New biomaterial regenerates damaged cartilage in joints

Although it looks like a rubbery slime, the material is actually made up of a complex network of molecular components that work together to mimic the natural environment of cartilage in the body.

In the new study, the researchers applied the material to damaged cartilage in animals' knee joints. Within just six months, the researchers observed evidence of accelerated repair, including the growth of new cartilage containing natural biopolymers (collagen II and proteoglycans) that allow for pain-free mechanical resilience in the joint.

The researchers say that with further study, the new material may one day be used to avoid total knee replacement surgery, treat degenerative diseases such as osteoarthritis, and repair sports-related injuries such as torn anterior cruciate ligaments.

This study Proceedings of the National Academy of Sciences.

“Cartilage is a critical component of joints,” said Northwestern University's Samuel I. Stapp, who led the study. “When cartilage is damaged or degrades over time, it can have a significant impact on people's overall health and ability to move. The problem is that adult cartilage does not have the innate ability to heal. Our novel treatment stimulates the repair of tissue that does not regenerate naturally. We believe our treatment may help address a serious unmet clinical need.”

A pioneer in regenerative nanomedicine, Stapp is a Board Chair Professor of Materials Science and Engineering, Chemistry, Medicine and Biomedical Engineering at Northwestern University and founding director of the university's Simpson Querrey Institute for Bionanotechnology and its affiliated center, the Center for Regenerative Nanomedicine. Stapp is affiliated with the McCormick School of Engineering, the Weinberg School of Letters and Science, and the Feinberg School of Medicine. Jacob Lewis, a doctoral student in Stapp's lab, is lead author on the paper.

What does the material contain?

This new study follows a recently published study from the Stapp lab, in which the team used “dancing molecules” to activate human chondrocytes and promote production of proteins that make up the tissue matrix. Instead of using dancing molecules, the new study will evaluate a hybrid biomaterial developed in the Stapp lab. The new biomaterial consists of two components: a bioactive peptide that binds to transforming growth factor beta 1 (TGFb-1), a protein essential for the growth and maintenance of cartilage, and modified hyaluronic acid, a naturally occurring polysaccharide found in cartilage and in the synovial fluid that lubricates joints.

“Many people are familiar with hyaluronic acid because it's a common ingredient in skin care products,” Stapp says. “Hyaluronic acid is found naturally in many tissues in the human body, including joints and the brain. We chose hyaluronic acid because it is similar to the natural polymer found in cartilage.”

Stapp's team integrated bioactive peptides with chemically modified hyaluronic acid particles to promote the self-organization of nanoscale fibers into bundles that mimic cartilage's natural structure. The goal was to create an attractive scaffold for cells in the body to regenerate cartilage tissue. Using bioactive signals from the nanoscale fibers, the material promotes cartilage repair by cells living in the scaffold.

Clinically important in humans

To evaluate the material's effectiveness at promoting cartilage growth, the researchers tested it in sheep with cartilage defects in their stifles, a complex joint in the hind legs similar to the human knee. The study was conducted in the lab of Mark Markel at the University of Wisconsin-Madison School of Veterinary Medicine.

Testing in a sheep model was crucial, Stapp says: Like in humans, sheep cartilage is tough and very difficult to regenerate, and sheep knee joints share similarities with human knee joints in terms of weight bearing, size and mechanical stresses.

“Studies in sheep models can more accurately predict how the treatment will work in humans,” Stapp said. “In other small animals, cartilage regeneration occurs much more readily.”

In the study, the researchers injected a thick, paste-like material into cartilage defects, which transformed into a rubbery matrix. Not only did new cartilage grow to fill the defect as the scaffold degraded, but the repaired tissue was consistently of higher quality compared to controls.

Permanent solution

Stapp believes that in the future, the new material could be applied to joints during open or arthroscopic surgery. The current standard of care is microfracture surgery, in which surgeons create tiny fractures in the bottom of the bone to encourage new cartilage growth.

“The main problem with microfracture is that it often results in the formation of fibrocartilage, similar to that in the ear, rather than the hyaline cartilage needed for a functional joint,” Stapp says. “By regenerating hyaline cartilage, our method should be more resistant to wear and tear and provide a long-term solution to the problems of reduced mobility and joint pain, while also avoiding the need for large-scale joint reconstruction with instrumentation.”

The study, “Bioactive Supramolecular and Covalent Polymer Scaffolds for Cartilage Repair in a Sheep Model,” was conducted with support from the Mike and Mary Sue Shannon Family Fund for Bioinspired Bioactive Material Systems for Musculoskeletal Regeneration.