Miji Yeo, a postdoctoral researcher at Penn State, checks the bioink cartridges on a 3D printer developed to intraoperatively print layers of skin. (Credit: Michelle Bixby/Penn State)

Fat tissue holds the key to 3D printing layered living skin and potentially hair follicles, according to researchers who recently harnessed fat cells and supporting structures from clinically procured human tissue to precisely correct injuries in rats.

The advancement could have implications for reconstructive facial surgery and even hair growth treatments for humans. The researchers demonstrates bioprinted, full thickness skin with the potential to grow hair in rats.

While scientists have previously 3D bioprinted thin layers of skin, the researchers are the first to intraoperatively print a full, living system of multiple skin layers, including the bottom-most layer or hypodermis. Intraoperatively refers to the ability to print the tissue during surgery, meaning the approach may be used to more immediately and seamlessly repair damaged skin, the researchers said. The top layer — the epidermis that serves as visible skin — forms with support from the middle layer on its own, so it doesn’t require printing. The hypodermis, made of connective tissue and fat, provides structure and support over the skull.

The researchers started with human adipose, or fat, tissue obtained from patients undergoing surgery at Penn State Health Milton S. Hershey Medical Center. Collaborator Dino J. Ravnic, associate professor of surgery in the Division of Plastic Surgery at Penn State College of Medicine, led his lab in obtaining the fat for extraction of the extracellular matrix — the network of molecules and proteins that provides structure and stability to the tissue — to make one component of the bioink.

They achieved both the hypodermis and dermis layers, with the epidermis forming within two weeks by itself.

“We conducted three sets of studies in rats to better understand the role of the adipose matrix, and we found the co-delivery of the matrix and stem cells was crucial to hypodermal formation,” Ozbolat said. “It doesn’t work effectively with just the cells or just the matrix — it has to be at the same time.”

They also found that the hypodermis contained downgrowths, the initial stage of early hair follicle formation. According to the researchers, while fat cells do not directly contribute to the cellular structure of hair follicles, they are involved in their regulation and maintenance.