A new therapy uses synthetic nanofibers to mimic the natural signalling of a protein that is crucial for cartilage formation and maintenance. Scientists found that intensifying the motion of molecules within the nanofibers led to more components needed for regeneration. Experiments have demonstrated that after just four hours, the treatment activated the gene expression necessary to generate cartilage.
The therapy has the potential to be used to treat osteoarthritis, which affects nearly 530 million people worldwide. This is a degenerative disease in which tissues in joints break down over time, osteoarthritis is a common health problem and leading cause of disability.
Back in 2021, Northwestern University researchers, led by Samuel I. Stupp, introduced an injectable new therapy, which harnessed fast-moving “dancing molecules,” to repair tissues and reverse paralysis after severe spinal cord injuries.
Recently, the same research team has applied the therapeutic strategy to damaged human cartilage cells. In the new study, the treatment activated the gene expression necessary to regenerate cartilage within just four hours. And, after only three days, the human cells produced protein components needed for cartilage regeneration.
The researchers also found that, as the molecular motion increased, the treatment’s effectiveness also increased. In other words, the molecules’ “dancing” motions were crucial for triggering the cartilage growth process.
By tuning their collective motions through their chemical structure, the team discovered the moving molecules could rapidly find and properly engage with cellular receptors, which also are in constant motion and extremely crowded on cell membranes.
Once inside the body, the nanofibers mimic the extracellular matrix of the surrounding tissue. By matching the matrix’s structure, mimicking the motion of biological molecules and incorporating bioactive signals for the receptors, the synthetic materials are able to communicate with cells.
For the recent inquiry, the scientists looked to the receptors for a specific protein critical for cartilage formation and maintenance. To target this receptor, the team developed a new circular peptide that mimics the bioactive signal of the protein, which is called transforming growth factor beta-1 (TGFb-1).
Then, the researchers incorporated this peptide into two different molecules that interact to form supramolecular polymers in water, each with the same ability to mimic TGFb-1. The researchers designed one supramolecular polymer with a special structure that enabled its molecules to move more freely within the large assemblies. The other supramolecular polymer, however, restricted molecular movement.
Although both polymers mimicked the signal to activate the TGFb-1 receptor, the polymer with rapidly moving molecules was much more effective. In some ways, they were even more effective than the protein that activates the TGFb-1 receptor in nature.
The study appears in the Journal of the American Chemical Society, titled “Supramolecular motion enables chondrogenic bioactivity of a cyclic peptide mimetic of transforming growth factor-β1.”
