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Apr 28, 2014

Cartilage-on-a-Chip Success Stirs Hopes for Joint Repair

Cartilage-on-a-Chip Success Stirs Hopes for Joint Repair

Among the innovations enabling a new approach to the bioprinting of cartilage is the use of visible light-activated gelation. [Tissue Engineering Part A]

  • Crediting their 3D bioprinting technology, researchers report a significant first: living human cartilage grown on a laboratory chip. The researchers add that this advance brings them closer to their ultimate goal: the creation of replacement cartilage for patients with osteoarthritis or soldiers with battlefield injuries.

    The researchers responsible for this result were led by Rocky Tuan, Ph.D., director of the Center for Cellular and Molecular Engineering at the University of Pittsburgh School of Medicine, member of the American Association of Anatomists.

    According to Dr. Tuan, the creation of artificial cartilage requires three main elements: stem cells, biological factors to make the cells grow into cartilage, and a scaffold to give the tissue its shape. All three elements are provided by his team’s approach, said Dr. Tuan, because it involves the extrusion of thin layers of stem cells embedded in a solution that retains its shape and provides growth factors.

    “We essentially speed up the development process by giving the cells everything they need, while creating a scaffold to give the tissue the exact shape and structure that we want,” explained Dr. Tuan.

    This approach to 3D bioprinting was described April 27 at the Experimental Biology 2014 meeting, during a session entitled Biological and Physical Principles of Matrix-Guided Tissue Engineering. Dr. Tuan’s presentation was called “Biomimetic scaffolds and natural matrices for stem cell-based tissue engineering and modeling.”

    In addition to offering relief for people with osteoarthritis, replacement cartilage could also be a game-changer for people with debilitating joint injuries, such as soldiers with battlefield injuries. “We really want these technologies to help wounded warriors return to service or pursue a meaningful post-combat life,” insisted Dr. Tuan, who co-directs the Armed Forces Institute of Regenerative Medicine, a national consortium focused on developing regenerative therapies for injured soldiers.

    The ultimate vision is to give doctors a tool they can thread through a catheter to print new cartilage right where it’s needed in the patient’s body. This vision may have moved closer to being realized by Dr. Tuan’s method, which uses visible light, unlike previously developed methods, which require UV light, which can be harmful to living cells.

    Dr. Tuan and colleagues described this innovation earlier, in an article that appeared online April 9 in Tissue Engineering Part A, a peer-reviewed journal from Mary Ann Liebert, Inc. In this article, entitled “Cartilage Tissue Engineering Application of Injectable Gelatin Hydrogel with In Situ Visible-Light-Activated Gelation Capability in both Air and Aqueous Solution,” the authors wrote, “We have developed an injectable, biodegradable methacrylated gelatin-based hydrogel capable of rapid gelation via visible light-activated crosslinking in air or aqueous solution. The mild photocrosslinking conditions permitted the incorporation of cells during the gelation process.”

    At the Experimental Biology meeting, Dr. Tuan also reported that his team used the 3D printing method to produce the first tissue-on-a-chip replica of the bone-cartilage interface. Housing 96 blocks of living human tissue four millimeters across by eight millimeters deep, the chip could serve as a test-bed for researchers to learn about how osteoarthritis develops and develop new drugs. “With more testing, I think we’ll be able to use our platform to simulate osteoarthritis, which would be extremely useful since scientists really know very little about how the disease develops,” predicted Dr. Tuan.

    At present, the researchers are working to combine their 3D printing method with a nanofiber spinning technique they developed previously. They hope combining the two methods will provide a more robust scaffold and allow them to create artificial cartilage that even more closely resembles natural cartilage.

    Artificial cartilage built using a patient’s own stem cells could offer enormous therapeutic potential. “We hope that the methods we're developing will really make a difference, both in the study of the disease and, ultimately, in treatments for people with cartilage degeneration or joint injuries,” concluded Dr. Tuan. “Ideally, we would like to be able to regenerate this tissue so people can avoid having to get a joint replacement, which is a pretty drastic procedure and is unfortunately something that some patients have to go through multiple times.”


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