How they are changing healthcare
May 23, 2023 – Imagine a day when a simple injection heals a broken bone. When tiny, ingestible devices linger unnoticed in the body, they monitor our health or deliver life-saving drugs. When brain and heart implants meet flesh so seamlessly that the body thinks they were there all along.
These are the dreams of materials scientists, who have been working for decades to mimic the complex structure of the human body in hopes of replacing broken parts or treating disease.
The problem, bioengineers say, is that most replacement and corrective parts—from prostheses to pacemakers—are made of hard, dry, inanimate materials like metal or plastic, whereas biological tissue is soft, moist, and alive.
The body knows the difference and tends to reject imitations.
Enter hydrogels, three-dimensional networks of molecules swollen, by definition, with water.
These strange, shape-shifting materials were first described in the 1960s by the makers of soft contact lenses, and are capable of changing from liquid to solid. (Early, simple uses include hair gel or Jell-O.). They have slowly gained attention, growing to only 1,000 studies by 1982, and have recently become the subject of intense research. 100,000 papers published in total up to 2020 and 3800 alone this year.
As chemists, biologists and engineers increasingly work with each other and with doctors, the burgeoning field of hydrogels is poised to transform the way we take medicine and treat worn-out joints, paving the way for a future that looks like science fiction. which organs, including the brain, can interact directly with machines.
“We are essentially hydrogels,” said Benjamin Wiley, PhD, professor of chemistry at Duke University in Durham. “As people develop new hydrogels that better fit our body’s tissues, we will be able to treat a range of diseases that we couldn’t treat before.”
From contact lenses to brain implants
Simply put, a hydrogel is like a mesh bag of water.
The mesh consists of polymers or spaghetti-like molecular strands stitched together in a repeating pattern and swollen with H.2Oh, similar to how the 3D matrices in our bodies surround, support and give structure to our cells and tissues.
“Imagine a football net with all these long fibers woven together to create the net,” said Eric Appel, PhD, associate professor of materials science and engineering at Stanford University.
While the broader category of “gels” can be filled with anything, including chemical solvents, water is the key ingredient that sets hydrogels apart, making them ideal for, as some scientists say, “uniting people and machines.”
About 25% of human bones are water, 70% of muscles and 85% of the brain. The precious fluid plays many critical roles, from delivering nutrients and transporting waste products to helping cells talk to each other.
Hydrogels made in the lab can be loaded with cargo (such as a ball in a net), including cells or drugs that help mimic some of these functions.
Hydrogels are soft and pliable like flesh. So, when used in implants, they are less likely to damage the surrounding tissue.
“Think of a metal spoon in the pudding bowl. As you shake the bowl, the spoon doesn’t stay in place and you get scarring around the spoon,” said Christina Tringides, PhD, a materials scientist studying neurosurgery. He says this is exactly what happens with brain implants when the patient breathes or moves. “It’s a mechanical discrepancy. But with hydrogels, a perfect mechanical fit can be achieved.”
Hydrogels are generally non-toxic, so the immune system is less likely to attack them as foreign bodies.
All this has made hydrogels the new favorite of the bioengineering world.
“There has been an absolute explosion of interest in these materials,” Appel said.
Smarter drug delivery and ingestible electronics
Early versions of hydrogels were thick and sticky, making them difficult to get into the body.
“Think of a block of Jell-O.” You can’t administer something like that,” Appel said.
But Appel, whose lab develops new drug delivery systems, has been tinkering with gel formulations for years in the hope that these high-tech spheres could one day deliver time-release drugs to the right place in the body.
Its new hydrogels start out as fully formed gels (which help retain the drug content) in a syringe. But when the piston is pressed, they magically change shape into a liquid so thin that it flows easily through a standard needle. Upon exiting, they immediately turn into a gel, protecting the cargo inside from degradation.
That could be a game-changer at a time when many cutting-edge drugs—think Humira for arthritis or Ozempic for type 2 diabetes—are made up of fast-degrading proteins that are too large and complex to simply fit into a pill. Instead, you need to give injections, often often.
“Because the gel takes months to dissolve, it slowly delivers the drug over time,” Appel said. “It is conceivable that a vaccination once a week could take place once every 4 months.”
Such slow-release hydrogels could extend the life of vaccines, teach the body to better resist emerging virus variants and apply tumor-busting therapies more precisely, said Appel, who founded a startup that hopes to speed up the first hydrogel drug. delivery system into clinical trials within a few years.
Meanwhile, another team at the Massachusetts Institute of Technology took a different approach, developing a standard-sized swallowable hydrogel pill that swells like a flatulence in the stomach, lasts for a month, and slowly releases drugs as it goes. To remove the pill, the patient simply drinks a salt-based solution that shrinks the ping-pong ball-sized device so it can pass out of the body.
In a paper Nature Communicationsscientists have shown that pufferfish pills can be loaded with tiny cameras or monitors to monitor conditions such as ulcers or cancer.
“The dream is to have a Jell-O-like smart pill that stays in the stomach after ingestion and monitors the patient’s health,” said Xuanhe Zhao, PhD, project researcher and associate professor of mechanical engineering at MIT. .
Building joints and regrowing bones
Since the 1970s, researchers have been thinking about replacing human cartilage with hydrogels, an extremely strong and flexible tissue that is about 90% water but can support the weight of a car in an area the size of a coin.
Until recently, these efforts have largely failed. This means that when the cartilage in the knee wears away, the only options are cartilage grafts, drilling holes to encourage new growth, or total joint replacement – all of which require lengthy rehabilitation.
But that may soon change.
Wiley and his colleagues at Duke recently reported that they have developed the first gel-based cartilage substitute that is even stronger and more durable than the real thing.
By attaching the hydrogel to a titanium backing to help it stick in place, they hope to repair damaged cartilage “like a dentist fills a cavity,” well before surgery.
They, too, have partnered with industry to bring their hydrogel to market—starting with knees.
“Ultimately, the goal is to do any joint — hips, ankles, fingers and toes,” Wiley said.
At the University of Toronto, chemist Karina Carneiro (PhD) and dentist Christopher McCulloch (DDS) are also thinking big.
In a recent article Proceedings of the National Academy of Sciences, they describe a hydrogel designed by Carneiro and made of DNA that, when injected, migrates to a bone defect—an irreparable fracture, a surgical hole, or a jawbone that has withered due to age—and fills the gap like putty. But it not only patches the hole, but also stimulates the regeneration of the bone.
In rats with holes in their skulls due to surgery, they found the treatment didn’t work as well as the existing gold standard for repairing bone holes – transplanting bone from elsewhere in the body. But it worked.
“These are very early days for DNA hydrogels,” cautioned McCulloch, a study co-author and professor in the School of Dentistry, noting that it will likely be a decade or more before the technology is available to patients. “But there is the possibility that DNA hydrogel could one day grow bone without the need for highly invasive surgical procedures. This is a significant step forward.”
A sci-fi future
Perhaps the wildest and strangest possible applications of hydrogels are in the realm of human-machine interaction.
Several companies are already working on neural prostheses, or brain-computer interfaces, which could one day, for example, allow someone who is paralyzed and unable to speak to type their thoughts on a laptop.
The spoon-in-the-Jell-O problem was a major stumbling block.
But Tringides, who recently earned a doctorate in biophysics at Harvard, is working on it.
He and his team have developed a seaweed-based hydrogel filled with tiny patches of nanomaterial that not only blends nicely into the limp brain tissue, but also conducts electricity.
Within a decade, he says, it could replace the chunky platinum metal discs used in electrocorticography, which record the brain’s electrical activity to identify where seizures start or perform precise brain surgery.
In 30-50 years? Let your imagination run free.
“I’m skeptical. I like to research step by step,” he said. “But things are definitely moving in an interesting direction.”