3D-printed skin closes wounds and contains precursors of hair follicles

Adipose tissue is the key to 3D printing layered living skin and possibly hair follicles. This is reported by researchers at Penn State University who recently harnessed fat cells and supporting structures from clinically procured human tissue to precisely correct injuries in rats. This advance could have implications for facial reconstructive surgery and even the treatment of hair growth in humans.

The team used clinically procured human adipose tissue and supporting structures to precisely correct injuries in rats. They focused on creating a full thickness of skin, including the lowest layer, the hypodermis. This layer, consisting of connective tissue and fat, forms the structure and support over the skull and is directly involved in the process by which stem cells become fat. This process is critical to several vital processes, including wound healing and the regulation of the hair follicle cycle.

Dr. Ozbolat and his team are the first to bioprint a complete, living system of multiple skin layers intraoperatively.

“Reconstructive surgery to correct trauma to the face or head from injury or disease is usually imperfect, resulting in scarring or permanent hair loss,” said Ibrahim T. Ozbolat, professor of engineering science and mechanics, of biomedical engineering and of neurosurgery at Penn State, who led the international collaboration that conducted the work. “With this work, we demonstrate bioprinted, full thickness skin with the potential to grow hair in rats. That’s a step closer to being able to achieve more natural-looking and aesthetically pleasing head and face reconstruction in humans.”

The researchers began with human adipose tissue procured from patients at Penn State Health Milton S. Hershey Medical Center. Dino J. Ravnic, Associate Professor of Surgery at Penn State College of Medicine, and his team extracted the extracellular matrix from the adipose tissue to create one component of the bio-ink. Another component was derived from the stem cells of the adipose tissue. These components were loaded into a three-chamber bioprinter, with the third chamber containing a clotting solution that helped to properly bind the other components to the injured site.

The study showed not only the formation of the hypodermis and dermis, but also the formation of downgrowths, the initial phase of hair follicle formation, within two weeks.

“The hypodermis is directly involved in the process by which stem cells become fat,” Ozbolat said. “This process is critical to several vital processes, including wound-healing. It also has a role in hair follicle cycling, specifically in facilitating hair growth.”

“The three compartments allow us to co-print the matrix-fibrinogen mixture along with the stem cells with precise control,” Ozbolat said. “We printed directly into the injury site with the target of forming the hypodermis, which helps with wound healing, hair follicle generation, temperature regulation and more.”

“In our experiments, the fat cells may have altered the extracellular matrix to be more supportive for downgrowth formation,” Ozbolat said. “We are working to advance this, to mature the hair follicles with controlled density, directionality and growth.”

This research offers a hopeful path forward, especially when combined with other projects from Dr. Ozbolat’s lab looking at printing bone and studying how to match pigmentation across different skin tones.

“We believe this could be applied in dermatology, hair transplants, and plastic and reconstructive surgeries — it could result in a far more aesthetic outcome,” Ozbolat said. “With the fully automated bioprinting ability and compatible materials at the clinical grade, this technology may have a significant impact on the clinical translation of precisely reconstructed skin.”