The breakthrough sparked a debate: What are we making now? One faction wanted to grow a face, but the faction that wanted to try a hand won. They envisioned a five-finger structure that could be cut open at the wrist, put on like a glove, and then stitched up. “You would only need to bandage around the wrist — and that would be the surgery,” says Abaci.
So the lab printed a five-finger scaffold the size of a sugar packet, prepped the cells as before, and then tested how well the “rimless” construction held up compared to traditional grafts. In a mechanical load test, rimless structures beat flat pieces by up to 400 percent. Microscope images revealed a healthy, more normal extracellular matrix – the network of proteins and molecules that give structure to tissue. This matrix had more molecules, such as hyaluronic acid, and a more realistic layout of cells. Abaci was delighted, but also surprised: “It was really fascinating to see how the cells really react to just the change in geometry. Nothing else.” He thinks this method is better at creating a more normal skin substitute because it allows cells to grow in a natural, closed way.
But is such a skin graft actually possible? to take? Pappalardo’s mouse demonstration – which he ended up doing 11 times – suggests so. It was not possible to perform the same operation with flat grafts; he chose to try the mouse hind leg because the area’s geometry is so complex. Four weeks later, the skin replacement was fully integrated into the surrounding skin of the mouse.
“The way they got this to work was pretty exciting,” said Adam Feinberg, a biomedical engineer at Carnegie Mellon. “We are on track to make these technologies more widely available. Ultimately, in about ten years’ time, it will really change the way we can recover the human body after an injury or illness.”
He’s particularly excited about how they can vascularize the skin, which allows blood vessels to grow. That could be a huge boon for people with diabetic ulcers. “Vascularization is what keeps tissue alive,” says Feinberg, and one of the reasons people get diabetic ulcers in the first place is because their tissue gets poor circulation. “If [engineers] could provide better vascular tissue quality to begin with, they could be more successful in treating those patients, he says.
Sashank Reddy, a plastic surgeon and tissue engineer at Johns Hopkins University, points out that the team could also grow these structures from very small biopsies, rather than having to transplant a large amount of tissue from elsewhere on the patient’s body. “Say I had to resurface someone’s entire forearm — that’s a lot of skin I have to borrow from somewhere else on their body, on their back, or their thigh,” says Reddy. Removing that tissue creates an error on the “donor site” it was taken from. “The other beauty of this approach is not just the geometry, but that the donor site defect is spared,” he continues.
And Sherman notes that a transplant that can be done in under an hour is a huge improvement over current graft surgeries, which can take between 4 and 11 hours and require extensive anesthesia for a fragile patient. “It could be a big step forward,” says Sherman.
Video: Alberto Pappalardo/Abaci Lab
Still, the new constructs will have to pass several hurdles, such as clinical trials, before surgeons can use it, Reddy says. Not many companies have attempted to implant engineered tissue into patients. One called last year 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 might think of these as ‘nice to haves,’ but they’re really, really critical when it comes to anchoring the skin,” he says. It is crucial to also include skin pigments, matching the skin color. But he’s optimistic that these add-ons are feasible, noting that surgical demos in mice translate more easily to humans than drug trials done on mice. “There are always surprises in biology, but it’s less of a leap to say this will propagate,” he says. “It’s more of a technical problem than a fundamental discovery problem.”
Abaci sees opportunities to use this engineered skin to test drugs and cosmetics, and to study the fundamental biology of the skin. But the biggest draw for him is creating transplants – ideally ones that can pass as a single wearable piece and perhaps be developed with the help of other research groups specializing in muscle, cartilage or fat.
Meanwhile, his group has been working on making larger constructions, such as a grown man’s hand. (They think it only takes a 4-millimeter biopsy to get enough tissue to grow the 45 million fibroblasts and 18 million keratinocytes needed for a culture of that size.) They also plan to take the scaffold down. and start printing real fabric. That would not only remove some steps, but would also give them 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 really becomes a matter of when will this be available,” says Feinberg, “and not one if.”
