Bioprinting Structurally Correct Cartilage Tissue

Cartilage regenerates poorly, and thus injury and wear and tear make joint pin and dysfunction comparatively common conditions. The tissue engineeering of cartilage should provide a basis for regenerative therapies for all such medical issues, but has proven challenging. Researchers have struggled to generate the correct load-bearing structural properties, determined by the arrangement of the extracellular matrix, which is constructed by the cells in response to environmental signals. Here, however, researchers claim success in using a bioprinting approach to build cartilage that closely matches the real thing.

The team used cartilage cells harvested from patients who underwent knee surgery, and 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.

Most of the team's efforts had to do with finding a procedure so that the cells survive printing, multiply and a protocol that works that causes the cells to differentiate to form cartilage. "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." A key insight gained from the team's study is that it is necessary to use large amounts of live stem cells to form tissue in this manner.

The cartilage formed by the stem cells in the 3D bioprinted structure is extremely similar to human cartilage. Experienced surgeons who examined the artificial cartilage saw no difference when they compared the bioprinted tissue to real cartilage, 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.



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