Peripheral nerve reconstruction: NO hope for advanced regeneration

Traumatic peripheral nerve injury (PNI) is common and mainly affects the upper limbs of young economically active adults, of both genders. PNI presents serious economic consequences for the patient, and society as a whole, and despite modern microsurgical techniques, functional restoration is always incomplete. For the patient, the outcome is impaired hand sensation, reduced motor function alongside pain and cold intolerance; furthermore, the enduring nature of these symptoms frequently results in psychosocial morbidity and a lifelong impairment of well-being.
The greatest reconstructive challenge lies with the approximately 1 in 5 PNI patients with a 'nerve gap' (i.e. a nerve defect caused by the trauma) where direct repair of the two nerve stumps is not possible. Nerve gaps may be reconstructed using autologous nerve grafts, which sacrifice sensory function in parts of the lower limb in an effort to restore critical function in the hand. The outcomes following nerve grafting are poor and worsen with increasing gap distance.
We have developed a polymer nerve repair device 'Polynerve' that has a simple easily upscalable manufacturing methodology; by incorporating grooves on the inner lumen of the conduit, it attempts to address the biology of the Schwann cell - guiding regeneration following PNI. We have completed Phase 1 clinical trials in Manchester with excellent outcomes on small nerve gap injuries.
Now, we seek to augment the biological response at the site of injury to favour regeneration. Nitric Oxide (NO) is a potent free radical that regulates multiple biological processes with involvement in neuronal and vascular regeneration likely via macrophage interaction. It is known that macrophage-induced new blood vessel formation leads Schwann cell-mediated regeneration of peripheral nerves; thus, NO is a potential intervention to augment PNI regeneration.

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.