Application deadline: 3rd March
Interviews to be held: 31 March 2021
Promoting nerve regeneration following trauma is a major surgical challenge. There is an estimated incidence of 1 million peripheral nerve injuries annually world-wide, with huge socio-economic cost. Current standard practice for nerve gap repair is autologous nerve autografting despite deficiencies such as limited availability and harvesting of functioning nerve, donor site morbidity, time‐consuming surgeries, or incomplete recovery. There are commercially available nerve guidance conduits, however none of these are better than the gold standard and there is unmet clinical need for improved scaffolds with guidance cues. Biomaterials are being developed to manipulate cellular interactions with their environment. The majority of engineered systems present signals (mechanics, topography, adhesion) in a spatially uniform manner. Biochemical patterns are more indicative of natural extra cellular matrix (ECM) signalling that occurs through gradients and spatial localisation of biomolecules, and their use in combination with topographical features is a powerful tool for guiding axons to their synaptic targets.
This project seeks to develop advanced silk-based nerve guidance conduits (NGCs) using additive manufacture and photo-click technology to provide stimulatory cues to guide neuronal cells to their synaptic targets. We will combine 3D additive scaffold manufacture (foams and nanofibre hierarchical structures) which provide morphological cell guidance cues, with advanced photo-click technology to tether growth factors/adhesion molecules and electrically conductive elements in defined patterns and gradients, with target resolutions that are relevant to cells (approaching 100 nm). The combination will allow a new generation of stimulatory hierarchical NGCs to be produced with tethered growth factors patterned in the interior of the 3D conduit, as a tool to optimise axonal growth.
Main questions to be answered
With the overarching aim of directing axonal growth and Schwann cell adherence in 3D macroporous/fibrillar scaffolds as improved nerve guidance conduits:
1) What resolutions can be photo-clicked onto fibres (of diameter ~1 micron), aligned fibre mats and macroporous foams of functionalised silk* using 2-photon lithography and what are the speed limitations?
2) Can photo-clicked patterns be obtained in 3D structures using holographic projection lithography, and what resolutions are achievable?
3) Can recombinant reflectin* (one of the highest proton conductors in nature) be clicked to generate electrically stimulatory patterns on silk?
4) Which tethered growth factors (e.g. laminin, laminin-1, NGF, CNF, RGDS) and reflectin, concentrations, shapes distributions, or combinations have positive effect on axonal growth and cell motility?
*Recombinant silk containing lysine groups, and recombinant reflectin will be supplied by collaborators in the Manchester Institute of Biotechnology
EPSRC Centre for Doctoral Training in Advanced Biomedical Materials
This project is part of the EPSRC Centre for Doctoral Training in Advanced Biomedical Materials. All available projects are listed here.
Find out how to apply, with full details on eligibility and funding here.
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