Tag Archives: artificial cartilage

Replacement cartilage grown on laboratory chip

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Most of us don’t think too much about cartilage (soft, flexible connective tissue found in the body) unless it’s damaged in which case it’s importance becomes immediately apparent. There is no substitute for cartilage although scientists are working on that problem and it seems that one team may have made a significant breakthrough according to an April 27, 2014 news item on ScienceDaily,

In a significant step toward reducing the heavy toll of osteoarthritis around the world, scientists have created the first example of living human cartilage grown on a laboratory chip. The researchers ultimately aim to use their innovative 3-D printing approach to create replacement cartilage for patients with osteoarthritis or soldiers with battlefield injuries.

“Osteoarthritis has a severe impact on quality of life, and there is an urgent need to understand the origin of the disease and develop effective treatments” said 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 and the study’s senior investigator. “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.”

Osteoarthritis is marked by a gradual disintegration of cartilage, a flexible tissue that provides padding where bones come together in a joint. Causing severe pain and loss of mobility in joints such as knees and fingers, osteoarthritis is one of the leading causes of physical disability in the United States. It is estimated that up to 1 in 2 Americans will develop some form of the disease in their lifetime.

Although some treatments can help relieve arthritis symptoms, there is no cure. Many patients with severe arthritis ultimately require a joint replacement.

An April 27,2014 Experimental Biology (EB) 2014 news release provides more insight,

Tuan said artificial cartilage built using a patient’s own stem cells could offer enormous therapeutic potential. “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,” said Tuan.

In addition to offering relief for people with osteoarthritis, Tuan said 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,” said Tuan, who co-directs the Armed Forces Institute of Regenerative Medicine, a national consortium focused on developing regenerative therapies for injured soldiers. “We are on a mission.”

Creating 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. Tuan’s 3-D printing approach achieves all three by extruding 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,” said Tuan.

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. Although other researchers have experimented with 3-D printing approaches for cartilage, Tuan’s method represents a significant step forward because it uses visible light, while others have required UV light, which can be harmful to living cells.

In another significant step, Tuan has successfully used the 3-D printing method to produce the first “tissue-on-a-chip” replica of the bone-cartilage interface. Housing 96 blocks of living human tissue 4 millimeters across by 8 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,” said Tuan.

As a next step, the team is working to combine their 3-D 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.

Rocky Tuan presented the research during the Experimental Biology 2014 meeting on Sunday, April 27 [2014].

I haven’t been able to find any papers published on this work but you can find Rocky Tuan’s faculty page (along with a list of publications) here and you may have more luck with the EB 2014 conference website than I did.

New hydrogels make greater elasticity in tissue engineering possible

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A team from Harvard University have developed a technique for creating hydrogels that could be used effective in tissue engineering projects. From the Sept. 5, 2012 news release on EurekAlert,

A team of experts in mechanics, materials science, and tissue engineering at Harvard have created an extremely stretchy and tough gel that may pave the way to replacing damaged cartilage in human joints.

Called a hydrogel, because its main ingredient is water, the new material is a hybrid of two weak gels that combine to create something much stronger. Not only can this new gel stretch to 21 times its original length, but it is also exceptionally tough, self-healing, and biocompatible—a valuable collection of attributes that opens up new opportunities in medicine and tissue engineering.

Here’s an image of the hydrogel provided by the researchers,

The researchers pinned both ends of the new gel in clamps and stretched it to 21 times its initial length before it broke. Credit: Photo courtesy of Jeong-Yun Sun

The Sept. 5, 2012 news item on ScienceDaily has some comments from the researcher,

“Conventional hydrogels are very weak and brittle — imagine a spoon breaking through jelly,” explains lead author Jeong-Yun Sun, a postdoctoral fellow at the Harvard School of Engineering and Applied Sciences (SEAS). “But because they are water-based and biocompatible, people would like to use them for some very challenging applications like artificial cartilage or spinal disks. For a gel to work in those settings, it has to be able to stretch and expand under compression and tension without breaking.”

To create the tough new hydrogel, they combined two common polymers. The primary component is polyacrylamide, known for its use in soft contact lenses and as the electrophoresis gel that separates DNA fragments in biology labs; the second component is alginate, a seaweed extract that is frequently used to thicken food.

Separately, these gels are both quite weak — alginate, for instance, can stretch to only 1.2 times its length before it breaks. Combined in an 8:1 ratio, however, the two polymers form a complex network of crosslinked chains that reinforce one another. The chemical structure of this network allows the molecules to pull apart very slightly over a large area instead of allowing the gel to crack.

The alginate portion of the gel consists of polymer chains that form weak ionic bonds with one another, capturing calcium ions (added to the water) in the process. When the gel is stretched, some of these bonds between chains break — or “unzip,” as the researchers put it — releasing the calcium. As a result, the gel expands slightly, but the polymer chains themselves remain intact. Meanwhile, the polyacrylamide chains form a grid-like structure that bonds covalently (very tightly) with the alginate chains.

Therefore, if the gel acquires a tiny crack as it stretches, the polyacrylamide grid helps to spread the pulling force over a large area, tugging on the alginate’s ionic bonds and unzipping them here and there. The research team showed that even with a huge crack, a critically large hole, the hybrid gel can still stretch to 17 times its initial length.

Importantly, the new hydrogel is capable of maintaining its elasticity and toughness over multiple stretches.

Anyone can see that the ability to stretch, self-heal and stretch mimics the body’s own processes and that materials which can mimic those processes are very promising. From the news item on ScienceDaily,

Beyond artificial cartilage, the researchers suggest that the new hydrogel could be used in soft robotics, optics, artificial muscle, as a tough protective covering for wounds, or “any other place where we need hydrogels of high stretchability and high toughness.”

If you’re interested, there are still more details in the news release on EurekAlert or in the news item on ScienceDaily.