Lab Grown Cartilage-Bone Grafts Help Rebuild Damaged Joints

Researchers have successfully grown cartilage-bone grafts in the lab that can be used to repair damaged joints such as the jaw.

Although reconstructive surgery is available to treat many joint injuries, it can be imprecise and those who experience such injuries often have to have multiple surgeries and suffer long-term pain and discomfort as a result.

The temporomandibular joint in the jaw is particularly complex to repair and more precise and personalized methods of doing this are needed. If personalized cartilage-bone grafts can be created by using a patient’s own cells then side effects from artificial materials used in prosthetic joints can be minimized and damage can be repaired more effectively and naturally. 

Gordana Vunjak-Novakovic, a professor of dental medicine at Columbia University in New York, and a multi-disciplinary team of researchers are addressing this problem by using cutting edge bioengineering techniques to grow combined cartilage and bone grafts in the lab, which can then be implanted into patients.

“We intentionally selected to regenerate the jaw bone, because its most complex anatomy and very high mechanical loading provided the most stringent test of our technology,” she explained. “If we can address these challenges, then we can also regenerate other parts of the skeleton, and we are moving in this direction.”

The science is still at an early stage and the team tested their technique on a Yucatan minipig model in this study. These pigs are a good model as they have a similar size jaw to humans and the joint undergoes similar levels of mechanical stress. However, the researchers hope to create similar grafts for implantation in people in the near future.

“The clinical validation of this technique, with FDA oversight, is critical for its use in patients,” noted Vunjak-Novakovic.  “epiBone, a company launched from our lab, is now recruiting patients for an initial Phase I/II clinical study that is planned to start in early 2021.”

The grafts were created by first extracting a small sample of fat cells from each animal. This sample was then grown in the lab to increase the number of cells, before triggering some fat cells to change into cartilage cells and some to form bone cells.

To ensure that the implant shape and size was correct, the researchers first built a matrix for the cells to grow on out of sterile bone material sourced from cows. The creation of this framework was guided by imaging so it could exactly fit the shape of the joint. This matrix was then covered in the new bone and cartilage cells, which were left to grow into new tissue.

Growing two types of different tissue that are forming one graft is tricky in the lab. Each tissue type requires slightly different conditions to grow well and a specialized bioreactor chamber was needed to achieve successful growth.

"Developing this one-of-a-kind bioreactor was instrumental for the formation of composite cartilage-bone grafts," said Vunjak-Novakovic. "Each tissue was maintained within its own 'niche,' while allowing communication between cartilage and bone by diffusing factors, just like in our body.”

When the grafts were complete, they were implanted into the pigs (20 in total) and were left to heal for 6 months before the outcomes were assessed.

The results were impressive. The implants had regenerated full-thickness cartilage over the bone and were mechanically stable and strong in comparison to bone only grafts or control grafts that only used the sterile, bone-based matrix.

In addition to being developed as implants to replace damaged tissue, an increasingly common secondary use of lab grown tissue or organs is as a model to test drugs or disease progression on human cells.

Vunjak-Novakovic and colleagues are assessing whether their cartilage-bone grafts could also be used to create an “organ on a chip” to represent joint tissue for use in this kind of testing.