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Spray On Skin

 The drive was really around trying to understand how we could cover really bad burns which were large surface areas.

Spray-on skin cells is a fascinating story for me because it’s now coming up to 20 years of my life and I can probably encompass it in a few minutes!  The drive was really around trying to understand how we could cover really bad burns which were large surface areas.  If you've got a burn, traditionally - and we still use traditional techniques as well as the cell-based therapies here - we could take an area of your body you’re not injured on, skim a skin graft off the top, allow that area to heal, move that skin graft and put it on the wound. And you can imagine if you've got half of your body burnt, well, that’s quite challenging, because how are you going to take the other half?  And then now, all of your body is wounded.  And so we spent a lot of time over the years, not just here, of course, but globally in the burns arena, trying to expand the donor site, so whether we put it through a machine that meshes it, like a string vest, or all sorts of different strategies and different layers that we can introduce, scaffolds and layers that are coated in biologics or in various molecules.  

And so the skin cells of the dermoepidermal junction are the two main layers of skin.  You’ve got your waterproof layer and your tough layer, and the layer in between, the dermoepidermal junction, is the engine room where the skin regenerates from.  So the idea that came out of MIT in Boston in the 70s is that you can peel those two layers apart, like a bread and butter sandwich. You scrape the butter off, you put it in a favourable environment, and you can grow the cells into sheets.  That’s where we started and based on Reinhold and Green’s work growing cells in sheets, because we skin graft in sheets.  And before long, Marie Stoner and with a lab funded by Telethon in 1993, and then we realised that the skin cell sheets that did better were the ones that looked like they were a bit moth eaten because they weren't quite as mature.  We thought, this is interesting, and so we did some experiments looking at the cells, and how the surface of the cells changes with the maturity.  So when we get a cell, when we split all these cells apart, they're all dissociated, they're all apart from each other and they're looking for a mate.  And they connect, and they start to form a sheet and then once they get that sheet they then start to form layers…then those layers eventually become waterproof. That’s the normal sort of way of going.

But, interestingly, then when you take that and put it on the body, it was really hard to get it to stick and it was really fragile and really difficult to use, and took three weeks.  So we thought, hmm, this is interesting.  The cells when they're on their own are much stickier, they stick to the wound better.  And we looked at how the skin cells grew into a sheet in a box and we looked at how the skin cells on the body like in a soup healed and we thought, hmm, this is interesting.  So we started putting the cells in, like, a blister over the wound and that was messy and difficult.  Or for a hand, we’d put it in a surgical glove and allow the patient to move their hand and the cells would coat their hand, things like that.  And one day we just thought, oh, we should just spray this on.  And the two of us looked at each other like, whoa!

And so we tried all sorts of different ways of spraying, went to the art store and the chemist store, the pharmacy, the anaesthetic trolley, that’s a very good source of sprayers, throat spray, hairspray, and we found an Italian mouth freshener that had a nozzle that if we took that nozzle and put it onto a syringe - on a 5ml syringe standard - it would maintain 90% plus viability coming through with no dead space.  It was ridiculously simple and so that’s how we started spraying skin cells on.

And then, we were three weeks in the lab to grow a mature sheet.  Marie managed to grow really very good quality sheets in ten days.  We started using suspension at five days post harvesting and then…that’s still five days you’re waiting, that’s five painful days.  And so we stood back and we thought, well, could the body be the tissue culture flask?  So the surgery has to be meticulous, you have to be clean, no bleeding, no dead tissue etc. but the answer is yes.  So we then put the first steps of the whole lab process in a box and took the box to the patient and that’s what we do now, so it takes about 20 to 30 minutes.  So that’s about twenty years of my life!

But now I’m seeing all sorts of interesting utilisation going forward, it’s still in trials in the US with the armed forces using regenerative medicine, there’s colleagues in the UK using it in head and neck reconstruction, for pigment change, for acne scarring, and more recently one of my colleagues was looking at exploring the use of these cells to change radiotherapy scarring, chronic wounds and sorts of things. So when I see what everybody else has done I think, this is really good because I can learn from them and see how it’s sort of growing and moving across the world for basically skin repair, but we need skin repair in all sorts of different ways so it’s good to see the boundaries pushed.