Researchers have developed a new therapy that uses synthetic nanofibers to replicate the natural signaling of a crucial protein involved in the formation and maintenance of cartilage. By enhancing the movement of molecules within these nanofibers, they discovered that more regeneration-building components were produced. Remarkably, this treatment was able to initiate the necessary gene expression for cartilage production in just four hours. This new approach could potentially address osteoarthritis, a condition currently impacting around 530 million individuals worldwide.
In November 2021, researchers from Northwestern University revealed an innovative injectable therapy utilizing fast-moving “dancing molecules” to repair tissues and potentially reverse paralysis caused by severe spinal cord injuries.
This same research team has now adapted this strategy to target damaged human cartilage cells. Their latest study showed that the treatment could activate gene expression essential for cartilage regeneration within only four hours. Furthermore, after just three days, human cells began producing the proteins necessary for cartilage repair.
The team also observed that as the molecular motion increased, so did the effectiveness of the treatment. In essence, the “dancing” motion of the molecules was vital for stimulating the cartilage growth process.
The findings were published today (July 26) in the Journal of the American Chemical Society.
“Initially, when we noted the therapeutic effects of dancing molecules, we didn’t see why it couldn’t be applied beyond spinal cord injuries,” remarked Samuel I. Stupp from Northwestern, the lead researcher. “Now, we see these effects in two entirely different cell types—cartilage cells in our joints and neurons in our brain and spinal cord. This bolsters my belief that we may have uncovered a universal phenomenon applicable to various tissues.”
An expert in regenerative nanomedicine, Stupp is a Board of Trustees Professor across multiple disciplines at Northwestern, where he also directs the Simpson Querrey Institute for BioNanotechnology and the Center for Regenerative Nanomedicine. Shelby Yuan, a graduate student in Stupp’s laboratory, primarily authored the study.
A Significant Challenge with Limited Solutions
The World Health Organization reported that as of 2019, there were nearly 530 million people worldwide suffering from osteoarthritis. This degenerative condition gradually deteriorates joint tissues, making it a common and severe source of disability.
In advanced osteoarthritis cases, the cartilage may deteriorate to the point where joints rub against each other, causing excruciating pain and loss of function. At this stage, the most viable solution is often invasive and costly joint replacement surgery.
“Current treatments focus on slowing the disease progression or postponing the unavoidable need for joint replacement,” Stupp explained. “Regenerative options are lacking because adults do not naturally regenerate cartilage.”
What Exactly Are ‘Dancing Molecules’?
Stupp and his colleagues theorized that “dancing molecules” could stimulate cartilage regeneration. These molecules, previously designed in Stupp’s lab, are synthetic nanofiber assemblies that contain thousands of molecules capable of sending strong signals to cells. By adjusting their motion through changes in their chemical structure, Stupp found that these dynamic molecules could quickly locate and effectively interact with cellular receptors, which are also highly mobile and densely packed on cell membranes.
Once inside the body, the nanofibers imitate the extracellular matrix surrounding tissues. They match the matrix’s structure, emulate biological molecular motion, and carry bioactive signals to communicate effectively with cells.
“Cellular receptors are always in motion,” Stupp noted. “By making our molecules engage in movement, or even temporarily leap from their supramolecular polymer structures, they can connect more proficiently with receptors.”
The Importance of Motion
In their recent research, Stupp’s team targeted a specific receptor crucial for cartilage formation and maintenance. To do this, they created a new circular peptide that mimics the bioactive signal of the protein known as transforming growth factor beta-1 (TGFb-1).
The researchers incorporated this peptide into two different molecules that form supramolecular polymers in water, each designed to mimic TGFb-1. One polymer featured a structure allowing for increased molecular mobility, while the other limited movement.
“We sought to modify the structure to compare two systems differing in their motion extent,” explained Stupp. “The supermolecular motion in one polymer was significantly more pronounced than in the other.”
Despite both polymers mimicking the signal required to activate the TGFb-1 receptor, the rapidly moving molecule polymer proved far more effective, in fact, at some points it surpassed the natural protein’s efficacy.
“After three days, human cells treated with the actively moving molecule assemblies generated higher quantities of the proteins necessary for cartilage regeneration,” Stupp mentioned. “In particular, the assembly containing the cyclic peptide that activates the TGF-beta1 receptor was even more effective than the natural protein responsible for this task in biological systems.”
What Lies Ahead?
Stupp’s team is currently experimenting with these systems in animal models and incorporating additional signals to develop highly bioactive therapies.
“With our success in human cartilage cells, we expect enhanced cartilage regeneration when utilized in advanced pre-clinical models,” Stupp noted. “This has the potential to develop into a novel biocompatible material for cartilage tissue regeneration in joints.”
Additionally, Stupp’s laboratory is testing the effectiveness of dancing molecules in bone regeneration and has already secured promising preliminary results that should be published later this year. At the same time, they are exploring the use of these molecules in human organoids to speed up the discovery and optimization of therapeutic materials.
Stupp’s team is also preparing their case for the Food and Drug Administration, seeking approval to initiate clinical trials for spinal cord repair using this therapy.
“We’re starting to recognize the vast range of conditions that our fundamental discovery of ‘dancing molecules’ could potentially address,” Stupp concluded. “Manipulating supramolecular motion through chemical design seems to offer a powerful approach to enhancing the effectiveness of various regenerative therapies.”
