A new synthetic nanofiber therapy mimics a protein vital for cartilage formation and maintenance. Intensified molecular motion within the nanofibers boosts cartilage regeneration.
Within four hours, the treatment activates gene expression for cartilage growth. Effective in treating osteoarthritis, it shows promise in regenerating cartilage in human cells. The study was published today.
Samuel I Stupp from Northwestern University said, “When we first saw the effects of dancing molecules, we thought they might be useful beyond just spinal cord injuries. We now see similar effects in cartilage cells and neurons, suggesting a universal phenomenon that could apply to many tissues.” Stupp, an expert in regenerative nanomedicine, leads the study with Shelby Yuan, a graduate student.
By 2019, nearly 530 million people worldwide had osteoarthritis, a common and disabling disease where joint tissues break down over time. In severe cases, the cartilage wears thin, leading to painful bone-on-bone contact and loss of joint function.
The only effective treatment is costly, invasive joint replacement surgery. “Current treatments only slow disease progression or delay surgery,” Stupp said. “We lack regenerative options since adults can’t naturally regenerate cartilage.”
Stupp and his team think “dancing molecules” could help regenerate tough tissues. These molecules, created in Stupp’s lab, form synthetic nanofibers that mimic the natural extracellular matrix. These nanofibers can interact effectively with moving cellular receptors by adjusting their motion. “By making our molecules move or ‘dance,’ they connect better with receptors,” Stupp said.
In a new study, Stupp’s team targeted transforming growth factor beta-1 (TGFb-1), a protein critical for cartilage, by creating a circular peptide that mimics it. They incorporated this peptide into two different molecules that form supramolecular polymers. One polymer allowed more molecular movement, while the other restricted it.
Researchers compared two systems with different levels of motion. The polymer with more movement was much more effective at activating the TGFb-1 receptor. After three days, human cells exposed to these mobile molecules produced more proteins needed for cartilage regeneration. The dancing molecules were even more effective than the natural protein at producing collagen II.
Stupp’s team is now testing these systems in animals and adding more signals for highly bioactive therapies.
“With success in human cartilage cells, we predict enhanced cartilage regeneration in pre-clinical models,” Stupp said. “This should become a novel material for joint cartilage regeneration.”
Stupp’s lab is also testing dancing molecules for bone regeneration, and promising results are expected to be published soon. Additionally, they are using human organoids to speed up therapeutic discovery. The team is also seeking FDA approval for clinical trials for spinal cord repair.
“We are discovering the wide range of conditions that ‘dancing molecules’ could treat,” Stupp said. “Controlling supramolecular motion is a powerful tool for many regenerative therapies.”
The study shows that “dancing molecules” can effectively heal cartilage damage. These molecules trigger cartilage regeneration by mimicking natural proteins and enhancing molecular motion. This promising approach could lead to new treatments for joint diseases like osteoarthritis.
Journal refence :
- Shelby C. Yuan, Zaida Álvarez et al., Supramolecular Motion Enables Chondrogenic Bioactivity of a Cyclic Peptide Mimetic of Transforming Growth Factor-β10. Journal of the American Chemical Society. DOI: 10.1021/jacs.4c05170.
Shambhu Kumar is a science communicator, making complex scientific topics accessible to all. His articles explore breakthroughs in various scientific disciplines, from space exploration to cutting-edge research.
