by If you’ve ever tried gift-wrapping an oddly shaped gift like a teddy bear, you’ll appreciate the challenge surgeons face when transplanting artificial skin onto an injured body part. Like wrapping paper, engineered skin comes in flat pieces that can be difficult and time-consuming to sew together around an irregularly shaped body part.
Bioengineers at Columbia University seem to have solved this problem by finding a way to grow artificial skin into complex, three-dimensional shapes, making it possible to construct, for example, a seamless “glove” from skin cells that can be easily slipped on severely burned hand.
The researchers reported their findings in an article published Jan. 27 scientific advances.
“Three-dimensional skin constructs that can be transplanted as ‘biological clothing’ would have many advantages,” says lead developer Hasan Erbil Abaci, PhD, assistant professor of dermatology at Columbia University’s Vagelos College of Physicians and Surgeons. “They would drastically minimize the need for suturing, shorten the duration of surgeries, and improve esthetic outcomes.”
The current study also found that the 3D continuous grafts have better mechanical and functional properties than traditional composite grafts.
3D framework
The process of creating the new skin grafts begins with a 3D laser scan of the target structure, such as a human hand. Next, a hollow, permeable model of the hand is made using computer-aided design and 3D printing. The exterior of the model is then seeded with dermal fibroblasts, which form the skin’s connective tissue, and collagen (a structural protein). Finally, the outside of the mold is coated with a mixture of keratinocytes (cells that make up most of the outer layer of skin, or epidermis) and the inside is infused with growth media that will support and nourish the developing graft.
With the exception of the 3D scaffold, the researchers used the same processes used to create flat-engineered skin, and the entire process took the same amount of time, around three weeks.
In a first test of the 3D engineered skin, constructs made from human skin cells were successfully transplanted onto the hind legs of mice. “It was like putting shorts on the mice,” says Abaci. “The entire operation took about 10 minutes.” Four weeks later, the grafts had fully integrated into the surrounding mouse skin, and the mice regained full limb functions.
Mouse skin heals differently than human skin, so the researchers plan to next test the grafts on larger animals with skin biology more closely matched to humans. Human clinical trials are likely years away.
Redesign of engineered skin
The 3D grafts are the first major redesign of artificial skin grafts since their introduction in the early 1980’s. “Engineered skin started out with just two cell types, but human skin has about 50 cell types. Most of the research has focused on mimicking the cellular components of human skin,” says Abaci. “As a bioengineer, it has always bothered me that the geometry of the skin has been overlooked and grafts have been made with open borders or edges. We know from bioengineering other organs that geometry is an important factor affecting function.”
Abaci and his team realized they could make more lifelike grafts when 3D printers became available and create three-dimensional scaffolds needed to create the artificial skin.
“We hypothesized that a fully enclosed 3D shape would more closely mimic our natural skin and be mechanically stronger, and that’s exactly what we found,” says Abaci. “Simply staying true to the continuous geometry of human skin greatly improves the composition, structure and strength of the graft.”
In the future, Abaci envisages that transplants could be custom-made from the patient’s own cells. With just a 4 x 4mm sample of skin, enough cells can be cultured and propagated to produce enough skin to cover a human hand.
“Another compelling application would be in face transplants, where our wearable skin integrates with underlying tissues such as cartilage, muscle and bone, offering patients a personalized alternative to cadaveric transplants,” says Abaci.
The research was funded by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (5K01AR072131) and the epiCURE Center at Columbia University Irving Medical Center (5P30AR069632).
dr Abaci has a pending patent application for this technology.
