Skin grafts are a vital treatment for burns and other extensive skin injuries. Since the 1980s, advances in bioengineering have allowed researchers to grow new patches of skin in the lab. Such engineered grafts are less traumatic for patients than transplanting skin from elsewhere on the body.

To date, available techniques have only allowed such skin patches to be produced in shapes similar to bandages, such as flat rectangles or circles. These shapes work well to cover wounds on flat surfaces like the back. But using them on complex structures like the hands or face requires extensive cutting and suturing, which can cause damage and scarring.

A research team led by Dr. Hasan Erbil Abaci of Columbia University has been working on methods to make 3D engineered skin in the shape of complex body parts. Such custom grafts could then be transplanted intact, with minimal suturing required. In a new study, the team tested their skin-culture system using models of human hands and the hindlimbs of mice. Results were published on January 27, 2023, in Science Advances.

The complex process started with scanning a body part and then 3D printing a biocompatible scaffold in that shape. The scaffolds included ports to allow the infusion of different culture liquids at different stages of skin development. The scaffolds’ structure was designed to support the growth of various types of skin cells in a timed, stepwise fashion that mimics natural skin formation.

After about a month of incubating the scaffolds in sequential steps to encourage different layers of cells to grow, the researchers analyzed the engineered skin. They found that the grafts had a uniform covering of exterior skin cells, called the epidermis.

When compared with standard, flat cultured grafts, the 3D-cultured skin was more resistant to stresses produced by movement. Further analysis showed that the 3D cultures had higher levels of extracellular matrix proteins, supportive proteins found in mature skin.

A healthy blood supply is also essential to the success of grafted skin. When the researchers added cells that can grow into new blood vessels to their 3D grafts, they observed new vessel-like structures start to form. Over time, the new vessels grew toward the upper surface of the new skin.

To test the ability of their grafts to heal in a real-life scenario, the team cultured 3D grafts in the shape of the skin on mouse hindlimbs. Transplanting these ready-made grafts to injured mouse legs took less than 10 minutes. The mice regained full functioning of their legs within four weeks.

“Three-dimensional skin constructs that can be transplanted as ‘biological clothing’ would have many advantages,” Abaci says. “They would dramatically minimize the need for suturing, reduce the length of surgeries, and improve aesthetic outcomes.”

Another potential application of 3D grafts includes repairing complex structures on the face. Such 3D engineered tissues could also be used in drug development and cosmetics testing.

References: Engineering edgeless human skin with enhanced biomechanical properties. Pappalardo A, Alvarez Cespedes D, Fang S, Herschman AR, Jeon EY, Myers KM, Kysar JW, Abaci HE. Sci Adv. 2023 Jan 27;9(4):eade2514. doi: 10.1126/sciadv.ade2514. Epub 2023 Jan 27. PMID: 36706190.

Funding: NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Science Foundation.

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