The breakthrough sparked controversy: What are we doing now? One faction wanted to grow a face, but the faction that wanted to try their hand won. They introduced a five-finger structure that could be cut at the wrist, worn like a glove, and then sewn up. “You will only need to put bandages on the area of the wrist – and this will be an operation,” Abachi says.
So the lab printed a five-fingered scaffold the size of a sugar bag, prepared the cells the same way as before, and then tested how well the “endless” design held up compared to traditional grafts. In the mechanical load test, designs without edges outperform flat sections by 400 percent. Microscopic images showed a healthy, more normal extracellular matrix, a network of proteins and molecules that provide tissue structure. This matrix had more molecules, such as hyaluronic acid, and a more realistic arrangement of cells. Abaci was delighted, but at the same time surprised: “It was very exciting to see how the cells really only respond to a change in geometry. Nothing else.” He thinks this method is better for creating a more normal skin substitute because it allows the cells to grow in a natural, closed fashion.
But can such a skin graft really take? Pappalardo’s demonstration of the mouse, which he ended up doing 11 times, testifies to this. It was not possible to perform the same operation with flat grafts; he decided to try the hind limb of a mouse because the geometry of the area is very complex. Four weeks later, the skin replacement was fully integrated into the surrounding skin of the mouse.
“The way they made it work was pretty exciting,” says Adam Feinberg, a biomedical engineer at Carnegie Mellon. “We are on our way to making these technologies more widely available. Ultimately, in about ten years, this will really change how we can repair the human body after injury or illness.”
He’s especially excited about how they can vascularize the skin, helping it grow blood vessels. This can be a huge boon for people with diabetic ulcers. “Vascularization is what keeps the tissue alive,” Feinberg says, and one of the reasons people get diabetic ulcers in the first place is because their tissues don’t have enough blood flow. “If [engineers] If they could improve the vascular tissue quality to begin with, they could be more successful in treating these patients,” he says.
Sashank Reddy, a plastic surgeon and tissue engineer at Johns Hopkins University, notes that the team could also grow these structures from very small biopsies, instead of grafting large amounts of tissue from elsewhere on the patient’s body. “Let’s say I had to refinish someone’s forearm — that’s a lot of skin that I have to borrow somewhere else from their body, from their back or hip,” says Reddy. Removal of this tissue creates a defect in the “donor site” where it was taken from. “Another beauty of this approach is not only in the geometry, but also in the fact that it eliminates the defect in the donor site,” he continues.
And Sherman points out that transplants, which can be done in an hour, are a huge improvement over today’s transplant surgeries, which can take anywhere from 4 to 11 hours and require extensive anesthesia for a vulnerable patient. “This could be a big step forward,” Sherman says.
However, new designs will have to overcome several hurdles, such as clinical trials, before surgeons can use them, Reddy says. Few companies have attempted to implant artificial tissues in patients. One called last year 3DBio transplanted into a human ear printed out of cells.
And Reddy notes that this tissue lacks some of the components of real skin, such as hair follicles and sweat glands. “People may think of them as ‘nice things’, but they’re actually very important for firming the skin,” he says. It is also very important to use skin pigments to match the skin tone. But he is optimistic that these additions are achievable and notes that surgical demonstrations in mice are more easily transferred to humans than drug trials conducted in mice. “There are always surprises in biology, but it’s easier to say that it will reproduce,” he says. “It’s more of an engineering problem than a fundamental discovery problem.”
Abaci sees potential in using artificial skin to test drugs and cosmetics, as well as to study the fundamental biology of the skin. But his focus is on creating grafts—ideally ones that can be worn as a whole and that could be developed with the help of other muscle, cartilage, or fat research groups.
In the meantime, his group worked on larger designs, such as a grown man’s arm. (They think it only takes a 4mm biopsy to get enough tissue to grow the 45 million fibroblasts and 18 million keratinocytes needed for a culture of this size.) They also plan to do away with the scaffold and start printing real tissue. Not only would this remove some of the steps, but it would also give them more control over the thickness and functionality of the skin in different places.
Tissue engineers are confident new approaches like this will make their way into the clinic. “It really becomes a question When whether it will be available, Feinberg says, rather than If.”