1st May 2017
Success in 3D bioprinting of cartilage
Researchers at Sahlgrenska Academy – part of the University of Gothenburg, Sweden – have generated cartilage tissue by printing stem cells using a 3D-bioprinter.
The fact that the stem cells survived being printed in this manner is a success in itself. In addition, the research team was able to influence the cells to multiply and differentiate to form chondrocytes (cartilage cells) in the printed structure. The findings are published in Scientific Reports.
This research project was a collaboration with scientists at Chalmers University of Technology who are experts in the 3D printing of biological materials, as well as orthopaedic researchers from Kungsbacka.
The team used cartilage cells from patients who had recently undergone knee surgery. These cells were then manipulated in a laboratory, causing them to rejuvenate and revert into "pluripotent" stem cells, i.e. stem cells that have the potential to develop into many different types of cells. The stem cells were then expanded and encapsulated in a composition of nanofibrillated cellulose and printed into a structure using a 3D bioprinter. Following printing, the stem cells were treated with growth factors that caused them to differentiate correctly, so that they formed cartilage tissue.
Credit: 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," says Stina Simonsson, Associate Professor of Cell Biology, who led the research team's three-year effort.
Most of their work involved developing a procedure whereby the cells could survive printing, multiply and then differentiate to form cartilage. One of the key insights gained from their study was that it is necessary to use large amounts of live stem cells to form tissue in this manner.
"We investigated various methods and combined different growth factors," Simonsson explains. "Each individual stem cell is encased in nanocellulose, allowing it to survive the process of being printed into a 3D structure. We also harvested mediums from other cells, which contain the signals that stem cells use to communicate with each other. In layman's terms, our theory is that we managed to trick the cells into thinking that they weren't alone. Therefore the cells multiplied before we differentiated them."
The cartilage formed by stem cells in the 3D bioprinted structure was extremely similar to normal human cartilage. Experienced surgeons who examined the artificial bioprinted tissue saw no difference when they compared it to the real thing, and have stated that the material has properties similar to their patients' natural cartilage. Just like normal cartilage, the lab-grown material contains Type II collagen – and under the microscope, the cells appear to be perfectly formed, with structures similar to those observed in samples of human-harvested cartilage.
This study represents a giant step forward in the ability to generate new, endogenous cartilage tissue. In the not-too-distant future, it should be possible to use 3D bioprinting to generate cartilage based on a patient's own, "backed-up" stem cells. This artificial tissue could then be used to repair cartilage damage, or to treat osteoarthritis, in which joint cartilage degenerates and breaks down. The condition is very common – one in four Swedes over the age of 45 suffer from some degree of osteoarthritis.
In theory, this research has created the opportunity to generate large amounts of cartilage, but one major issue must be resolved before the findings can be used in practice to benefit patients.
"The structure of the cellulose we used might not be optimal for use in the human body," adds 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."
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