Many infants born with heart defects have to undergo repeated surgeries as they grow. Replacing the sutures and staples used in surgery today with fast-acting, biodegradable glues could help make these cardiac procedures faster and safer. Researchers at the Brigham and Women’s Hospital in Boston have developed a surgical glue with promising properties: it doesn’t dissolve in blood, and it’s rubbery enough to hold a seal inside a beating heart.
The cardiac adhesive has been tested in mice and pigs and is being developed as a commercial product by French startup Gecko Biomedical. The Paris-based company, founded by biomaterials researchers in the Boston area, has $11 million in series-A funding, and the company plans to bring the surgical adhesive to patients in Europe in one to two years. The cardiac adhesive is described in a paper published today in the journal Science Translational Medicine.
Sutures and staples have major drawbacks, says Jeffrey Karp, a biomaterials researcher at Brigham and Women’s and one of Gecko Biomedical’s founders. Staples, which work by piercing tissue, can cause damage, and putting in sutures is time consuming. Replacing these tools with rubbery, fast-acting adhesives could help make surgeries faster and less invasive, and potentially prevent complications.
The cardiac adhesive project started when Karp was approached by Boston Children’s Hospital cardiac surgeon Pedro del Nido, who asked him to develop new materials for repairing congenital heart defects. Del Nido had a list of stringent criteria: the material had to not only be very sticky, but biodegradable, able to work in the presence of blood, which can interfere with the action of some glues, and elastic enough to move with the heart.
This is not an easy problem, says Phillip Messersmith, a professor at Northwestern who is not associated with the company or Karp’s research. “Most adhesives that work well under dry conditions are far less effective in the presence of water,” he says. There are medical-grade superglues, but because they contain toxins, they are mainly only used on the skin.
In 2005, Karp developed a stretchy sticky rubber made out of two biomolecules, glycerol and sebacic acid. This material can be applied in a liquid form, and then solidified after a few seconds of exposure to UV light. In its liquid state, it’s viscous and hydrophobic, so it won’t wash away. Karp had previously used this material to make gecko-inspired adhesive tape, hence the company’s name (in 2008 he was named one of MIT Technology Review’s 35 innovators under 35 for this work). Karp has now tuned the polymer’s chemistry to further maximize its underwater adhesiveness. He calls the new glue HLAA, for hydrophobic light-activated adhesive.
Karp worked with del Nido to test the adhesive in animals. HLAA is applied as a liquid goo, then, after about five seconds of exposure to UV light, it hardens into an elastic rubber. Del Nido’s group used HLAA to create a watertight seal repairing heart-wall defects in mice, and to attach patches—used as a surrogate for medical devices that might be attached to the heart—to pigs’ hearts. When the pigs were given adrenaline to increase the heart rate, the patch stayed on. The researchers also used to glue to repair arteries.
Unlike glues that work through a chemical reaction, HLAA works by a physical mechanism. Microscopy studies show that the polymer becomes physically entangled with collagen and other proteins on the tissue surface.
Eric Beckman, a chemical engineer at the University of Pittsburgh, says other companies have tried the UV-light-curing approach in the past, but they had problems. These materials tended to swell up with water and lose strength, becoming like Jell-O. Beckman says Karp’s material is well designed and doesn’t have this problem.
Beckman’s company, Cohera Medical of Pittsburgh, has a product on the market in Europe designed to seal large areas of tissue after mastectomies and tummy tucks, eliminating the need to implant painful drains. Cohera’s glue, which is in the final stages of the U.S. Food and Drug Administration approval process, cures when exposed to water.
There won’t be a one-size-fits-all surgical adhesive, says Beckman. When you go to the hardware store, you find superglue, wood glue, sealants meant for pipes, and many different kinds of adhesives. Beckman expects that once companies get through the expensive medical device approval process, the options for surgeons will be similarly varied. Pending the approval of the European Medical Association, the company hopes to begin clinical tests soon.
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