3D Printing Accident Leads to ‘Tissue Paper’ with Healing Properties

One of the biggest stories in medical 3D printing from the past few months came out of Northwestern University, where researchers 3D printed a working ovary and implanted it into a mouse, which then successfully became pregnant and gave birth. That was an incredible achievement in itself, and represents a beacon of hope for women suffering from infertility. While the team was developing the 3D printed ovary, however, the study also branched out in another direction, thanks to a fortuitous accident.

While Adam Jakus, a postdoctoral fellow in Professor Ramille Shah’s lab, was preparing 3D printing ink made from ovarian cells, he accidentally spilled some. Before he could wipe it up, the ink solidified, forming a sheet of dry material like paper.

“When I tried to pick it up, it felt strong,” said Jakus, who is now Chief Technology Officer and Co-Founder of Dimension Inx, LLC, a startup also co-founded by Shah. “I knew right then I could make large amounts of bioactive materials from other organs. The light bulb went on in my head. I could do this with other organs.”

A decellularized cow ovary.

Jakus’ lab mishap led to what the Northwestern University team now refers to as “tissue paper” – thin, paperlike sheets that are made from a variety of organ and tissue types. To create the paper, the cells of organs or tissues are removed, leaving the natural structural proteins, known as the extracellular matrix, behind. The proteins are then dried into a powder, combined with a polymer for pliability, and processed into thin sheets. Each different type of tissue paper contains residual biochemicals and protein architecture from the source organ and can stimulate cells to behave in different ways.

For example, in the lab of Teresa Woodruff, who led the mouse ovary study alongside Shah, tissue paper was created from a cow ovary and used to grow ovarian follicles that were cultured in vitro. The follicles grown on the paper were then able to produce hormones.

“This could provide another option to restore normal hormone function to young cancer patients who often lose their hormone function as a result of chemotherapy and radiation,” said Woodruff.

The ovarian tissue paper could potentially be implanted under the arm to restore normal hormone function to women with reduced fertility. That’s only one possible use for the tissue paper, though. According to the research team, the paper could eventually be used to repair organs or muscles during surgery, or even as a bioactive Band-Aid that would facilitate the healing of a wound.

“This new class of biomaterials has potential for tissue engineering and regenerative medicine as well as drug discovery and therapeutics,” said Shah. “It’s versatile and surgically friendly.”

The research was documented in a paper entitled “‘Tissue Papers’ from Organ-Specific Decellularized Extracellular Matrices,” which you can access here. In addition to Shah, Woodruff and Jakus, authors of the study include Monica M. Laronda, Alexandra S. Rashedi, Christina M. Robinson, Chris Lee, Sumanas W. Jordan, and Kyle E. Orwig. Over the course of the study, the researchers created tissue paper made from different types of cow and pig organs including ovaries, uteruses, livers, kidneys, muscles and hearts.

The tissue papers also supported the growth of adult stem cells. At one point, human bone marrow stem cells were placed on the tissue paper, and they all attached and multiplied over the course of four weeks.

According to Jakus, the tissue papers feel and behave a lot like regular office paper when they’re dry – they can be rolled, cut, stacked, and even folded into origami. They also maintain their mechanical properties and function when they’re wet.

“It is really amazing that meat and animal by-products like a kidney, liver, heart and uterus can be transformed into paper-like biomaterials that can potentially regenerate and restore function to tissues and organs,” Jakus said. “I’ll never look at a steak or pork tenderloin the same way again.”

The intellectual property for the tissue paper is owned by Northwestern University and will be licensed to Dimension Inx, which was formed for the purpose of developing, producing and selling 3D printable materials for medical applications. Discuss in the Tissue Paper forum at 3DPB.com.