A sustainable superglue for surgeries

Researchers from Philip Messersmith’s group at the University of California, Berkeley, have developed recyclable adhesives made from a naturally occurring fatty acid that can be tailored for a wide variety of uses—from rigid resins to flexible surgical superglues (Science 2024, DOI: 10.1126/science.ado6292). “We don’t really know of any other adhesive system . . . that can traverse such a wide range of applications,” says Messersmith.

Lipoic acid, a fatty acid enzyme cofactor, has attracted attention from researchers in recent years as a building block for stretchy, self-healing, biodegradable polymers. The disulfide bonds in the polymer backbone make it easy to break down back into the starting material—too easy, in fact. Lipoic acid polymers tend to spontaneously depolymerize when exposed to water, which limits their usefulness.

Subhajit Pal, the postdoctoral fellow who did much of the hands-on work for the paper, devised a solution to keep that depolymerization under control. He added a small amount of lipoic acid monomers that had been modified with N-hydroxysuccinimide esters. The electrophilic esters react with thiols at the end of the polymer chain to prevent them from “backbiting” and triggering depolymerization. They also help accelerate polymerization. As soon as a solution of the monomers in ethanol touches water or a wet surface, it polymerizes into a thick, sticky gel.

By adjusting the monomer ratio and salt content, the researchers altered the polymer properties to create a variety of adhesives, including quick-curing liquid superglues, pressure-sensitive patches, and rigid resins. They also showed that they could break down the pressure-sensitive adhesive using sodium hydroxide, recover high-quality lipoic acid, and use that recovered material to make new polymers.

An important research area in Messersmith’s group is developing surgical glues and patches inspired by mussels’ ability to stick to wet surfaces—a necessary feature for something meant to seal holes in internal organs. The group has been collaborating for over 15 years with researchers at the University Hospital of Zurich to develop materials to help repair incisions from fetal surgery. And he says that the stretchy lipoic acid polymers have “better physical properties for solving that problem than anything that we’ve worked with in the past.”

The researchers demonstrated the material’s surgical-patching potential in pregnant mice by first applying a polymer patch to the gestational sac and then puncturing it with a needle. The materials self-heals to close the hole. All the fetal mice in the patched sacs survived and developed normally, while none of the control mice in unpatched sacs survived.

Mark W. Grinstaff, a professor of biomedical engineering at Boston University who was not involved in the study, called the work “a significant breakthrough in medical adhesive research” that addresses a significant unmet need for glues that are compatible with internal surgery.

Abraham Joy, a professor of bioengineering at Northeastern University, who was not involved in the work, called it a “creative spin” on controlling lipoic acid polymerization. He also praised it for addressing the life cycle of adhesives from sourcing through use and degradation.

The group wants to take several more steps with this material, Messersmith says. On the chemistry end, the team is working on characterizing the polymers more fully and devising new lipoic acid–based monomers to achieve new properties. On the surgical side, Messersmith says they plan to test their new fetal membrane patches in larger animal models and investigate the polymer’s other possible medical uses. “If we can continue to be successful in large animal studies and then ultimately in human clinical studies, I think it could really make a huge impact,” he says.