Swiss scientists have developed a breakthrough technique that could see full-thickness skin grown in the lab, complete with blood and lymph vessels.
Skin grafting has been used to treat major burns and wounds for some 30 years. It is also used in a range of procedures including plastic surgery. But scientists have only been able to grow top layer skin and have been using a “sandwich technique” that involves using dead donor skin to cover the wound while a fresh layer is grown in the lab.
But using specialist human endothelial cells (which line blood and lymphatic vessels) combined with fibroblast cells, which help to build tissue, the scientists were able to create human bio-engineered skin with functioning lymphatic vessels in a 3D gel in three weeks. Lymphatic vessels are important in regulating tissue fluid and carrying immune cells – vital if grafted skin is to settle in properly.
The scientists, who published in Science Translational Medicine, showed that these vessels branched and took up fluid 14 days after being transplanted onto rodents whose immune systems had been knocked out.
The current way of skin grafting involves a “sandwich technique” which involves first taking a sample of cells from a patient or scraps of skin. These are then expanded to grow more skin in just a few weeks. When major burns are treated, the burned skin of a patient is removed leaving a wound base of fat or tissue that can be covered with skin from a dead donor. This allows the body to grow new vessels into the lower part of the skin (the dermis) and creates a barrier layer that leaves enough time for the patient’s own skin to be grown in the lab.
When it is ready, a surgeon will then remove the top layer of the donor skin and attach the lab skin. In the US, a commercial product called Integra, an artifical skin made of silicone and collagen, is used rather than donated skin.
But there are drawbacks to doing skin grafts this way. Sheila MacNeil, a professor of tissue engineering at Sheffield University, said: “Conventional skin grafting takes skin from one part of the body and grows it to be big enough to cover the affected area. Everyone has been able to make skin that looks good but when you put it on the wound bed the big problem is getting it vascularised and blood pumped into it fast enough. Problems begin because it’s not just about creating barrier skin but also the dermis.”
Essentially, you can’t just lay a piece of skin onto a wound because without an adequate blood supply it will die. And some people, like the elderly, aren’t able to grow new vessels so easily even with donor skin.
Moving things on
While it has been suspected that growing full-thickness skin involved more than just one set of cells, it is the first time scientists have shown a way to do it with two.
Sheila MacNeil, professor of tissue engineering at Sheffield University, said the sandwich technique of skin grafting was where medicine had been “stuck for some time”.
“You can’t just bung endothelial cells into skin and hope they work,” she said. “Endothelial cells are specialist, they only do one thing. They can line the tubes but they’re not up to the whole job. You need a combination of two cells.”
“Here they’ve used fibroblasts working as ‘helper cells’ to make the tubes. They’ve shown that they can make it work in 3D with tubes that look like early stage blood vessels and lymph nodes. It’s a very clever paper.”
She said the next step would be to show it could work in rodents that were not immunosupressed – in other words in rodents that have working immune systems to test how much transplanted skin might be rejected. But while the work ahead would be painstaking, it could reach early clinical applications with two to three years work, rather than ten years.
Ash Mosahebi, a consultant surgeon and lecturer in cosmetic surgery at UCL, said having blood vessels in bio-engineered skin would speed up integration of the skin following transplant surgery and could improve the final outcome.
“This is part of the general trends and advances in regenerative and reconstructive surgery,” Mosahebi said. “As we are developing and using more bio-active products and substitutes to improve the outcome of the treatments … The eventual aim would be to tailor-make grafts and replacements for a particular patient from their own cells.”
The drawbacks included cost and bio-engineered skin “not having biological constituents such as hair and sweat glands.” They can also be difficult to use and prone to infection, he said.