New biomaterial regrows cartilage; could prevent knee replacement surgery

Scientists at Northwestern University have created an innovative bioactive substance capable of regenerating high-quality cartilage in knee joints, demonstrated in a large-animal model.

During their latest research, the team applied this material to the damaged knee cartilage of the animals. Remarkably, within a six-month period, they observed significant repair improvements.

This included the development of new cartilage rich in natural biopolymers like collagen II and proteoglycans, which are crucial for providing pain-free mechanical strength in joints.

“Our new therapy can induce repair in a tissue that does not naturally regenerate. We think our treatment could help address a serious, unmet clinical need,” said Northwestern’s Samuel I. Stupp, the study’s lead author.

Regrowing cartilage

Though it has the appearance of a rubbery substance, this material is actually an intricate network of molecular components that together simulate the natural environment of cartilage in the body.

“Cartilage is a critical component in our joints. When cartilage becomes damaged or breaks down over time, it can have a great impact on people’s overall health and mobility. The problem is that, in adult humans, cartilage does not have an inherent ability to heal,” said Stupp .

This research builds on previous work from the Stupp laboratory, which involved using “dancing molecules” to stimulate human cartilage cells to increase the production of tissue matrix proteins.

In contrast, the current study focuses on a hybrid biomaterial, also developed in Stupp’s lab. This new biomaterial consists of two key elements: a bioactive peptide that binds to transforming growth factor beta-1 (TGFb-1), a crucial protein for cartilage growth and maintenance, and modified hyaluronic acid, a natural polysaccharide found in both cartilage and the lubricating synovial fluid of joints.

Combining peptides and hyaluronic acid

Stupp’s team combined a bioactive peptide with chemically modified hyaluronic acid particles to create nanoscale fiber bundles that mimic cartilage structure. This scaffold was designed to attract the body’s cells to regenerate the tissue. The material’s bioactive signals encourage cells to repair cartilage by populating the scaffold.

“Many people are familiar with hyaluronic acid because it’s a popular ingredient in skincare products,” Stupp said. “It’s also naturally found in many tissues throughout the human body, including the joints and brain. We chose it because it resembles the natural polymers found in cartilage.”

To test its effectiveness, researchers applied the material to cartilage defects in the stifle joints of sheep, which are similar to human knees in structure and mechanical load. This testing was conducted in Mark Markel’s lab at the University of Wisconsin–Madison’s School of Veterinary Medicine.

Injecting the thick, paste-like material into the defects, it formed a rubbery matrix, promoting the growth of new, high-quality cartilage as the scaffold gradually degraded. The new growth consistently showed better quality than the control.

Goodbye to full knee replacements?

Stupp envisions the new material being used in open-joint or arthroscopic surgeries in the future. Currently, the standard procedure is microfracture surgery, which involves creating small fractures in the bone to stimulate new cartilage growth.

With further development, researchers believe this new material could potentially prevent the need for full knee replacements, treat degenerative diseases like osteoarthritis, and repair sports-related injuries such as ACL tears.

“The main issue with the microfracture approach is that it often results in the formation of fibrocartilage — the same cartilage in our ears — as opposed to hyaline cartilage, which is the one we need to have functional joints,” Stupp said .

“By regenerating hyaline cartilage, our approach should be more resistant to wear and tear, fixing the problem of poor mobility and joint pain for the long term while also avoiding the need for joint reconstruction with large pieces of hardware.”

The study has been published in Proceedings of the National Academy of Sciences .