Skin substitute to repair burns

20 August 2019

Interview with 

Malavika Nair & Tricia Smith, University of Cambridge

HOSPITAL

Hospital scene

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Skin is one of our most important - and largest - organs. It keeps out unwanted invaders, regulates our temperature and prevents us from dehydrating, or swelling up in the rain! But, it is very much in the firing line, sometimes literally, meaning it can succumb to severe burns. And these may require healthy skin to be transferred or grafted from another body area to repair the damage. But, when the burn covers a very large area, obtaining sufficient skin for such a graft can be difficult. Now researchers at the University of Cambridge have developed a technique to create repair materials made from collagen, the connective material that gives skin its strength. Tricia Smith and Malavika Nair brought some into the studio to show Izzie Clarke.

Malavika - What I've given you there is a collagen scaffold, and it's basically 99% air and 1% collagen. It's a scaffold material, which is basically what we're used to seeing in terms of building; so they're just temporary structures that we put up so that the people who are doing the construction work can weave through, and lay down the foundation to the building, and repair it. And in a similar way within the body what we want is the cells to recognise these scaffold areas, weave through them, and lay down new tissue and regenerate this tissue.

Izzie - So how do you make one of these things?

Malavika - To make a collagen scaffold we go through a process known as freeze-drying. So what we're freeze-drying here is essentially a suspension of collagen and acetic acid, so that’s just vinegar and collagen put together and blended up. When we then put this into the freezer, we allow ice crystals to grow. Now ice is quite particular because it actually doesn't like a lot of foreign bodies within its crystal structures. So collagen is a foreign body; as the ice crystals grow, the collagen would be excluded off to the side of the ice, but it allows then the collagen to pack around the ice and be templated by these ice crystals.

Izzie - I see. And so how do you get rid of the ice?

Malavika - To get rid of the ice we go through this process known as sublimation. Now sublimation is a process where we go from the solid to the vapour and just skip the liquid phase entirely. If we were to drop the temperature back up to room temperature then we'll just melt it, and it will just get rid of all this beautiful structure that we've created and we're trying to keep. We reduce the pressure in this freeze-dryer and we allow these ice crystals to then go to vapour, and then we are left just with the empty space with the collagen packing around this empty space. These empty spaces basically serve as the channels for the cells to move through when we put cells onto these scaffolds or when we put the scaffold into the body.

Izzie - This one that you've given me is quite spongy. Because we’ve got so much different tissues in our body, can you change the properties of it?

Malavika - Absolutely. So collagen is quite ubiquitous in our body and we find it in tissues that are very different mechanically and biologically. So we find collagen in the skin, in the heart, in the cornea, and even bone; so we can tell that we don't really want the same collagen that we have in our bone in our skin, or vice versa. So in the same way, what we do is we can tailor both the chemistry and the mechanics of this collagen scaffold through various processes, one of which is cross-linking. So cross-linking allows you to improve the mechanical properties and to stiffen it. So that would prevent us from putting something that's more suited for the skin into the bone, for example.

Izzie - And Tricia, how does this collagen scaffold help skin - or burnt skin - to heal?

Tricia - So what it actually does is instead of allowing the burnt area to heal, it interrupts the healing process; because when normal skin heals, when you have a big area that's damaged, what happens is the skin will contract so that you have as small an area as possible, and then a scar will form. And that scar doesn't have the same mechanical properties, it doesn't have the same structure as healthy skin, and therefore it doesn't perform the same function. And if you have a large area that's damaged actually what can happen is you lose mobility of that area, you lose temperature control, you lose all of these things you listed at the beginning. So what the scaffold does is it blocks the contraction of that wound and that promotes something called regeneration rather than scar formation.

Izzie - If I had a particularly nasty burn, this would get introduced to that damaged area, then what happens? Does it just stay in the body?

Tricia - So what happens is that cells will be recruited into the scaffold and will start to lay down their own healthy tissue and their own collagen, and at the same time break down that scaffold so that in three weeks’ time, four weeks’ time, it will be gone. And all you'll have left is regenerated tissue which functions correctly, and none of the original scaffold.

Izzie - So how well does it work? What results have we seen?

Malavika - So one of the examples of successful collagen implants being put in is in cartilage repair. And cartilage repair, this can pertain to the meniscus - so this is in the knee - or even just anywhere where there's a join between lubricating joints and the bone. So one example of this is where they've tried to have a bridge between the bone, which is filled with minerals and a lot stiffer, as opposed to the cartilage which is a lot more spongy and it's a lot more fluid in some ways because we want to try and lubricate that joint. And this has made it out into a commercial application.

Izzie - So it's really important that actually it's not just these burns that we're talking about. This could repair a lot of areas of the body. Could this do internal organs should one of those get damaged or need help in the future?

Malavika - Absolutely. Anything that is based on collagen, which is pretty much every organ in the body, could be serviced by collagen scaffolds as long as we put the right chemistry in it. If we can tailor all of these properties, including the mechanics degradation, then we might be able to tailor it just for pretty much any organ in the body.

Izzie - And Tricia, what are you currently doing to improve how these scaffolds can help that natural healing process?

Tricia - So we already know that the scaffold itself - when it has the right degradation properties, the right mechanical properties, the right pore size - can stop contraction and promote regeneration of the skin. But one of the ways in which these skin grafts fail is that they're not nourished correctly in the centre, and that is because there's a failure for blood vessels to grow in from the edge of the wound into the center of the graft and provide the oxygen needed for the cells to proliferate there. So what we're trying to do at the moment is retain some structure which promotes that regeneration, so the right pore size for that sort of thing, but also add in regions to the scaffold where we can promote that ingrowth of blood vessels from the edges of the wound to the center.

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