Prof F M Boissonade, Prof J Haycock, Dr S Atkins
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
About the Project
There are 300,000 peripheral nerve injuries per year in Europe (1/1,000 population) giving rise to substantial disability and often the development of chronic pain. Nerve regeneration is particularly poor where there is a gap in the injured nerve, preventing repair by anastomosis of the injured nerve stumps. In this situation, repair with a graft from the patient’s own nerves (an autologous graft) is not ideal as it results in loss of function (and chronic pain) arising from the donor site, and may be followed by a disappointing outcome. The
bioengineering challenge is to create an effective conduit to guide nerve regrowth that will promote functional outcomes better than those achieved by autologous nerve grafts. In Sheffield we have developed an interdisciplinary team with unique capability for implementing a critical path in medical device design, from biomaterials synthesis and fabrication, through neural cell testing, in-vivo evaluation and clinical trial.
A recent proof-of- concept study [1] demonstrates our ability to manufacture a nerve guidance conduit using a 3D printing process with micrometre resolution (microstereolithography). These nerve guidance conduits can support regeneration across short-gap injuries, equivalent to that achieved with a nerve graft. The overall aim of this project is to design, manufacture and evaluate a new class of biodegradable nerve conduits with the ability to promote peripheral nerve regeneration over long-gap injuries, as well as, or better than, an
autologous nerve graft.
The specific objectives are to establish:
i) the optimal design (material and structure) of the microfibre conduit;
ii) whether optimally designed conduits can perform better than autologous nerve grafts;
iii) whether our optimally designed conduits populated with antifibrotic agents or support cells (in the form of Schwann or stem cells) perform better than empty conduits.
The project will use microstereolithography to construct customised biodegradable conduits made from polycaprolactone (an FDA-approved material) or poly-glycerol sebacate methacrylate (a novel formulation that has excellent mechanical properties for nerve repair, can be sutured and is photocurable). Comparisons will be made between nerve grafts, empty conduits and those with a range of different internal structures. We will also determine the effect of including antifibrotic agents. Our previous studies show that these agents can enhance nerve regeneration following nerve repair with end-to- end anastomosis [2–4]. In addition we will establish whether the addition of cells (Schwann cells or stem cells) can further facilitate nerve growth. Cells will be cultured using our established high efficiency techniques [5, 6]. Nerve regeneration will be assessed using methodologies that are well established in our laboratories. These include tracing individual axons through the conduits to assess regeneration at the level of the individual axon [1, 4], electrophysiological recordings of compound action potentials and functional assessment of outcome using walking track analysis [2, 3]
Enquiries:
Interested candidates should in the first instance contact Professor Fiona Boissonade ([Email Address Removed])
How to Apply:
Please complete a University Postgraduate Research Application form available here: http://www.shef.ac.uk/postgraduate/research/apply
Please clearly state the prospective main supervisor in the respective box and select Dentistry as the department.
Funding Notes
The Faculty of Medicine, Dentistry and Health has received an allocation of three EPSRC studentships for 2018 entry from the Doctoral Training Partnership grant that is awarded to the University of Sheffield to fund PhD studentships in the EPSRC remit. These studentships will be 42 months in duration, and include home fee, stipend at RCUK rates and a research training support grant (RTSG) of £4,500.
Home/EU students must have spent the 3 years immediately preceding the start of their course in the UK to receive the full funding.
References
1. Pateman CJ, Harding AJ, Glen A, Taylor CS, Christmas CR, Robinson PP, Rimmer S, Boissonade FM, Claeyssens F, Haycock JW. Nerve guides manufactured from photocurable polymers to aid peripheral nerve repair. Biomaterials 2015;49:77–89.
2. Atkins S, Loescher AR, Boissonade FM, Smith KG, Occleston N, O’Kane S, Ferguson MW, Robinson PP. Interleukin-10 reduces scarring and enhances regeneration at a site of peripheral nerve repair. J Peripher N Syst 2007;12:269–276.
3. Ngeow WC, Atkins S, Morgan CR, Metcalfe AD, Boissonade FM, Loescher AR, Robinson PP. A comparison between the effects of three potential scar-reducing agents applied at a site of sciatic nerve repair. Neuroscience 2011;181:271–277.
4. Harding AJ, Christmas CR, Ferguson MW, Loescher AR, Robinson PP, Boissonade FM. Mannose-6- phosphate facilitates early peripheral nerve regeneration in thy-1- YFP-H mice. Neuroscience 2014;279:23–32.
5. Kaewkhaw R, Scutt AM, Haycock JW. Anatomical site influences the differentiation of adipose-derived stem cells for Schwann cell phenotype and function. Glia 2011;59:734–749.
6. Kaewkhaw R, Scutt AM, Haycock JW. Integrated culture and purification of rat Schwann cells from freshly isolated adult tissue. Nat Protoc 2012;7:1996–2004.