New Lab-Made Cartilage to Rebuild Your Knees Efficiently

Over-the-counter pain relievers, physical therapy, steroid injections — some people have tried it all and are still dealing with knee pain. Often knee pain comes from the progressive wear and tear of cartilage known as osteoarthritis, which affects nearly one in six adults — 867 million people — worldwide. For those who want to avoid replacing the entire knee joint, there may soon be another option that could help patients get back on their feet fast, pain-free, and stay that way.

Writing in the journal Advanced Functional Materials, a Duke University-led team says they have created the first gel-based cartilage substitute that is even stronger and more durable than the real thing. Mechanical testing reveals that the Duke team’s hydrogel — a material made of water-absorbing polymers — can be pressed and pulled with more force than natural cartilage, and is three times more resistant to wear and tearImplants made of the material are currently being developed by Sparta Biomedical and tested in sheep. Researchers are gearing up to begin clinical trials in humans next year.

Duke researchers have developed a gel-based cartilage substitute to relieve achy knees that’s even stronger and more durable than the real thing. Clinical trials to start next year

If everything goes according to plan, the clinical trial should start as soon as April 2023,” said Duke chemistry professor Benjamin Wiley, who led the research along with Duke mechanical engineering and materials science professor Ken Gall.

To make this material, the Duke team took thin sheets of cellulose fibers and infused them with a polymer called polyvinyl alcohol — a viscous goo consisting of stringy chains of repeating molecules — to form a gel. The cellulose fibers act like the collagen fibers in natural cartilage, Wiley said — they give the gel strength when stretched. The polyvinyl alcohol helps it return to its original shape. The result is a Jello-like material, 60% water, which is supple yet surprisingly strong.

Natural cartilage can withstand a whopping 5,800 to 8,500 pounds per inch of tugging and squishing, respectively, before reaching its breaking point. Their lab-made version is the first hydrogel that can handle even more. It is 26% stronger than natural cartilage in tension, something like suspending seven grand pianos from a key ring, and 66% stronger in compression — which would be like parking a car on a postage stamp. “It’s really off the charts in terms of hydrogel strength,” Wiley said.

The team has already made hydrogels with remarkable propertiesIn 2020, they reported that they had created the first hydrogel strong enough for knees, which feel the force of two to three times body weight with each step.


Synthetic Neurons

Synthetic neurons made of hydrogel could one day be used in sophisticated artificial tissues to repair organs such as the heart or the eyes. Hagan Bayley at the University of Oxford and his colleagues devised a synthetic material that can act in a similar way to a human neuron. Made from hydrogel, the artificial neurons are about 0.7 millimetres across ­– about 700 times wider than a human neuron, but similar to giant axons found in squid. They can also be made up to 25 millimetres long, which is similar in length to a human optic nerve running from the eye to the brain.
When a light is shone on the synthetic neuron, it activates proteins that pump hydrogen ions into the cell. These positively charged ions then move through the neuron, carrying an electrical signal. The speed of transmission was too fast to measure with the team’s equipment and is probably faster than the rate in natural neurons, says Bayley. When the positive charge reaches the tip of the neuron, it makes adenosine triphosphate (ATP) – a neurotransmitter chemicalmove from one water droplet to another. In future work, the researchers hope to make the synthetic neuron interact with another via an ATP signal, just as neurons connect with each other at synapses.
The team bundled seven of the neurons together to work in parallel as a synthetic nerve. “This allows us to send multiple signals simultaneously,” says Bayley. “They can all have very different frequencies and so it’s a very versatile signal.” The main purpose is to send different pieces of information down the same pathway, he says.

Artificial nerve cells made from biocompatible materials have been made in a lab for the first time. The innovation may one day be used in synthetic tissues to repair organs such as the heart or the eyes. 

However, the artificial neurons still have a long way to go. Unlike real neurons, there is no mechanism to recycle and create new neurotransmitters in the synthetic system. The neurons therefore only work for a few hours, says Bayley. “The more you do science, the more you find out how clever science is by virtue of evolution.” Alain Nogaret at the University of Bath in the UK says the innovation could play a major role in improving neuro-implants such as artificial retinas by the end of the decade. “The emulation of nervous activity in soft materials is a major step towards non-invasive brain-machine interfaces and solutions addressing neurodegenerative disease.”

Bayley hopes to eventually use these synthetic neurons to deliver different types of drugs simultaneously to treat wounds more quickly and precisely. “Using light, we could maybe release drug molecules in a patterned way,” he says.

How to Keep Cancer from Returning after Surgery

After surgery to remove tumors, some cancer cells can be left behind where they can grow back or spread to a new part of the body. Researchers at the University of Wisconsin-Madison have now developed a hydrogel that can be applied post-surgery to prevent or slow tumor regrowth. The gel works by releasing two compounds selected to strategically keep cancer from coming back after surgery. First is a drug called Pexidartinib, which is already in use to inhibit tumor-associated macrophages (TAMs). These are immune cells that have, for unclear reasons, “switched sides” and now contribute to creating a pro-cancer environment. As such, inhibiting these TAMs slows the growth (or regrowth) of cancer.

A microscope image of the hydrogel (teal) containing platelets with antibodies (red) and tumor-fighting drug nanoparticles (green)

The second component is made up of PD-1 antibodies, which help train T cells to recognize and attack cancer cells. These are bound to platelets for stability. Together, the two components prevent the formation of a microenvironment that’s favorable to cancer growth, and help the immune system clear out any cancer cells remaining after surgery. After its work is done, the gel is designed to biodegrade safely in the body.

The researchers tested the gel in mouse models of several different types of cancers, including colon cancer, melanoma, sarcoma, and triple negative breast cancer. The gel significantly reduced recurrence and metastasis of the cancer, and extended the survival rates of the mice – all control animals succumbed within 36 days, while survival rates ranged between 50 and 66 percent for treated mice, depending on the type of cancer.

The local application of the gel also helps prevent side effects that can arise if a drug is delivered system-wide. As such, no major side effects were seen in the test mice. Importantly, the team says that some of these cancers don’t usually respond well to immune therapy, and are prone to metastasizing, so the effectiveness of the gel treatment is encouraging.

We are really glad to see that this local strategy can work against so many different kinds of tumors, especially these non-immunogenic tumors,” said Quanyin Hu, lead researcher on the study. “We are even more glad to see this local treatment can inhibit tumor metastasis.”


CRISPR Halts Growth of Breast Cancer

Triple-negative breast cancer (TNBC), lacking estrogen, progesterone and HER2 receptors, has the highest mortality rate of all breast cancers. It more frequently strikes women under age 50, African American women, and women carrying a BRCA1 gene mutation. The highly aggressive, frequently metastatic cancer is in urgent need of more effective targeted therapeutics.

A new tumor-targeted CRISPR gene editing system, encapsulated in a nanogel and injected into the body, could offer a genetic treatment, suggest researchers at Boston Children’s Hospital. In a proof-of-principle study, conducted in human tumor cells and live, tumor-bearing mice, the CRISPR system effectively halted the growth of TNBC while sparing normal cells. Peng Guo, PhD,Marsha Moses, PhD and their colleagues have reported the findings in the journal PNAS.

To date, a lack of effective delivery systems has limited the translation of CRISPR gene editing into therapies. One method uses a virus to deliver CRISPR, but the virus cannot carry large payloads and potentially can cause side effects if it “infectscells other than those targeted. Another method packages the CRISPR tools inside a cationic polymer or lipid nanoparticles. But these elements can be toxic to cells, and the body often traps or breaks down the nanoparticles before they reach their destination.

The new approach encapsulates the CRISPR editing system inside a soft “nanolipogel” made up of a nontoxic double layer of fatty molecules and a hydrogel. Antibodies attached to the gel’s surface then guide the CRISPR nanoparticles to the tumor site. (The antibodies are designed to recognize and target ICAM-1, a therapeutic target for TNBC discovered by the Moses Lab in 2014.)

Because the particles are soft and flexible, they can enter cells more efficiently than their stiffer counterparts. Stiffer nanoparticles tend to get trapped by the cell’s ingestion machinery, while the soft particles fused with the tumor cell membrane and delivered their CRISPR payloads directly inside the cell, the researchers found.

Using a soft particle allows us to penetrate the tumor better, without side effects, and with bigger cargo,” says Guo, the study’s first author. “Our system can substantially increase tumor delivery of CRISPR.”