“Dancing” Nanofibers Help Repair Cartilage Damage

A new injectable therapy, which harnesses fast-moving “dancing molecules” to stimulate cellular receptors, could be used to repair damaged cartilage cells, a new study in the Journal of the American Chemical Society, suggests.

What are “dancing molecules”?

“Dancing molecules” is a moniker coined by researchers at Northwestern University for their innovative synthetic nanofibers, formed from molecular assemblies comprising tens to hundreds of thousands of molecules that can interact with cell receptors. By tuning their collective “dancing” motions, Stupp’s team discovered that these nanofibers can rapidly find and engage with the cellular receptors that exist on cell membranes.

“Cellular receptors constantly move around,” said lead study author Samuel I. Stupp, who is the Board of Trustees professor of materials science and engineering, chemistry, medicine and biomedical engineering at Northwestern and the founding director of the Simpson Querrey Institute for BioNanotechnology. “By making our molecules move, ‘dance’ or even leap temporarily out of these structures, known as supramolecular polymers, they are able to connect more effectively with receptors.”

Once injected into the body, the synthetic nanofibers are able to mimic the extracellular matrix structure of their surrounding tissues, mimicking the motion of biological molecules and incorporating bioactive signals for the receptors. In this way, the synthetic materials can communicate with cells.

Previous work led by Stupp’s team at Northwestern had found that this nanofiber could be used therapeutically to regenerate damaged axons and break down scar tissue in mice with severe spinal cord injuries. By injecting the “dancing molecules” into a site close to the mice’s spinal cord, the molecules rapidly triggered spinal cord regeneration, with the animals regaining the ability to walk in just four weeks.

“When we first observed therapeutic effects of dancing molecules, we did not see any reason why it should only apply to the spinal cord,” said Stupp. “Now, we observe the effects in two cell types that are completely disconnected from one another – cartilage cells in our joints and neurons in our brain and spinal cord. This makes me more confident that we might have discovered a universal phenomenon. It could apply to many other tissues.”

Reversing osteoarthritis through cartilage regeneration

Estimates suggest that approximately 528 million people worldwide are affected by osteoarthritis, a degenerative disease that causes connective tissues in the joints to deteriorate over time. This can result in severe joint pain for those affected by the condition and is a leading cause of chronic pain and long-term disability among adults. 

“Current treatments aim to slow disease progression or postpone inevitable joint replacement,” Stupp said. “There are no regenerative options because humans do not have an inherent capacity to regenerate cartilage in adulthood.”

Now, Stupp’s team has applied their “dancing molecule” therapy to human cartilage cells, in order to study whether they might also stimulate growth and repair in this tissue type.

“We are beginning to see the tremendous breadth of conditions that this fundamental discovery on “dancing molecules” could apply to,” Stupp said.

The researchers designed a new circular peptide that mimics the the bioactive signal of transforming growth factor beta-1 (TGFb-1), a protein that plays a critical role in maintaining the homeostasis of cartilage. They then incorporated this peptide into two different molecules that can form supramolecular polymers in water, each with the ability to mimic TGFb-1.

One of these supramolecular polymers was specially designed to enable its molecules to move, or “dance”, more freely within its large assembly, while the other polymer restricted molecular movement.

“We wanted to modify the structure in order to compare two systems that differ in the extent of their motion,” Stupp explained. “The intensity of supramolecular motion in one is much greater than the motion in the other one.”

The team found that while both of the polymers were able to activate the TGFb-1 receptor, the “dancing” polymer was much more effective.

“After three days, the human cells exposed to the long assemblies of more mobile molecules produced greater amounts of the protein components necessary for cartilage regeneration,” Stupp said. “For the production of one of the components in cartilage matrix, known as collagen II, the dancing molecules containing the cyclic peptide that activates the TGFb-1 receptor were even more effective than the natural protein that has this function in biological systems.”

Following the success of their experiments with cartilage cells, Stupp’s team is now testing similar systems in animal studies, working on adding additional signals to create even more bioactive therapies.

Their experiments have had promising early results in regenerating bone, Stupp reported, with a publication expected to follow later in the year. The team is also working with human organoids to test the molecules and accelerate the process of discovering new therapeutic biomaterials.

“With the success of the study in human cartilage cells, we predict that cartilage regeneration will be greatly enhanced when used in highly translational pre-clinical models,” Stupp said. “It should develop into a novel bioactive material for regeneration of cartilage tissue in joints.”

Reference: Yuan SC, Álvarez Z, Lee SR, et al. Supramolecular motion enables chondrogenic bioactivity of a cyclic peptide mimetic of transforming growth factor-β1. J Am Chem Soc. 2024:jacs.4c05170. doi: 10.1021/jacs.4c05170

This article is a rework of a press release issued by Northwestern University. Material has been edited for length and content.