Bioactive nerve guides - anti-inflammatory and anti-scarring devices

Injury to peripheral nerves through trauma, and sometimes surgery, results in over 300,000 cases each year in the EU. In contrast to the central nervous system, proximal motor and sensory axons 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, as end-end anastomosis. A fundamental understanding of the molecular and cellular responses to injury is essential when designing approaches for repair, especially for implantable nerve guide conduits (NGCs). We have reviewed NGC performance in detail1, with conclusions supporting biomaterials improvements in NGCs a realistic approach (e.g. versus cell therapy). NGCs are typically made from inert biomaterials (e.g. polyesters, collagen), and do not stimulate neuronal or Schwann cell adhesion, migration or differentiation for nerve repair. Consequently, existing devices are poor at supporting regeneration. A major challenge is to increase regeneration distance from a few millimetres to critical gap distances of 10-20 mm. For clinically practical improvement, simple innovations in the biomaterial chemistry, in combination with fabrication methods for making porous and flexible materials to reflect the mechanical properties of nerve are proposed and will be investigated in this project. In this project we also will address the problems of inflammation and scarring associated with nerve repair. Devices will therefore delivery key anti-inflammatories (a-MSH, IL-10) and/or an anti-scarring compound (M6P) known to improve functional repair. Devices will be evaluated in vitro, and in vivo in this PhD project, with a route to following on a clinical study of lingual nerve reconstruction.

There are numerous beneficiaries of this Advanced Biomedical Materials CDT. Firstly and of short term impact are the PhD students themselves. They will receive extensive research specific and professional/transferable skills training throughout the 4 years of the programme. They will have access to state of the art facilties and world leading academics, industry and clinicians. The training and potential placements are designed to maximise the impact of their research in terms of dissemination and movement of their research along the translation pathway.

Longer term benefits are that this distinct cohort will become the future UK Biomedical Materials leaders and be able to use their bespoke training and network within the cohort to collaborate on future worldwide funding opportunities and drive UK research in this area.

UK and international academics will benefit as they will gain the next generation of highly skilled postdoctoral researchers with knowledge and expertise not only in their specific research area but of industry, regulatory and clinical aspects.

UK and international industry will benefit - in the short term they will gain academic based research to further develop products and in the longer term have a pool of highly skilled graduates.

Clinicians will benefit from collaborative research and also the development of new and novel products to enhance the treatment of a variety of trauma and disease based needs from biomaterials.

The public will benefit as end users as patients that will have their quality of life improved from the products developed in the CDT and will be educated in novel technologies and materials to repair the human body. The UK economy will benefit from the reduced healthcare costs associated with the new and improved medical products developed in this CDT and subsequently from the trained graduates. The UK economy will also benefit from the increased revenue from medical sales products from the UK industrial partners we will be working with.

The impact of this CDT will be realised by direct academic, clinical and industrial engagement with the students allowing efficient and state of the at training and fast translation of developing products. Students will also be trained in knowledge exchange and will use these skills to disseminate their research to, and liaise with, the key stakeholders - the academic, industrial, clinical and public sectors. We will ensure widening participation routes are addressed in this CDT in order to include equality and diversity not only in our initial CDT student cohort but in future researcher generations to come.