Peripheral nerve injury: bridging the gap

Nerves are specialised cells that carry information between the brain and spinal cord, and the rest of your body, including your skin and muscles. They carry electrical signals that enable us to feel things and to move. But if we injure nerves, we can be left with permanent disabilities.  When injuries like this happen, often to people’s arms, sometimes the only way to repair a nerve and restore its function is to remove a healthy segment of nerve tissue from another part of the body - usually the leg - and use this to patch up the damage. The injured nerve then regrows using the patched-in nerve tissue to guide it back to the skin and muscles it needs to supply. Of course, this is the neurological equivalent of robbing Peter to pay Paul, because it leaves part of the leg lacking a nerve supply instead. Now Becky Shipley, from University College London, is developing a modelling system to discover how best to grow new nerve graft tissue in a dish so that patients don’t have to get a numb leg to restore functions in their arms and hands in future. Katie Haylor spoke to Becky, and also to peripheral nerve surgeon Tom Quick...

Becky - The gold standard at the moment for treating large gap peripheral nerve injuries is to graft one of these healthy sections of nerve from another part of the patient’s body, and implant it back into the gap between the severed ends of the injured nerve. Although that’s the gold standard, there’s obvious limitations to that in terms of having damage to a healthy nerve for the patient, a second surgery and beyond that, that approach actually only restores full function to the damaged nerve in about 50% of cases.

So instead, what we’re trying to do is to engineer living replacement nerve tissues in the laboratory that we can then implant into the patient instead of using their own tissues. That could be really powerful both in terms of reducing the number of surgeries for that patient but also in how successful the nerve repair actually is.

Katie - Why is it that this hasn’t been done before?

Becky - In this area there’s been a huge amount of research that’s done in labs across the UK and internationally that has explored a very broad range of different materials, so bio-materials and exciting new stem cell technologies, and tried to use them in combination to repair damaged nerves. But, in a sense, it’s almost been too successful so now we’re in the in the position where there are so many different options that it’s hard to try and optimise them using physical experiments in isolation as these experiments that we do in the labs are so expensive and time-consuming.

So what we are trying to do instead is to use a combination of all of this exciting experimental work with computational modeling, so computer-based work as part of the design process to refine how we put together these tissues in the lab.

Katie - Can you talk us through the process of ‘growing’ this nerve tissue? You’ve got cells that you’ve taken from the patient, what else is in that mixture?

Becky - In the most fundamental sense, you can think of it as a combination of cells and materials. So, like you say, we have cells which can be from the patient themselves. We combine them with what we call a ‘matrix’ which is actually a combination of different proteins. We put those together to make what we call a ‘cellular gel’ and it’s like a piece of jelly and that is, essentially, your living tissue.

What we do is we combine them in different ways, and under different physical stimuli to be able to replicate the kind of mechanical and chemical environment that these cells would experience in the body.

Katie - And it’s that that will be bridging the gap that you can’t otherwise bridge?

Becky - Exactly. That’s what we create in the lab and that’s what we would then implant into the repair site. What’s really exciting about our approach is that by introducing the computational modeling we have this whole new framework by which to streamline the design process. In the long term, we’ll be significantly reducing the costs associated with engineering a really effective and transformative nerve repair solution.

Katie - But, as peripheral nerve surgeon Tom Quick points out, there are numerous other costs to having an operation…

Tom - Theatre time is a very expensive resource and quite limited. The time to take these nerve grafts is quite considerable, but then the cost to the patient themselves having lost that function, so having lost the sensation, having extra scars. There’s an awful lot of work yet to be done on exactly the impact of having a scar on the leg when you’re having your arm repaired and how these scars affect people’s body perception and image of themselves. So cost, I think, can be looked at on a number of levels, not just financial.

Katie - So what difference could growing a patient’s nerve tissue outside the body instead of using this grafting process have for someone who’s had a traumatic nerve injury?

Tom - Certainly from my point of view as a surgeon it would give me the ability to have greater options to help patients. A number of times we look to reconstruct nerve grafts and we don’t have the ability to take enough tissue to reconstruct that as we would like.

The ability to have a product that is entirely designed for the patient, to give us everything that we want from a nerve graft from a tissue to fit a nerve gap would be amazing. The tissue that we use currently and we say is a gold standard, we’re actually using sensory nerves to reconstruct mainly motor tissue deficits and we know that that isn’t ideal. We could design it better than what we have now and actually get the right cells to do the right job from the patient themselves, so it could open up a whole new area of clinical treatments.

Katie - So is it fair to say that it might not necessarily be a difference between not being able to use your arm or being able to use your arm, but it could transform the way in which that is done and the consequences on other parts of the body?

Tom - We know from clinical research at the moment that patients’ assessment of outcome doesn’t really relate directly to individual muscle responses, how strong they are and how they recover, but it’s more a global appreciation of how their life has changed. So what we’re trying to do here is give us an awful lot more options to improve the patient experience. It may not make an arm normal; many of the injuries are actually un-reconstructable to bring it back to normal. Sort of a “humpty dumpty” injury, you can’t make it back to what it was before, but it will improve the overall experience of having a nerve injury.