In November 2021, researchers at Northwestern University introduced a new injectable therapy that harnessed fast-moving molecules to repair tissues and reverse paralysis after severe spinal cord injuries. This same research group has now applied the therapeutic strategy to damaged human cartilage cells, activating the gene expression necessary for cartilage regeneration within just four hours. Human cells produced protein components needed for cartilage regeneration after only three days. The effectiveness of the treatment increased as the molecular motion increased, with the molecules’ “dancing” motions being crucial for triggering the cartilage growth process. The study was published in the Journal of the American Chemical Society.
The lead researcher, Samuel I. Stupp, is an expert in regenerative nanomedicine at Northwestern University. As of 2019, nearly 530 million people worldwide were living with osteoarthritis, a degenerative disease in which tissues in joints break down over time. In severe cases, cartilage can wear so thin that joints essentially transform into bone on bone, causing extreme pain and disability. Current treatments aim to slow disease progression or postpone joint replacement surgery, as humans do not have the inherent capacity to regenerate cartilage in adulthood.
Stupp and his team discovered that “dancing molecules” might encourage stubborn tissue like cartilage to regenerate. These synthetic nanofibers mimic the extracellular matrix of surrounding tissue, tuning their collective motions to engage with cellular receptors effectively. By matching the matrix’s structure, mimicking biological molecule motion, and incorporating bioactive signals for receptors, the synthetic materials can communicate with cells. In the new study, the team targeted a specific protein critical for cartilage formation and maintenance, developing a circular peptide to mimic the bioactive signal of the protein, transforming growth factor beta-1 (TGFb-1).
The researchers found that the supramolecular polymer with rapidly moving molecules, mimicking the signal to activate the TGFb-1 receptor, was much more effective at promoting cartilage regeneration in human cells. By enhancing the movement of molecules within the assembly, they were able to produce greater amounts of protein components necessary for cartilage regeneration. Stupp’s team is currently testing these systems in animal studies, adding additional signals to create highly bioactive therapies and is also testing the ability of dancing molecules to regenerate bone with promising early results.
Stupp aims to gain approval for clinical trials to test the therapy for spinal cord repair by building a case to the Food and Drug Administration. The discovery of “dancing molecules” and the ability to control supramolecular motion through chemical design is seen as a powerful tool for increasing efficacy in a range of regenerative therapies. The potential to enhance cartilage regeneration in joints and bone repair opens up new possibilities for treating conditions like osteoarthritis and spinal cord injuries, offering hope for improved outcomes and quality of life for patients with these debilitating conditions.