This Lab-Grown Skin Could Revolutionize Transplants

The breakthrough sparked a debate: What do we do now? One faction wanted to grow a face, but the faction that tried to do it won. They envisioned a structure with five fingers that could be cut open at the wrist, put on like a glove, and then sewn up. “You would just have to put bandages around the wrist area – and that would be the surgery,” says Abaci.
So the lab printed a five-finger scaffold the size of a sugar packet, prepared the cells as before, and then tested how well the “edgeless” construct held up compared to traditional grafts. In the mechanical stress test, edgeless constructions beat flat spots by up to 400 percent. Microscope images revealed a healthy, more normal extracellular matrix – the network of proteins and molecules that give tissue structure. This matrix had more molecules like hyaluronic acid and a more realistic arrangement of the cells. Abaci was enthusiastic, but also surprised: “It was really fascinating to see how the cells really only react to the change in geometry. Nothing else.” He believes this method is better suited to creating a more normal skin substitute because it allows the cells to grow in a natural, cohesive manner.
But could such a skin transplant actually be take? Pappalardo’s mouse demonstration – which he ended up making 11 times – suggests so. It was not possible to perform the same operation with flat grafts; He chose the hind leg of the mouse because the geometry of the area is so complex. Four weeks later, the skin substitute was fully integrated into the surrounding mouse skin.
“The way they made this work was pretty exciting,” says Adam Feinberg, a biomedical engineer at Carnegie Mellon. “We are on the way to making these technologies more widely available. Ultimately, in about a decade, it will really change the way we repair the human body after injury or illness.”
He’s particularly excited about how they can vascularize the skin and help it grow blood vessels. This could be a great boon for people with diabetic ulcers. “Vascularization keeps the tissues alive,” Feinberg says, and one reason people get diabetic ulcers in the first place is because their tissues are poorly supplied with blood. “If [engineers] If they could create better vascular quality for the tissue first, they could have more success treating these patients,” he says.
Sashank Reddy, a plastic surgeon and tissue engineer at Johns Hopkins University, points out that the team can also grow these structures from very small biopsies, rather than having to transplant a large amount of tissue from somewhere else on the patient’s body. “Let’s say I had to resurface someone’s entire forearm — that’s a lot of skin that I have to borrow from somewhere else on their body, off their back or their thigh,” says Reddy. Removing this tissue creates an error at the “donor site” from which it was taken. “The other beauty of this approach is not only the geometry, but also that this defect is spared at the sampling point,” he continues.
And Sherman notes that a transplant that can be performed in an hour is a vast improvement over today’s transplant surgeries, which can take anywhere from 4 to 11 hours and require extensive anesthesia in a vulnerable patient. “It could be a big step forward,” says Sherman.
Video: Alberto Pappalardo/Abaci Lab
Still, the new constructs must clear several hurdles — such as clinical trials — before surgeons can use them, Reddy says. Not many companies have tried implanting artificial tissue into patients. Last year, a company called 3DBio transplanted a human ear printed from cells.
And Reddy notes that this tissue lacks several components of real skin, such as hair follicles and sweat glands. “People may consider these ‘nice to have,’ but they’re actually really important when it comes to anchoring the skin,” he says. It is important to also incorporate skin pigments to adjust skin tone. But he’s optimistic that these add-ons are viable, and he notes that surgical demos in mice are more easily extrapolated to humans than drug trials done in mice. “There are always surprises in biology, but it’s harder to say that’s going to reproduce,” he says. “It’s more of a technical problem than a fundamental discovery problem.”
Abaci sees potential in using this engineered skin to test drugs and cosmetics, as well as to study the basic biology of skin. But the main attraction for him is the production of grafts – ideally ones that can survive as a single wearable part, possibly developed with the help of other research groups specializing in muscle, cartilage or fat.
Meanwhile, his group is working on making larger constructs like an adult male hand. (They believe it would only take a 4-millimeter biopsy to harvest enough tissue to grow the 45 million fibroblasts and 18 million keratinocytes needed for a culture that size.) They also plan to use the scaffold get rid of it and start printing real tissue. Not only would that save some steps, but it would also give you more control over the thickness and functionality of the skin in different places.
Tissue engineers are confident that new approaches like this will make it to the clinic. “It’s really a question of If this will be available,” says Feinberg, “and not on If.”
https://www.wired.com/story/this-lab-grown-skin-could-revolutionize-transplants/ This Lab-Grown Skin Could Revolutionize Transplants