Regenerative Medicine: Cartilage with 'Dancing Molecules' and 'Rubber Liquid'

Two innovative developments from one laboratory restore damaged cartilage. Cartilage tissue can be repaired and grown anew, which is what regenerative medicine is all about. First, using “dancing molecules” to target proteins needed for tissue regeneration, and then using a hybrid biomaterial that acts as a scaffold for cartilage growth.

What does the new branch of regenerative medicine offer?

First study began with the belief that the body has a potential that has not been fully harnessed by nature – the ability to re-grow cartilage. And this can be used to relieve all types of joint pain, including osteoarthritis, and to avoid major surgeries such as total knee reconstruction.

Actions of researchers

Cartilage is a vital component of our joints. When cartilage is damaged or destroyed over time, it has a significant impact on people’s overall health and mobility. The problem is that in adults, cartilage does not have the innate ability to heal. Our new therapy repairs tissue that does not naturally repair itself. We believe our treatment can help address a significant, unmet clinical need.

Lead researcher Samuel Stapp of Northwestern University.

Testing of a hybrid biomaterial that was used back in 2018 for regeneration of sheep jointsfollowed closely on the heels of research using “dancing molecules.” These are synthetic nanofibers containing hundreds of thousands of molecules “charged” with signals for cell growth. Scientists studied their chemical structure to make the molecules “dance,” or move quickly. Stapp and his team found that these molecules can quickly find and interact with cell receptors. Inside the body, the nanofibers align with the extracellular matrix of surrounding tissue and mimic natural cellular communication.

Cell receptors are constantly moving. By making our molecules move, “dance,” or even temporarily jump out of these structures, known as supramolecular polymers, they are able to bind to receptors more effectively.

Lead researcher Samuel Stapp of Northwestern University.

First steps in regeneration

The team designed the ring peptide to then target the protein transforming growth factor beta-1 (TGFb-1), which is found throughout the body and is essential for the growth of cartilage and bone. By comparing the slow-moving molecules to the dancing assembly, the researchers found that the latter was more effective at activating TGFb-1 receptors.

Cartilage cells produce more protein components (collagen II and aggrecan) for regeneration when treated with fast-moving dancing molecules (left) compared to slower-moving molecules. Stapp's research group. Northwestern University

Cartilage cells produce more protein components (collagen II and aggrecan) for regeneration when treated with fast-moving dancing molecules (left) compared to slower-moving molecules. Stapp's research group. Northwestern University

After three days, human cells exposed to the more mobile molecule assemblies produced more of the protein components needed to regenerate cartilage. The dancing molecules, which contained a cyclic peptide that activates the TGF-beta1 receptor, were even more effective at producing one component of the cartilage matrix known as collagen II than the natural protein that performs this function in biological systems.

Lead researcher Samuel Stapp of Northwestern University.

The team is currently testing this system of dancing molecules on regenerating bone, with results to be published later this year. The team also hopes to conduct clinical trials of this development for spinal cord repair. It looks like the world is in for another biohacking tool.

The Second Step of Regenerative Medicine

However, this is not the only discovery of Stapp's lab. second studyInstead of dancing molecules, the team developed a hybrid biomaterial consisting of a bioactive peptide that binds to the all-important protein TGFb-1 and modified hyaluronic acid, a naturally occurring sticky substance that serves as a natural lubricant for the body's bones and joints.

Stimulation of cartilage tissue growth

Many people are familiar with hyaluronic acid because it is a popular ingredient in skin care products. It is also found naturally in many tissues of the human body, including joints and the brain. We chose it because it resembles the natural polymers found in cartilage.

Lead researcher Samuel Stapp of Northwestern University.

The team used this biomaterial to stimulate the organization of fibers into bundles at the nanoscale – mimicking the natural composition of cartilage. In essence, this formed a bio-friendly scaffold that encourages the body’s cells to regenerate cartilage tissue directly on top of it. It will be interesting to see where this advancement will lead, especially with the technology artificial neurons.

This “rubber slime” biomaterial was injected into damaged sheep knee cartilage and within six months the tissue recovered better and new cartilage was observed to grow, consisting of natural collagen II biopolymers and proteoglycans. This resulted in the return of free, painless mobility and effective stability in the previously damaged joint. The new cartilage structure remained strong, while the artificial framework naturally degraded.

Control cartilage (stained with safranin) with defect in upper left corner of image. Samuel I. Stapp/Northwestern University

Control cartilage (stained with safranin) with defect in upper left corner of image. Samuel I. Stapp/Northwestern University

Treated cartilage (stained with safranin) shows the filled defect. Samuel I. Stapp/Northwestern University

Treated cartilage (stained with safranin) shows the filled defect. Samuel I. Stapp/Northwestern University

Transferring technology to humans

The sheep model study accurately predicts how the treatment will work in humans. In other smaller animals, cartilage regeneration occurs much more quickly.

Lead researcher Samuel Stapp of Northwestern University.

The team believes that this thick, paste-like biomaterial could be used in surgery as a less invasive way to stimulate cartilage repair compared to the current microfracture method.

The main problem with the microfracture approach is that it often results in fibrocartilage – the same cartilage found in our ears – rather than the hyaline cartilage we need for functional joints. By regenerating hyaline cartilage, our approach should be more resistant to wear and tear, eliminating long-term joint stiffness and pain, and avoiding the need for joint reconstruction using large metal parts.

Lead researcher Samuel Stapp of Northwestern University.


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