Title: Translating a novel synthetic polymer nerve conduit to human scale
Funder: Department of Health and Social Care

Abstract: This research builds on previous successful studies of a novel nerve conduit supported by an NIHR i4i grant and aims to produce a medical device for application in the NHS. We will engineer the inner lumen of the conduits with optimised physical cues for human nerve repair. The product will be the conduit possessing the nano and micro-features. This product prototype will be tested using biomechanical, physical and cell culture techniques. Alongside these pre-clinical experiments will be the consideration of regulatory approval, manufacturing, sterilisation, packaging etc. We will also need to find an Industrial partner for the commercialisation of the product. We aim to produce an off-the-shelf product for clinical use as a peripheral nerve conduit. Making the prototype product: Micro grooved polymer films will be fabricated by solvent casting. Patterned microgroove silicon substrates will be used as a template for casting polymer solution. The grooved specification will be optimised to improve cells elongation. Patterned silicon substrates will be prepared by photolithography and wet/dry etching. The patterned shape and width-space-depth will be optimised for maximal adhesion and elongation of human adipose stem cells. Surface and cell interface characterisation will be carried out by scanning electron microscopy (SEM), atomic force microscopy (AFM), and the synchrotron at the Diamond Light Source facility, Oxfordshire. The wettability properties of the polymer can be modified and the surface hydrophilicity will be determined by measuring contact angle. In vitro studies of human neuronal cell lines regenerating axons across the surface will be used to determine further the optimum microgroove physical characteristics. The morphology of hASC differentiated to Schwann cells will be examined with scanning electron microscopy (SEM) and immunocytochemistry. Testing the prototype product with human cell cultures: Human ASC will be isolated from donated fat specimens and differentiated to a Schwann cell lineage using in vitro cell-culture techniques that we have previously developed on animal models. The differentiation process will be monitored at several stages by measuring the gene and protein expression (qRT-PCR, Western Blotting) and secretion of growth factors such as NGF, BDNF, and GDNF (ELISA tests), which are known to be expressed by Schwann cells but not by ASC. These in vitro experiments are planned to mimic the action of Schwann cells at the site of nerve regeneration that occurs in vivo to optimise the method of generating clinically significant and functional cells to incorporate in polymer nerve conduit repair.

Lay abstract: Peripheral nerve injuries are a common occurrence, with approximately 9000 cases in the UK occurring each year, in a predominantly young and working population. Despite advances in microsurgical nerve repair techniques, functional recovery is often poor which can have a profound and permanent impact on the patient recovery and quality of life. Nerve repair has significant health, social and cost implications with the treatment and rehabilitation of an employed person, estimated to be EUR 51,238 (&pound;44,500). The current method to repair a nerve gap is to graft a nerve taken from another area of the patient. This results in morbidity and second surgical procedure and there is limited donor nerve availability. This has prompted research on the use of bio-engineered nerve conduits, an artificial means of guiding axonal regeneration. However, all commercially available conduits to date have not been able to match the results of the current clinical technique, of reconstruction using nerve graft. This research proposal attempts to develop a solution for faster and improved quality of peripheral nerve repair using a specialised biodegradable nerve conduit. The conduit will be tested using cells derived from human adipose stem cells. Specifically, the novel conduit will be developed for human applications. The use of a bio-engineered conduit has the potential to transform outcomes of peripheral nerve injury. This research proposal will produce significant experimental data which will position the researchers to exploit the IP and generate an effective technology for translation into clinical practice.

Research activity codes: 5.3 MEDICAL DEVICES
Health categories: NEUROLOGICAL