SAN DIEGO, March 16, 2016 -- Athletes, the elderly and others who suffer from injuries and arthritis can lose cartilage and experience a lot of pain. Researchers are now reporting, however, that they have found a way to produce cartilage tissue by 3-D bioprinting an ink containing human cells, and they have successfully tested it in an in vivo mouse model. The development could one day lead to precisely printed implants to heal damaged noses, ears and knees.

The researchers presented their work today at the 251st National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features more than 12,500 presentations on a wide range of science topics. A brand-new video on the research is available at http://bit. ly/ ACS3DPrint .

"Three-dimensional bioprinting is a disruptive technology and is expected to revolutionize tissue engineering and regenerative medicine," says Paul Gatenholm, Ph.D. "Our team's interest is in working with plastic surgeons to create cartilage to repair damage from injuries or cancer. We work with the ear and the nose, which are parts of the body that surgeons today have a hard time repairing. But hopefully, they'll one day be able to fix them with a 3-D printer and a bioink made out of a patient's own cells."

Gatenholm's team at the Wallenberg Wood Science Center in Sweden is tackling this challenge step by step. First, they had to develop an ink with living human cells that would keep its shape after printing. Previously, printed materials would collapse into an amorphous pile.

To create a new bioink, Gatenholm's team mixed polysaccharides from brown algae and tiny cellulose fibrils from wood or made by bacteria, as well as human chondrocytes, which are cells that build up cartilage. Using this mixture, the researchers were able to print living cells in a specific architecture, such as an ear shape, that maintained its form even after printing. The printed cells also produced cartilage in a laboratory dish.

"But under in vitro conditions, we have to change the nutrient-filled liquid that the material sits in every other day and add growth factors," Gatenholm says. "It's a very artificial environment."

So the next step was to move the research from a lab dish to a living system. Gatenholm's team printed tissue samples and implanted them in mice. The cells survived and produced cartilage. Then, to boost the number of cells, which is another hurdle in tissue engineering, the researchers mixed the chondrocytes with human mesenchymal stem cells from bone marrow. Previous research has indicated that stem cells spur primary cells to proliferate more than they would alone. Preliminary data from in vivo testing over 60 days show the combination does indeed encourage chondrocyte and cartilage production.

Gatenholm says further preclinical work needs to be done before moving on to human trials. To ensure the most direct route, he is working with a plastic surgeon to anticipate and address practical and regulatory issues.

In addition to cartilage printing, Gatenholm's team is working with a cosmetic company to develop 3-D bioprinted human skin. Cosmetic companies are now prohibited in Europe from testing cosmetics on animals, so they hope to use printed skin to try out makeup, anti-wrinkling techniques and strategies to prevent sun damage.

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A press conference on this topic will be held Wednesday, March 16, at 9:30 a.m. Pacific time in the San Diego Convention Center. Reporters may check-in at Room 16B (Mezzanine) in person, or watch live on YouTube http://bit. ly/ ACSliveSanDiego . To ask questions online, sign in with a Google account.

Gatenholm acknowledges funding from the Knut and Alice Wallenberg Foundation, Eurostar/Vinnova and the Västra Götalands Regionen.

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Title

3D Bioprinting of Living Tissues and Organs with Polysaccharide Based Bioinks and Human Cells

Abstract

The introduction of 3D bioprinting is expected to revolutionize the field of tissue engineering and regenerative medicine, which enables the reconstruction of living tissue and organs using the patient's own cells. The 3D bioprinter is a robotic arm able to move in the X,Y,Z directions with a resolution of 10μm while dispensing a bioink and positioning several cell types and thus can reconstruct the architecture of complex organs. There are rigorous requirements for material to be able to be used as a bioink for 3D bioprinting with human cells and natural and synthetic hydrogels are currently being evaluated for these applications. We have discovered that cellulose nanofibrillar dispersion has unique shear thinning properties which is perfect for providing high fidelity during bioprinting. We have developed a new bioink, CELLINK, for printing living soft tissue with cells. CELLINK is composed of a nanofibrillated cellulose dispersion and alginate which is crosslinked during printing. The human chondrocytes have been successfully printed with CELLINK in complex 3D shape of human ear and cells showed good viability after printing and crosslinking. Long term study showed cartilage formation in 3D Bioprinted constructs. We have evaluated this new bioink with mesenchymal stem cells and human dermal fibroblast for providing human skin models for testing cosmetics and for cancer research. Recently several projects started in collaboration with plastic surgeons with aim to translate our finding into clinical applications.