May 23, 2023 – Imagine a day when an easy injection speeds the healing of a broken bone. When tiny, ingestible devices remain unnoticed within the body and monitor our health or administer life-saving drugs. When brain and heart implants mix so seamlessly into the flesh that the body thinks they were at all times there.
These are the dreams of materials scientists who’ve worked for many years to duplicate the complex architecture of the human body within the hope of replacing defective parts or curing diseases.
The problem, say bioengineers, is that the majority alternative and corrective parts – from prostheses to pacemakers – are fabricated from hard, dry, lifeless materials reminiscent of metal or plastic, while biological tissue is soft, moist and alive.
The body knows the difference and tends to reject imitations.
This is where hydrogels come into play, three-dimensional networks of molecules which can be – by definition – swollen with water.
First described in 1960 by the inventors of soppy contact lenses, these strange, shape-shifting substances can transform from liquid to solid to a squishy intermediate. (Earlier, easy applications included hair gel or Jell-O.) They were slow to achieve attention, with only one,000 studies published by 1982, but recently they’ve grow to be the topic of intense study, with 100,000 papers will probably be published in total by 2020, and 3,800 this 12 months alone.
As chemists, biologists and engineers increasingly collaborate with one another and with doctors, the emerging field of hydrogels may fundamentally change the way in which we take medications and treat worn-out joints, paving the way in which for a science-fiction-like future wherein organs – including the brain – can interact directly with machines.
“We are essentially hydrogels,” says Dr. Benjamin Wiley, a chemistry professor at Duke University in Durham, North Carolina. “If new hydrogels are developed that better match the tissues in our bodies, we will be able to treat a whole range of diseases that we have not been able to treat before.”
From contact lenses to brain implants
Put simply, a hydrogel is sort of a mesh bag of water.
The mesh consists of polymers or spaghetti-like molecular strands sewn together in a repeating pattern and swollen with H.2O, just like how 3D matrices in our body surround, support and provides structure to our cells and tissues.
“Imagine a soccer net with all these long fibers woven together to form the net,” said Dr. Eric Appel, associate professor of materials science and engineering at Stanford University.
While the broader category of “gels” could be crammed with anything, including chemical solvents, water is the essential ingredient that sets hydrogels apart and makes them ideal for, as some scientists put it, “the fusion of man and machine.”
Human bones are made up of about 25% water, muscles about 70% and the brain 85%. This precious fluid plays plenty of vital roles, from transporting nutrients and waste products to supporting cell communication with one another.
Hydrogels made within the laboratory could be loaded with cargo (like a ball in a net), including cells or drugs that help mimic a few of these functions.
Hydrogels are also soft and pliable like flesh, so when utilized in implants, there may be less risk of harm to surrounding tissue.
“Think of a metal spoon in your pudding bowl. If you shake the bowl, the spoon won't stay in place and scars will form around the spoon,” says Dr. Christina Tringides, a materials scientist who studies neuroengineering. That's exactly what happens, she says, with brain implants when patients breathe or move. “It's a mechanical mismatch. But with hydrogels, you could get a perfect mechanical match.”
Hydrogels are also generally non-toxic, making them less more likely to be attacked by the immune system as foreign bodies.
All this has made hydrogels the brand new darling of biotechnology.
“Interest in these materials has exploded,” said Appel.
Smarter drug delivery and ingestible electronics
Early versions of hydrogels were thick and sticky, making them difficult to manage into the body.
“Think of a block of Jell-O. You couldn't inject something like that,” Appel said.
But Appel, whose lab is developing recent drug delivery systems, has been tinkering with gel formulas for years within the hope that these high-tech lumps could someday deliver timed-release drugs to precisely the appropriate place within the body.
His recent hydrogels start out as fully formed gels (which help preserve drug contents) in a syringe, but once the plunger is pushed, they magically transform right into a liquid thin enough to flow easily through a normal needle. When they exit, they immediately turn back into gels, protecting the cargo inside from disintegration.
This could possibly be crucial at a time when many cutting-edge drugs – reminiscent of Humira for arthritis or Ozempic for type 2 diabetes – are fabricated from rapidly degrading proteins which can be too large and sophisticated to easily put right into a pill. Instead, they need to be injected, and sometimes and sometimes.
“Because the gel takes months to dissolve, it releases the drug slowly over a longer period of time,” said Appel. “You could imagine going from a shot once a week to one every four months.”
Such slow-release hydrogels could extend the shelf lifetime of vaccines and train the body to raised resist recent virus variants. They could also deliver tumor-fighting therapies more precisely, says Appel, who founded a start-up and hopes to bring the primary hydrogel-based drug delivery system into clinical trials inside a number of years.
Meanwhile, one other team on the Massachusetts Institute of Technology has taken a special approach and developed a standard-sized ingestible hydrogel pill that swells up within the stomach like a puffer fish and works for a month, slowly releasing lively ingredients. To remove the pill, the patient simply drinks a saline solution that shrinks the ping-pong ball-sized thing so it might be excreted from the body.
In an article in Nature communicationThe scientists showed that the pufferfish pill may be equipped with tiny cameras or monitors to trace diseases reminiscent of ulcers or cancer.
“The dream is a smart Jell-O-like pill that stays in the stomach after swallowing and monitors the patient's health,” says Dr. Xuanhe Zhao, a researcher involved within the project and an associate professor of mechanical engineering at MIT.
Joint structure and bone growth
Since the Seventies, researchers have been considering using hydrogels to exchange human cartilage, a remarkably strong and versatile tissue that’s about 90% water but can withstand the burden of a automotive in an area concerning the size of a coin.
Until recently, these efforts have been largely unsuccessful. That means when knee cartilage wears down, things like cartilage transplants, drilling holes to stimulate recent growth, or total joint alternative – all of which require lengthy rehabilitation – are the one options.
But that would soon change.
Wiley and his colleagues at Duke recently reported that that they had developed the primary gel-based cartilage substitute that was even stronger and more durable than the unique.
By attaching their hydrogel to a titanium base that higher holds it in place, they hope to repair damaged cartilage, “similar to how a dentist fills a hole,” long before surgery is needed.
They have also partnered with industry to bring their hydrogel to market – starting with the knees.
“Ultimately, the goal is to train every joint – hips, ankles, fingers and toes,” Wiley said.
At the University of Toronto, chemist Dr. Karina Carneiro and dentist Christopher McCulloch DDS even have big goals in mind.
In a recent article in Proceedings of the National Academy of SciencesThey describe a hydrogel developed by Carneiro that’s fabricated from DNA. It could be injected, travels to a bone defect – an irreparable fracture, a hole after surgery, or a jawbone that has atrophied on account of age – and fills the gap like putty. But it doesn't just patch the opening, it also stimulates the regeneration of the bone.
In rats with surgically created holes of their skulls, they found that the treatment didn't work in addition to the prevailing gold standard for repairing holes in bone – transplanting bone from other parts of the body. But it worked.
“DNA hydrogels are still in their early stages,” warns McCulloch, co-author of the study and a professor within the School of Dentistry, noting that it is going to likely be a decade or more before the technology is on the market to patients. “But there is potential that DNA hydrogels could one day grow bone without the need for highly invasive surgical procedures. This is a significant advance.”
A science fiction future
Perhaps the wildest and strangest potential applications of hydrogels are in the world of human-machine interaction.
Many firms are already working on neural prostheses or brain-computer interfaces that would, for instance, someday enable a paralyzed one who cannot speak to write down on a laptop using his or her thoughts.
The problem with the spoon within the jelly was an enormous obstacle.
But Tringides, who recently earned her doctorate in biophysics from Harvard, is working on it.
She and her team have developed a seaweed-based hydrogel enriched with tiny particles of nanomaterials that not only fit well into soft brain tissue but additionally conduct electricity.
Within a decade, she says, this might replace the clunky platinum metal disks utilized in electrocorticography – which records electrical activity within the brain to discover the place to begin of seizures or perform precise brain surgery.
In 30 to 50 years? Let your imagination run wild.
“I'm skeptical. I like to take research step by step,” she said. “But things are definitely moving in an interesting direction.”