May 23, 2023 – Imagine a day when a simple injection can heal broken bones. When small, ingestible devices remain in the body, unnoticed, tracking our health or delivering life-saving medications. When brain and heart implants intertwine with flesh so seamlessly that the body thinks they were there the whole time.
These are the dreams of materials scientists who have struggled for decades to mimic the intricate structure of the human body in hopes of replacing broken parts or curing disease.
The problem, bioengineers say, is that most replacement and corrective parts—from prostheses to pacemakers—are made of hard, dry, lifeless materials, such as metal or plastic, while biological tissues are soft, moist, and vital.
The body knows the difference and tends to reject imitation.
Enter hydrogels, three-dimensional networks of particles swelled by — by definition — water.
First described in 1960 by the creators of soft contact lenses, these shape-shifting contraptions are capable of transforming from liquid to solid to spongy in the middle. (Early, simple uses include hair gel or gel.) Slow to gain traction, growing to only 1,000 studies published by 1982, it has become the subject of intense study recently, with 100,000 papers published by 2020, and 3,800 already this year alone.
As chemists, biologists, and engineers begin to work with each other and with physicians, the burgeoning field of hydrogels is poised to change the way we take medicines, treat worn joints, and pave the way for a seemingly science-fiction future in what organs, including brains, can interact. directly with the machines.
“We are, basically, a hydrogel,” said Benjamin Wiley, Ph.D., professor of chemistry at Duke University in Durham, North Carolina. “As people develop new hydrogels that closely match the tissues in our bodies, we will be able to treat a whole host of diseases that we couldn’t treat before.”
From contact lenses to brain implants
Simply put, the hydrogel is like a mesh bag of water.
The web is made of polymers, or spaghetti-like strands of molecules, sewn together in a repeating pattern and swelled with H2O, much like the way the 3D matrices in our bodies surround, support, and give structure to our cells and tissues.
“Imagine a soccer net, with all these long fibers woven together to create the net,” said Eric Abel, Ph.D., 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 main ingredient that sets hydrogels apart, making them ideal, as some scientists have called it, for “merging humans and machines.”
Human bones are made up of about 25% water, while muscles hover around 70% and the brain 85%. The precious fluid plays a range of critical roles, from transporting nutrients in and waste to helping cells talk to each other.
Hydrogels made in the lab can be loaded with a cargo (such as a ball in a net), including cells or drugs that help mimic some of these functions.
Hydrogels are also soft and elastic like flesh. Therefore, if they are used in implants, they may be less likely to damage the surrounding tissues.
“Think of a metal spoon in your pudding bowl. When you shake the bowl, the spoon doesn’t stay in place, and you get scarred around the spoon,” said Christina Tringides, a materials scientist who studies neuroengineering. That, she says, is exactly what happens to brain implants when Patients are breathing or moving.” It’s a mechanical mismatch. But with hydrogels, you can get a perfect mechanical match.”
Hydrogels also tend to be non-toxic, so the immune system may be less likely to attack them as foreign bodies.
All of this has made hydrogels the new darling of the bioengineering world.
“There has been an absolute explosion of interest in this material,” said Appel.
Smarter drug delivery and digestible electronics
Early versions of hydrogels were thick and sticky, which made it difficult to get them inside the body.
“Think of a block of Jell-O. You can’t inject something like that,” Abel said.
But Appel, whose lab is developing new drug delivery systems, has been tinkering with gel formulations for years in hopes that one day these high-tech globes can deliver timed drugs to the right place in the body.
New hydrogels start out as fully formed gels (help maintain drug contents) inside a syringe. But once you push the plunger, they magically turn into a liquid thin enough to flow easily through a standard needle. At the exit, they immediately repair gels, protecting the inherent cargo from deterioration.
This could be a game-changer at a time when many cutting-edge drugs — such as Humira for arthritis or Ozempic for type 2 diabetes — are made of rapidly degraded proteins that are too large and complex to fit into a pill. Instead, it must be injected, more often.
“Because the gel takes months to dissolve, it delivers the medicine slowly over time,” said Appel. “You can envision going from a shot once a week to once every 4 months.”
Such slow-release hydrogels could make vaccines last longer, thereby teaching the body to better resist emerging virus variants, and deliver tumor-breaking therapies more precisely, said Abel, who founded a startup and hopes to speed up the first hydrogel drug. Delivery system for clinical trials in a few years.
Meanwhile, another team at MIT took a different approach, developing a standard-sized, ingestible hydrogel pill that swells like a blowfish in the stomach, lasts for a month and slowly releases drugs the entire time. To remove the pill, the patient simply drinks a solution containing salt that dissolves a device the size of a ping-pong ball so that it can be passed outside the body.
in paper in Nature CommunicationsScientists have shown that a puffer fish pill can also be loaded with tiny cameras or monitoring devices to track conditions such as ulcers or cancer.
said Xuanhe Zhao, Ph.D., researcher on the project and associate professor of mechanical engineering at MIT.
Joint building and bone regrowth
Since the 1970s, researchers have considered using hydrogels to replace human cartilage, a remarkably strong and resilient tissue made of about 90 percent water but able to support the weight of a car over an area about the size of a coin.
Until recently, these efforts have largely failed. Meaning, when the knee’s cartilage wears down, things like cartilage transplants, drilling holes to stimulate new growth, or total joint replacement—all of which require lengthy rehabilitation—are the only options.
But maybe it will change.
Wiley and colleagues at Duke recently reported that they’ve developed the first gel-based cartilage replacement that’s stronger and more durable than the real thing.
By attaching their hydrogel to a titanium abutment to help hold it in place, they hope to repair damaged cartilage “like a dentist fills a cavity” long before surgery is necessary.
They’ve also partnered with industry to bring their hydrogels to market—starting with the knees.
“Ultimately, the goal is to work any joint—hips, ankles, fingers, toes,” Willey said.
At the University of Toronto, chemist Karina Carneiro, PhD, and dentist Christopher McCulloch, MD, are also considering it.
In a recent paper in Proceedings of the National Academy of SciencesThey describe a hydrogel, designed by Carneiro and made from DNA, that can be injected, go into a bone defect — an irreparable fracture, a hole from surgery, or a jawbone that has melted with age — and fill in the space like putty. But not only does it patch the hole, it also prompts the bone to regenerate.
In mice that had holes in their skulls caused by surgery, they found that the treatment didn’t work as well as the current gold standard for repairing holes in bone — grafting bone from elsewhere in the body. But it worked.
“These days are very early for DNA hydrogels,” warned McCulloch, a study co-author and professor at the Dental College, noting that it will likely be a decade or more before this technology becomes available to patients. But there is a possibility that DNA hydrogels could one day grow bone without the need for highly invasive surgical procedures. This is great progress.”
science fiction future
Perhaps the wildest and strangest potential applications for hydrogels come in the realm of human-machine interaction.
Several companies are already getting involved in neuroprosthetics or brain-computer interfaces that might one day allow, say, a person who is paralyzed and cannot speak to type on a laptop using their thoughts.
The problem with the spoon in the gel was a major hurdle.
But Tringides, who recently received her PhD in biophysics from Harvard University, is working on it.
She and her team have developed a seaweed-based hydrogel loaded with tiny specks of nanomaterials that can not only mix nicely into the spongy brain tissue, but also conduct electricity.
Within a decade, she says, this could replace the heavy, platinum metal discs used in electrocorticography — the recording of electrical activity in the brain to determine where seizures begin or to perform microsurgery on the brain.
In 30 to 50 years? Let your imagination run wild.
“I’m skeptical. I like to do the research step by step,” she said. “But things are definitely moving in an interesting direction.”