Novel Bioengineered Skin Grafts

The human skin is a complex organ to bioengineer and repair because of its diverse cellular makeup, unique anatomy, and body site–specific cellular and mechanical properties. Recreating this complexity in vitro using human cells has notable implications on personalized skin replacement therapy and human-relevant skin disease modeling and drug screening.

The human skin is a continuous, fully enclosed organ, where biophysical forces between cells and the surrounding extracellular matrix (ECM) are in a mechanical balance at homeostasis. In addition, it has regional structural variations contributing to body site–specific responses during skin regeneration and wound healing

Bioengineers have developed a way to grow engineered skin in three-dimensional shapes

Bioengineers at Columbia University appear to have solved this problem by devising a way to grow engineered skin in complex, three-dimensional shapes, making it possible to construct, for example, a seamless “glove” of skin cells that can be easily slipped onto a severely burned hand.

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 crafted using computer-aided design and 3D printing. The exterior of the model is then seeded with skin fibroblasts, which generate 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 comprise most of the outer skin layer, or epidermis) and the inside is perfused with growth media, which support and nourish the developing graft.

Except for the 3D scaffold, the researchers employed the same procedures used to make flat engineered skin and the entire process took the same time, about three weeks.

In a first test of the 3D engineered skin, constructs composed of human skin cells were successfully grafted onto the hind limbs of mice. It was like putting a pair of shorts on the mice. The entire surgery took about 10 minutes.

 Four weeks later, the grafts had completely integrated with the surrounding mouse skin, and the mice reacquired full functions of the limb.

Mouse skin heals differently than human skin, so the researchers next plan to test the grafts on larger animals with skin biology that more closely matches that of humans. Clinical trials on humans are likely years away.


Alberto Pappalardo, David Alvarez Cespedes, Shuyang Fang, Abigail R. Herschman, Eun Young Jeon, Kristin M. Myers, Jeffrey W. Kysar, Hasan Erbil Abaci. Engineering edgeless human skin with enhanced biomechanical properties. Science Advances, January 31 , 2023; 9 (4) DOI: 10.1126/sciadv.ade2514