This new breed of smart biomaterial could create exciting opportunities in health care, industry, and scientific research. Image: Shyni Varghese
It may jiggle like Jell-o and stick like Velcro, but a new biomaterial developed at the University of California, San Diego (UCSD) is in a class by itself. It's the first permanently cross-linked hydrogel that copies the power of living tissue to heal itself when cut or damaged.
The colorful gelatinous pellets produced in the UCSD lab of Shyni Varghese, Ph.D., look a lot like Jujubes. They're not candy, but there are sweet expectations for their potential in medicine, industry, and science.
Chemically speaking, hydrogels are 3-D networks of cross-linked chains of superabsorbent, hydrophilic polymers. They can be formed from natural or synthetic polymers such as polyvinyl alcohol or sodium polyacrylate, and can be shaped into almost any form. With up to 99.9% water content, their flexibility is similar to human tissue, explaining why they have been used in biomedicine for decades. Soft contact lenses, wound and burn dressings, surgical adhesives, medical implants, and certain time-released drug delivery systems all incorporate the these versatile materials. But as Varghese's breakthrough suggests, this is only the beginning.
According to Varghese, an associate professor of bioengineering in the UCSD Jacobs School of Engineering, her hydrogels derive their self-repairing powers from their unique molecular engineering.
Professor Shyni Varghese. Image: UCSD
Previous attempts to achieve self-healing in hydrogels have been stymied by the presence of water and irreversible molecular cross-links, she said. But using advanced simulation technology, she designed a material made of acryloyl-6-aminocaproic acid (A6ACA) precursors "decorated" with dangling side-chain hydrocarbon molecules to augment the primary molecular structure of the hydrogel network. When segments of these engineered hydrogels come into contact in a low-pH solution, they form a remarkably strong bond in seconds. The same effect also works to close cracks or cuts introduced in a single hydrogel piece.
Researchers describe it as molecular-level Velcro, where these optimized side-chain molecules reach out toward one another across the interface and become entangled, hook-and-loop style. The physical mechanisms result in a durable – even stretchable – bond.
The gels weld and separate easily. Image: UCSD
But Varghese took it one step further. She found that raising pH levels in experimental conditions enabled her to reverse the healing process and, ultimately, control it. By adjusting the solution's pH levels up or down, the pieces weld and separate very easily, she said. "We successfully repeated the process numerous times without any reduction in the weld strength," she said.
The group developed custom tests for determining the tensile strength and other mechanical properties of their hydrogel welds, applying known weights to the healed hydrogels and calculating the engineering stress required to break them. They experimented with various formulations before determining that A6ACA had the best elastomeric properties for self-healing.
"Being bioengineers, one question that repeatedly appeared before us was if one could mimic self-healing in synthetic, tissue-like materials such as hydrogels. The benefits of creating such an aqueous self-healing material would be far-reaching in medicine and engineering," said Varghese.
Because the technology currently requires exposure to low-pH liquid environments, it could lend itself to strong, flexible adhesives or coatings that are useful when it's necessary to repair, withstand, or prevent damage from acidic materials.
One obvious place to seek such applications is the human stomach. The Varghese team is interested in developing new biomedical treatments such as adhesives and drug delivery methods for stomach ulcers and perforations.
In the environmental arena, Varghese sees applications as a rapid sealant to prevent or repair leaks in containers holding corrosive liquids. Self-healing properties could also make possible a new generation of recyclable packaging materials that would reduce industrial and consumer waste.
To broaden the range of applications beyond those that call for acidic conditions, the Varghese team plans to engineer other varieties of hydrogels that self-heal at different pH values.
Self-healing is only one of many engineering innovations under development that could expand the use of hydrogels. Advances in synthetic polymer chemistry, 3-D molecular patterning techniques, and biomimetic rational design approaches are fueling a wave of cutting-edge research around the world, according to Dror Seliktar, a biomedical engineering professor at Technion-Israel Institute of Technology. In his recent review of the field for Science (June 1, 2012, Vol. 336, p. 1124), Seliktar said efforts to engineer hydrogels that are more compatible with the extracellular environment of the body's tissues could push their use in tissue engineering, stem cell research, biosensing, and large-scale protein production.
Michael MacRae is an independent writer.
Being bioengineers, one question that repeatedly appeared before us was if one could mimic self-healing in synthetic, tissue-like materials such as hydrogels.
Prof. Shyni Varghese, University of California, San Diego
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