Researchers 3D Print Cartilage with Stem Cells Taken from Human Knee

One of the challenges of 3D bioprinting is getting the stem cells which make up the biological “ink” to survive the 3D printing process – not to mention keeping them viable long enough to grow into a full tissue structure. We hear a lot about the successes of 3D bioprinting, but what we don’t always hear about are the many, many attempts that fail. 3D printing human tissue is no easy endeavor, so every time an advance is made, it’s cause for celebration.

A little over a month ago, a group of Swedish researchers, including several from Sahlgrenska Academy, made big news when they not only implanted 3D printed human cartilage cells into mice, but got them to survive and grow after implantation. The cells were implanted immediately after they were 3D printed, and successfully formed their own blood vessel networks inside the mice, which is a promising step towards the eventual 3D printing and implantation of actual human organs.

Now Sahlgrenska Academy is back in the news for further advances in 3D bioprinting. The team of researchers, working with Chalmers University of Technology, which also collaborated on the previous research, has successfully created cartilage tissue by 3D printing stem cells taken from the human knee. The cells were taken from patients undergoing knee surgery, and after some manipulation in the lab, they reverted into pluripotent stem cells, which can develop into numerous different types of cells.

The cells were then mixed with a solution of nanofibrillated cellulose and 3D printed into predetermined structures. After printing, they were treated with growth hormones that caused them to differentiate and form cartilage tissue. The tissue was the result of three years of work.

Stina Simonsson [Photo: Elin Lindström Claessen]

“In nature, the differentiation of stem cells into cartilage is a simple process, but it’s much more complicated to accomplish in a test tube. We’re the first to succeed with it, and we did so without any animal testing whatsoever,” said Stina Simonsson, Associate Professor of Cell Biology at Sahlgrenska Academy. “We investigated various methods and combined different growth factors. Each individual stem cell is encased in nanocellulose, which allows it to survive the process of being printed into a 3D structure. We also harvested mediums from other cells that contain the signals that stem cells use to communicate with each other so called conditioned medium. In layman’s terms, our theory is that we managed to trick the cells into thinking that they aren’t alone.”

By “tricking” the cells, the research team was able to get them to differentiate before they multiplied. One thing the team learned was that large amounts of stem cells were necessary for the formation of tissue. When the 3D bioprinted cartilage was examined by surgeons, those surgeons found that there was no difference between the 3D printed tissue and naturally occurring human cartilage.

In terms of real-world applications, this breakthrough means that in the near future, it may be possible to 3D print new cartilage in large amounts from patients’ own stem cells. The bioprinted tissue could be used to repair damaged cartilage or treat degenerative conditions such as osteoarthritis. There’s still some work to be done, though.

“The structure of the cellulose we used might not be optimal for use in the human body,” explained Simonsson. “Before we begin to explore the possibility of incorporating the use of 3D bioprinted cartilage into the surgical treatment of patients, we need to find another material that can be broken down and absorbed by the body so that only the endogenous cartilage remains, the most important thing for use in a clinical setting is safety.”

Simonsson is the lead author on a paper detailing the research, entitled “Cartilage Tissue Engineering by the 3D Bioprinting of iPS Cells in a Nanocellulose/Alginate Bioink.” Additional authors include Duong Nguyen, Daniel A. Hägg, Alma Forsman, Josefine Ekholm, Puwapong Nimkingratama, Camilla Brantsing, Theodoros Kalogeropoulos, Samantha Zaunz, Sebastian Concaro, Mats Brittberg, Anders Lindahl, Paul Gatenholm and Annika Enejder. You can read the full study here. Discuss in the 3D Printed Cartilage forum at 3DPB.com.