New Chitosan Adhesive Binds Wet Tissue

Massachusetts Institute of Technology (MIT) researchers demonstrated that their new bio-inspired adhesive tape can tightly bind tissues in and on various surfaces in the body, such as the lungs and intestines within 5 seconds. They expect that this tape could eventually be used in place of presently used surgical sutures.  
“There are over 230 million major surgeries worldwide every year, many of which require sutures to close the wound. These sutures and their corresponding procedures can cause stress on tissues and can cause infections, pain, and scars. We are proposing a fundamentally different approach to sealing tissue,” says Xuanhe Zhao, an associate professor of mechanical engineering and civil and environmental engineering at MIT and the senior author of the study.
The double-sided tape can also be used to attach implantable medical devices to tissues, including the heart, the researchers showed. In addition, it works much faster than tissue glues, which usually take several minutes to bind tightly and can drip onto other parts of the body.

Strong and Lasting Adhesion

Forming a tight seal between tissue surfaces that do not leak or separate is difficult due to bodily fluids which interferes with adhesion. Existing tissue glues diffuse adhesive molecules through the water between two tissue surfaces to bind them together. However this adhesion process can take a long time to take effect.  They may also not seal the spaces between the tissue sufficiently to prevent leakage. They also may not be strong enough to withstand the dynamic and movements of certain tissue like in the heart and intestines.
The MIT team wanted to come up with a solution that would work for all of these problems:

  • Strong sealing capability – no leakage
  • Sealing on wet and moving tissue surfaces
  • Long lasting
  • Biocompatible and biodegradable
Zhao’s group had previously developed other novel adhesives, including a hydrogel superglue that provides tougher adhesion than the sticky materials that occur in nature, such as those that mussels and barnacles use to cling to ships and rocks.  To create a double-sided tape that could rapidly join two wet surfaces together, the team drew inspiration from nature,  specifically, the sticky material that spiders expel to capture their prey.  This natural spider glue includes charged polysaccharides that can absorb water from the surface of an insect almost instantaneously. Clearing/drying off a spot on the insect, the spider releases its glue that adheres to the insect.  To mimic this, the researchers designed an engineered material that first absorbs water from wet tissues and then rapidly binds two tissue surfaces together. For absorption, they used polyacrylic acid, cross-linked with NHS esters.  Once the tape is applied to tissue, its polyacrylic acid enables the tape to instantaneously form weak hydrogen bonds with tissue, and absorb its liquids.  These hydrogen bonds and other biochemical interactions take place holding the tape and tissues in place while the NHS esters help to form strong covalent bonds with proteins in the tissue. This process takes about five seconds.

To enable tensile and long-lasting strength to the tape, either gelatin or
chitosan was used. The chitosan or gelatin can be tuned to adjust its desired resident time and time of biodegradability. Gelatin tends to degrade within a few days or weeks in the human body, whereas chitosan can last much longer (a month or even up to a year).
“This provides a more elegant, more straightforward, and more universally applicable way of introducing an implantable monitor or drug delivery device, because we can adhere to many different sites without causing damage or secondary complications from puncturing tissue to affix the devices,” Yuk says.
This type of adhesive could have a major impact on surgeons’ ability to seal incisions and heal wounds, says, Yuk says. To explore possible applications for the new double-sided tape, the researchers tested it in a few different types of pig tissue, including skin, small intestine, stomach, and liver. They also performed tests in pig lungs and trachea, showing that they could rapidly repair damage to those organs.
“It’s very challenging to suture soft or fragile tissues such as the lung and trachea, but with our double-sided tape, within five seconds we can easily seal them,” Yuk says.
The tape also worked well to seal damage to the gastrointestinal tract, which could be very useful in preventing leakage that sometimes occurs following surgery. This leakage can cause sepsis and other potentially fatal complications.
“I anticipate tremendous translational potential of this elegant approach into various clinical practices, as well as basic engineering applications, in particular in situations where surgical operations, such as suturing, are not straightforward,” says Yu Shrike Zhang, an assistant professor of medicine at Harvard Medical School, who was not involved in the research.
Implanting medical devices within the body is another application the MIT team is exploring. Working with Roche’s lab, the researchers showed that the tape could be used to firmly attach a small polyurethane patch to the hearts of living rats, which are about the size of a thumbnail. Normally this kind of procedure is extremely complicated and requires an experienced surgeon to perform, but the research team was able to simply stick the patch on with their tape by pressing for a few seconds, and it stayed in place for several days.
In addition to the polyurethane heart patch, the researchers found that the tape could successfully attach materials such as silicone rubber, titanium, and hydrogels to tissues. The researchers are now working with doctors to identify additional applications for this kind of adhesive and to perform more tests in animal models.
Study's Researchers
Dual Lead Authors:
Hyunwoo Yuk    – Dept. of Mechanical Engineering, MIT, Cambridge, MA.
Claudia Varela   – Inst. for Medical Engineering and Science, MIT, Cambridge, MA. , Harvard-MIT Program in Health Sciences and Technology, Cambridge, MA.
Other Authors:
Christoph Nabzdyk  – Dept. of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN. ,  Dept. of Anesthesia, Critical Care and Pain Medicine, Mass. General Hospital, Harvard Medical School, Boston, MA.
Xinyu Mao – Dept. of Mechanical Engineering, MIT, Cambridge, MA.
Robert Padera  – Dept. of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA.
Ellen T. Roche  – Dept. of Mechanical Engineering, MIT, Cambridge, MA. ,  Inst. for Medical Engineering and Science, MIT Cambridge, MA. , Harvard-MIT Program in Health Sciences and Technology, Cambridge, MA.
Senior author:
Xuanhe Zhao  – Dept. of Mechanical Engineering, MIT, Cambridge, MA. , Dept.  of Civil and Environmental Engineering, MIT, Cambridge, MA.
The research was funded by the National Science Foundation and the Office of Naval Research. Commercialization of the work is being supported by the MIT Deshpande Center for Technological Innovation.
Study Citation:

Yuk, H., Varela, C.E., Nabzdyk, C.S. et al. Dry double-sided tape for adhesion of wet tissues and devices. Nature 575, 169–174 (2019) doi:10.1038/s41586-019-1710-5

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