Scientists and engineers from Northwestern Medicine have invented a new range of bioactive “tissue papers” that are manufactured from materials derived from organs. These papers are so flexible and thin that they can be folded into an origami bird. The new biomaterials could potentially be used to aid wound healing and to support natural hormone production in young cancer patients.

Structural proteins excreted by cells that give organs their form and structure are used to make the tissue papers. A polymer is combined with the proteins to make the material pliable.

During the research, different types of tissue paper was made from uterine, ovarian, liver, kidney, heart, or muscle proteins obtained by processing cow and pig organs. Each paper has the specific cellular properties of the organ from which it was made.

Ramille Shah, an assistant professor of surgery at the Feinberg School of Medicine and a co-author of the paper explained that this new type of biomaterials has potential in both the regenerative medicine and tissue engineering fields, as well as in drug discovery and therapeutics, as it is surgically friendly and versatile.

Shah also thinks the tissue paper could provide support and cell signaling for wound healing. These are required to help regenerate tissue to prevent scarring and will also accelerate healing.

The tissue papers are manufactured from natural tissues and organs. The cells are removed, leaving behind the natural structural proteins known as the extracellular matrix. The matrix is then dried into a powder and converted into the tissue papers. Each paper type contains residual biochemical and protein architecture from its original organ, and is able to stimulate cells to behave in a specific way.

Ovarian follicles were grown by culturing them in vitro and tissue paper was thus made from a bovine ovary. The work was carried out in reproductive scientist Teresa Woodruff’s lab. The follicles (hormone-producing cells and eggs) grown on the tissue paper produced the hormones required for proper maturation and function.

Woodruff, another coauthor of the study believes that this could provide an option to restore normal hormone function to young cancer patients. These patients often lose their hormone function due to radiation and chemotherapy. Implanting a strip of the ovarian paper with the follicles under the arm could restore hormone production for women in menopause or cancer patients.

Woodruff is the Thomas J. Watkins Memorial Professor of Obstetrics and Gynecology at Feinberg and the director of the Oncofertility Consortium.

The tissue paper made from different organs also supports the growth of adult human stem cells. When researchers placed human bone marrow stem cells on the tissue paper, all the stem cells attached and multiplied over a four week period.

Adam Jakus, first author of the paper and the developer of the tissue papers noted that the fact that that the paper supports human stem cell growth is a good sign, as this indicates that once the tissue paper is used in animal models, it will be biocompatible. He also explained that the tissue paper feels and behaves much the same as standard office paper when it is dry. Jakus stores the paper by stacking them in a freezer or a refrigerator, and has even folded them into an origami bird.

The tissue papers maintain their mechanical properties even when wet and can be folded, rolled, sutured to tissue and cut.

Jakus was a Hartwell postdoctoral fellow in Shah’s lab for the study. He then cofounded the startup company Dimension Inx, LLC with Shah. The company will primarily develop, produce and sell 3-D printable materials for medical applications. The Intellectual Property (IP) of the tissue paper is owned by Northwestern University and will be licensed to Dimension Inx.

Jakus accidentally spilt 3-D printing ink in Shah’s lab and this led to the invention of the tissue paper. Jakus was trying to make a 3-D printable ovary ink comparable to the other 3-D printable materials he had previously developed to repair and regenerate muscle, bone and nerve tissue. When he tried to clean up the spill, the ovary ink had already dried and formed a sheet.

Jakus explains that when he tried to pick it up, it felt like it was strong. He immediately realized that he could make large amounts of bioactive materials from other organs. Jakus finds it amazing that animal by-products such as a liver, kidney, uterus and heart can be converted into paper-like biomaterials that could potentially regenerate and restore function to organs and tissues.

The full study was published in the journal Advanced Functional Materials.