Silk provides the building blocks to transform modern medicine

About a mile northwest of Tufts' Medford/Somerville campus, on the fourth floor of a refurbished woolen factory, there is a shrine to silk. Glass vases filled with silkworm cocoons and washed silk fibers sit artfully on a shelf across from a colorful drawing of the life cycle of Bombyx mori, the domesticated silk moth.

Farther in, more cocoons in wall-mounted cases border a large, close-up image of silk fibers, and displays hold dozens of prototypes made from silk, including smart fabrics, biosensors, a helmet that changes color upon impact, and potential replacements for materials like leather, plastic, and particle board.

The only things missing are the silkworms themselves, but Fiorenzo Omenetto, the director of Silklab and the Frank C. Doble Professor of Engineering at Tufts, said they will be arriving soon. The lab is building a terrarium so that visitors can view the animals.

"We're going to have a celebration of silkworms and moths," Omenetto said.

Silk has been cultivated and harvested for thousands of years. It is best known for the strong, shimmering fabric that can be woven from its fibers, but it also has a long history of use in medicine to dress injuries and suture wounds. At Silklab, Omenetto and his colleagues are building on silk's legacy, proving that this ancient fiber could help create the next generation of biomedical materials.

Silk moth caterpillars, known as silkworms, extrude a single sticky strand of silk from their mouths to form cocoons, which are harvested by silk farmers to make silk thread. At its core, silk is a mixture of two proteins: fibroin, which provides the fiber's structure, and sericin, which binds it together. With a few steps in the lab, Tufts researchers can remove the sericin and dissolve the fibers, turning a dry cocoon into a fibroin-filled liquid.

"Nature builds structural proteins that are very tough and very strong," Omenetto said. "Your bricks are these fibroin proteins floating in water. From there, you can build whatever you want."

Starting with shipments of dried cocoons from silk farms, Omenetto and his colleagues have been able to create gels, sponges, clear plastic-like sheets, printable inks, solids that look like amber, dippable coatings, and much more.

"Each of the materials that you make can contain all these different functions, and there's only 24 hours in a day," Omenetto said with a laugh. "This is why I don't sleep."

New life for recycled silk

For every patterned silk shirt or elegantly draped silk dress worn down a runway, there are dozens of scraps of fabric that were cut away and discarded. Some of those castoffs will find new lives at Silklab.

"At this point, we're getting pallets of very beautiful waste textile—designer waste—that we repurpose into sponges, substitute materials, inks, films, and whatever else," said Fiorenzo Omenetto, the lab's director.

The process the lab uses to break down silk cocoons into liquid proteins works just as well on silk fabric. The presence of dyes means that the liquid silk can't be used for medical or food purposes, but the researchers are finding ways to turn this waste into sustainable replacements for insulation, plastics, and other materials. The goal is to create new materials that work just as well as, if not better than, less sustainable alternatives.

"We're trying to find pragmatic solutions for our planet," Omenetto said. "Just as materials got us into this mess, I truly believe that materials are going to get us out of it."

Biocompatible and biodegradable

When Omenetto arrived at Tufts almost two decades ago, his research was focused on lasers and optics—silk wasn't in the picture. But a chance conversation with David Kaplan, the Stern Family Professor of Engineering and chair of the biomedical engineering department, set him on a new path.

Kaplan, who has been working with silk since the early '90s, was designing a silk scaffold that would help rebuild a person's cornea, allowing cells to grow between the layers. He needed a way to ensure that the growing cells would have enough oxygen and showed the small, transparent sheet to Omenetto, who was immediately intrigued by the material. Omenetto was able to use his lab's lasers to put tiny holes in Kaplan's silk cornea. More collaborations quickly followed.

"We've worked together incessantly since then," Kaplan said.

One of those lines of research has been finding ways to use silk to help repair and regrow bone, blood vessels, nerves, and other tissue. Silk is biocompatible, meaning it doesn't cause harm in the body and breaks down in predictable ways. With the right preparation, silk materials can provide necessary strength and structure while the body is healing.

"You can mold and shape silk to whatever you need, and it will hold that volume while the native tissue regrows into the space and the silk material degrades," Kaplan said. "Eventually it's 100 percent gone, and you're back to your normal tissue."

Some of this work has already been approved for use by the U.S. Food and Drug Administration. A company called Sofregen, which spun out of Kaplan and Omenetto's research, is using an injectable silk-based gel to repair damaged vocal cords, the tissues that regulate air flow and help us speak.

On their own, sturdy silk structures can keep their size, shape, and function for years before degrading. But in some instances, such as those involving surgical screws and plates intended for use in rapidly growing children, this pace would be too slow. The researchers had to find a way to speed up the time it takes for dense silk biomaterials to break down. They introduced an enzyme that our bodies produce naturally into the silk to hasten the breakdown process. The idea is that the enzyme would sit dry and inactive within the silk device until the structure is installed in a person, then the device would hydrate and activate the enzyme to digest the material more rapidly.

"We can titer in just the right amount of enzyme to make a screw go away in a week, a month, a year," Kaplan said. "We have control over the process."

Currently, Kaplan and his lab are working on other small, degradable medical devices that would help cut down on the number of surgeries that patients need. Ear tubes, for example, are often surgically implanted to help alleviate chronic ear infections and then need to be surgically removed. Kaplan and his colleagues have designed silk-based ear tubes that degrade on their own and can even carry antibiotics.

"As someone with a daughter who went through six surgeries on her ear, I know how helpful this could be," Kaplan said.

A stabilizing presence

One of the things that sets silk apart as a material is how benign it is. The liquid mixture the researchers start with is essentially just silk fibroin (the core protein in silk) and water—it's nontoxic and chemically neutral. That means it's easy to add bioactive molecules such as antibiotics or enzymes.

Moreover, silk is remarkably good at stabilizing those molecules and keeping them from degrading. For example, the researchers found that blood samples mixed and dried with silk fibroin remained stable at high temperatures for multiple months. They have had similar findings with vaccines—another spinout company, Vaxess, is currently working to develop silk-based vaccine patches for wide-scale use.

"That's where form and function come into play—you can stabilize a vaccine in the shape of a microneedle patch," Omenetto said. Microneedle patches deliver drugs through needles that are too small to feel. "If you need to distribute vaccines to remote areas where you don't have the luxury of refrigeration, this is really important."

Omenetto is also interested in harnessing the unique properties of dissolved silk proteins to create highly accurate chemical sensors. Silk could hold and preserve the molecules needed to make diagnostic tests or detect potentially harmful bacteria.

"Silk gives shape to the chemistry and maintains the biochemical function of whatever you put inside," Omenetto said. "If you take a molecule and mix it with silk, you can make an ink, a scarf, a flying object, a painting, whatever you like, and the molecule is still active. You can make sensors that have very unusual shapes and a very long shelf life."

One of the items displayed at Silklab is a blue glove with the word "contaminated" printed across its ring finger. The word is written in a silk-based ink that changes color in the presence of specific bacteria. If these inks were printed on food items, they could potentially be used to warn consumers that a product was tainted.

On another shelf, a molded, silk-based sponge carries a protein designed to detect certain viruses. The sponge can be affixed to a drone and flown around to see if there is anything hazardous in the air.

If researchers can design new molecules to detect, say, certain cancers or physiological markers of mental health disorders, these same techniques could turn them into effective and accessible tests, Omenetto said. "These are areas where I think we can help, giving individuals more knowledge and agency."

Silk may also help create better tests for drug-resistant bacteria. As part of a collaboration between Silklab, the Laboratory for Living Devices, and the Stuart B. Levy Center for Integrated Management of Antimicrobial Resistance, Tufts researchers are investigating the possibility of using silk to stabilize various antibiotics in different combinations and doses to get more specific information about how effective they might be against an infection.

"Antimicrobial resistance is a huge problem, and we do not have the right tools to get enough information about specific strains right now," said Bree Aldridge, an associate professor of molecular biology and microbiology at Tufts University School of Medicine who is leading the effort. "With the ability to put material down in patterned ways and to stabilize drugs, we hope to create novel ways of measuring the complex responses of bacteria to drug treatment."

A platform for future research

A number of years ago, Kaplan set his sights on the brain. It's a particularly challenging area to study in humans: Rodent brains aren't a perfect match, cells grown in petri dishes can't capture all of the brain's complexity, and the cells in most three-dimensional models don't typically last more than a few weeks when used in brain-like systems in the lab.

Kaplan hoped that a three-dimensional model built on the right type of silk scaffold could last longer, improving our ability to study diseases, traumatic brain injuries, and other chronic issues. The result, which took six years to perfect, was a porous, donut-shaped silk structure to host growing human brain cells, with axons connecting across a clear gel filling the center. Using this model, the researchers have been able to replicate the physical characteristics of slowly developing diseases like Alzheimer's and Parkinson's. It has already been adopted by several other labs.

"We have a unique and useful model of the brain," Kaplan said. "It's a true tissue-engineered model. We can control what cells we put in, and, when grown correctly, they remain active even after years of continuous culture in the laboratory."

The success of the brain model has led to three-dimensional models of other parts of the body. Collaborating with Ying Chen, a research assistant professor in biomedical engineering, Kaplan helped to build a silk-based model of the intestine. They recently published a paper looking at the cellular effects of ingesting nanoplastics.

"Silk is great for this because it's biologically compatible, but it doesn't tell cells what to do," Kaplan said. "It opens up a way to study these long-term effects and develop treatments."

Kaplan sees many more potential uses for silk throughout medicine and research. He hopes that silk will become a routine medical material, like a more sustainable alternative to plastic, that can be easily shipped and molded for different purposes.

Omenetto agrees, pointing out that the opportunities for silk to improve our lives extend into the food industry, insulation, and many other areas that his lab is exploring. He sees sustainable materials as integral to the efforts of a new university-wide initiative focusing on climate change, which is set to launch this fall with Omenetto as the director. Sometimes, he says, the biggest challenge is simply deciding what to tackle first.

"Having a material that can hold all of these exciting functions, we have to try to decide what's going to be the most impactful," Omenetto said. "If you had all the Lego bricks in the world, what would you build?"

Provided by Tufts University