minimum which for the 2019/20 academic year is £15,009pa.
Funding covers home tuition fees and annual maintenance payments of at least the Research Council minimum for eligible UK and EU applicants. EU nationals must have lived in the UK for 3 years prior to the start of the programme to be eligible for a full award (fees and stipend).
References
Recent publications by supervisors that are relevant to the project:
1. Lorena R. Lizarraga-Valderrama, Rinat Nigmatullin, Caroline Taylor, John W. Haycock, Frederik Claeyssens, Jonathan Knowles, Ipsita Roy ‘Nerve Tissue Engineering using blends of Polyhydroxyalkanoates for peripheral nerve regeneration.’2015 Engineering in Life Sciences - Special issue: SMART POLYMERS & BIOTECHNOLOGY (invited paper)- 15(6) 612-621
2. Barbara Lukasiewicz, Pooja Basnett, Rinat Nigmatullin, Rupy Matharu, Jonathan C. Knowles and Ipsita Roy 2018, Binary Polyhydroxyalkanoate Systems for Soft Tissue Engineering, Acta Biomaterialia 71: 225-234.
3. Pooja Basnett, Elena Marcello, Barbara Lukasiewicz, Bijal Panchal, Rinat Nigmatullin, Jonathan C. Knowles, Ipsita Roy 2018, Biosynthesis and characterization of a novel, biocompatible medium chain length polyhydroxyalkanoate by Pseudomonas mendocina CH50 using coconut oil as the carbon source. Journal of Materials Science: Materials in Medicine, Nov 30;29(12):179. doi: 10.1007/s10856-018-6183-9.
4. R. Rai, D. M. Yunos , A. R. Boccaccini, J. C. Knowles, I. A. Barker, S. M. Howdle, G. D. Tredwell , T. Keshavarz and I. Roy “Poly-3-hydroxyoctanoate P(3HO), a unique medium chain length polyhydroxyalkanoate homopolymer from Pseudomonas mendocina” 2011 Biomacromolecules, 12 (6), pp 2126–2136.
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