Joints are designed for hard work. We stand for hours; we lift and bend and open jars with tight lids. We can stay active because healthy cartilage is smooth and squishy enough to withstand daily wear and tear. Unfortunately, cartilage doesn’t stay healthy in everyone.

Tiny defects in cartilage from injury, wear and tear or excessive weight gain, worsen over time. Pain changes how we walk, which in turn, puts too much pressure on the frayed edges of worn cartilage. And when cartilage becomes damaged, it can’t heal on its own, which can lead to osteoarthritis. However, researchers are finding ways to help cartilage heal by mimicking biology in the laboratory.

One group at Case Western Reserve University’s Department of Biomedical Engineering in Cleveland, Ohio, led by Eben Alsberg PhD, associate professor in biomedical engineering and orthopedic surgery, has found a new way to grow sheets of cartilage in a petri dish. The laboratory-grown cartilage (or neocartilage) can potentially be used to fill the “potholes” in damaged cartilage and perhaps prevent osteoarthritis.

Their research was recently published in the Journal of Controlled Release.

Turning cells into cartilage

Growing cartilage or any other tissue in the laboratory is tricky. Cells are accustomed to a particular environment. Researchers trying to raise cells in a petri dish when they’re used to the human body need to figure out the right mix of nutrients and growth conditions that will mimic the cell’s natural environment, a  process that can take weeks of specialized conditions and equipment.

For Alsberg and his team, their goal is to “try to shorten in vitro culture time and simplify the process, to apply this technique to the clinical setting more rapidly,” he says.

The team starts the cartilage making process with mesenchymal stem cells, immature cells from bone marrow that can change into a variety of cell types depending on which nutrients are added. Under the right conditions the mesenchymal stem cells can morph into cartilage cells (chondrocytes), which work like tiny factories to produce matrix, the glue that helps hold cartilage together.
 

For this change to happen, the stem cells need a steady supply of a growth factor such as transforming growth factor-beta 1 (TGF-b-1), a protein that boosts cell growth and helps immature cells morph into chondrocytes. While dumping the growth factor into the petri dish in the beginning and then waiting to see what happens will work, it’s not an optimal way to grow a sheet of cartilage. That’s because once the cartilage tissue begins to expand, the cells would devour all of the growth factor and thus the neocartilage may not be big enough or strong enough to use as replacement tissue.

Alsberg’s group wanted to figure out an effective way to provide the cultures with a steady amount of growth factor. The team turned to tiny gelatin beads called, microspheres. They laced the beads with TGF-b-1 — think Jell-O spiked with nutrients — and added them to the cell cultures.

The spiked beads tricked the cultures of immature cells into thinking they were still inside the body. Chemicals released by the cells slowly degraded the beads, keeping a steady diet of growth factor. The beads also provided a handy structure that stem cells could latch onto on their way to becoming chondrocytes. The space between the microspheres allowed room for the chondrocytes to make the matrix that gives cartilage its bounce and strength. In three weeks, the cartilage was strong enough to handle but not quite as strong as natural cartilage.

One day, Alsberg hopes to use this technique to grow neocartilage for humans, by taking immature cells from each patient, and using those cells in the laboratory to make sheets of cartilage that mimic the strength and bounce of cartilage produced in the body. Then, neocartilage will be transplanted back into the patient, filling any defects, and perhaps halting the cycle of damage that leads to osteoarthritis.
 

Next steps

Moving forward, Alsberg’s team aims to lower the culture time to perhaps one or two weeks and also find ways to make the cartilage as strong as natural tissue.

The team still has work ahead of them. For the neocartilage to work, it will have to be up to the task of weight bearing — efforts that will be tested in animal models before the neocartilage can even reach the stage of clinical trials.

Farshid Guilak PhD, professor of orthopedic medicine at Duke University in Durham, N.C.,  North Carolina is enthusiastic about the research because he says that Alsberg found a delivery method that helps growth factors stay with cells at a constant rate, which could be useful for other applications.

“This work is very exciting because it provides a novel way of delivering the right growth factor over the right time course to produce tissue engineered cartilage,” says Guilak, who is also working on laboratory-grown cartilage.

Guilak, an Arthritis Foundation-funded researcher and his team at Duke and the Massachusetts Institute of Technology use a woven scaffold to grow sheets of cartilage large enough and strong enough to cap the ends of bones. The researchers aim to stave off joint replacement for people with end-stage disease, in which patients have few options other than joint replacement because most of the cartilage is gone.

This work is also in the intermediate stages and undergoing animal testing. Both Guilak and Alsberg say their efforts could be five years from the clinic. Potentially, laboratory-grown cartilage could be used to treat defects in many joints including knees and hips.

“The field of regenerative medicine now is growing at an astounding rate especially in cartilage engineering. I would not be surprised if there are new promising therapies on market in this decade,” says Alsberg.