Development of novel bioengineered conduits for peripheral nerve repair

Background: There are 300,000 peripheral nerve injuries per year in Europe (1/1,000 population) giving rise to substantial disability and, in some patients, the development of chronic pain. Repair with an autologous nerve graft is not ideal as it results in loss of function and sometimes pain from the donor site, and may be followed by a disappointing outcome. The bioengineering challenge is to create an effective conduit that will reliably promote functional outcomes that are better than those achieved by autologous nerve grafts. We have recently published a study that demonstrates the ability to manufacture a nerve guidance conduit by photolithography with micrometre resolution (microstereolithography), that is biocompatible and can support regeneration across a short gap injury over 21 days – equivalent to that achieved with an autologous nerve graft.

Hypothesis: We hypothesise that an optimally designed biodegradable microfibre nerve conduit populated with support cells will promote peripheral nerve regeneration as well as, or better than, an autologous nerve graft and would avoid graft donor site morbidity.

Aims: 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.

Objectives: The specific objectives are to establish:
1. The optimal design of the microfibre conduit.
2. Whether optimally designed conduits can perform better than autologous nerve grafts.
3. Whether our optimally designed conduits populated with anti-fibrotic agents or support cells perform better than empty conduits.

Experimental plan: We plan to use microstereolithography to construct customised porous biodegradable conduits with either a series of parallel internal microfibres or accurately aligned multi-lumen nerve guides. Comparisons will be made between nerve grafts, empty conduits and those with a range of different designs; including the addition of anti-fibrotic agents and/or cells known to facilitate nerve growth. These cells will be cultured using our established high efficiency techniques. Initially we will use genetically modified (thy-1-YFP-H) mice, which have fluorescent axons, to trace individual axons through the conduits, and determine the proportion of axons that regenerate and the length of the regenerating axons after nerve repair. We will then evaluate the most promising conduits in further detail, using a combination of methods of assessment including electrophysiological recordings of compound action potentials and functional assessment of outcome using walking track analysis.