Slug Secreted Natural Tissue Adhesive Sticks to Wet Tissues, Improves Wound Healing

Slug Inspired Adhesive Sticks to Wet Tissues, Improves Wound Healing

by Dr. Lakshmi Venkataraman on Jul 31 2017 4:20 PM
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  • The moist environment of the human body poses a major challenge in developing a tissue adhesive that sticks to wet tissues and aids healing.
  • Most adhesives do not stick to wet tissues well and are inflexible when dry, and many are toxic to cells.
  • Novel slug inspired tissue adhesive sticks to wet tissues strongly, at the same time promoting better wound healing and surgical repair.
New medical adhesive that sticks really well to moist tissues, is biocompatible and that aids in better wound healing, has been created by a research team at the Wyss Institute for Biologically Inspired Engineering and the John A. Paulson School of Engineering and Applied Sciences (SEAS) at Harvard University. The research appears in the journal Science.
Search For a Superior Tissue Binding Glue – Unlikely Source of Inspiration

Anyone who has attempted to stick a Band-Aid plaster on a wet skin would have found it highly frustrating to say the least. The story is the same when it comes to developing a tissue adhesive that sticks strongly to the moist tissues within the body or skin, and that also aids in healing and repair of wounds at the same time with improved wound healing and strong stable scar.

In the course of research for such an adhesive, first author of the current study, Jianyu Li, Ph.D. (former Postdoctoral Fellow at the Wyss Institute and now an Assistant Professor at McGill University), stumbled upon a possible solution in an unlikely organism: the humble slug.

The Dusky Arion (Arion subfuscus), occurs commonly in Europe and parts of the United States, and when threatened, secretes a sticky glue that fixes it to the spot making it difficult to be pulled away by the predator.

Physicochemical Properties of the Slug Inspired Adhesive

Earlier studies have found this glue to be composed of a tough matrix peppered with positively charged proteins. This inspired Li and his team to develop a double-layered hydrogel composed of an alginate-polyacrylamide matrix, which in turn supports an adhesive layer that has positively charged polymers protruding from its surface.

The adhesive polymer binds to biological tissues by the following mechanisms resulting in an extremely strong bond that would be difficult to break, namely:
  • Electrostatic attraction to negatively charged cell surfaces
  • Covalent bonds between neighboring atoms, and
  • Physical interpenetration
Li adds that while earlier studies exploring similar solutions have focused only on the polymer based adhesive component that sticks to the tissues, the matrix layer is equally important.

"Most prior material designs have focused only on the interface between the tissue and the adhesive. Our adhesive is able to dissipate energy through its matrix layer, which enables it to deform much more before it breaks."

The current study’s matrix layer includes calcium ions that are bound to the alginate hydrogel via ionic bonds. If great stress is applied to the adhesive, these "sacrificial" ionic bonds will first break first, making the matrix absorb a large amount of energy before the tissue-polymer bond becomes compromised.

Testing the Strength of the Polyacrylamide Matrix Plus Polymer Based Glue
  • The team tested the adhesive on a variety of both dry and wet pig tissues including skin, cartilage, liver, artery and heart, and found that their adhesive was significantly stronger than current medical adhesives.
  • The team further found that more than three times the energy was needed to break the tough adhesive's bonding compared to other medical-grade adhesives and, when the bond did actually break, it was the hydrogel matrix that failed, not the bond between the adhesive and the tissue, exhibiting a high level of simultaneous high tissue adhesion strength as well as matrix toughness.
  • The tough adhesive-tissue bond also remained stable when implanted into rats for two weeks, or when used to plug a hole in a pig heart and the wound strength tested by subjecting it to several rounds of mechanical inflation, deflation and stretching.
  • Most importantly, it caused no tissue damage or adhesions to neighboring tissues when applied to a liver hemorrhage in mice – undesirable side effects that were noted with both a commercial thrombin-based adhesive and super glue.
"The key feature of our material is the combination of a very strong adhesive force and the ability to transfer and dissipate stress, which have historically not been integrated into a single adhesive," says corresponding author Dave Mooney, Ph.D., who is a founding Core Faculty member at the Wyss Institute and the Robert P. Pinkas Family Professor of Bioengineering at SEAS.

Potential Applications of this Tissue Adhesive

Naturally, a strong and stable medical adhesive using a high performance material would find several applications in the medical field including:
  • Use as either a patch that can be cut to desired sizes and applied to body surfaces or as an injectable solution for deeper injuries.
  • To attach medical devices to their target structures, such as an actuator to improve heart function.
"This family of tough adhesives has wide-ranging applications," says co-author Adam Celiz, Ph.D., who is now a Lecturer at the Department of Bioengineering, Imperial College London. "We can make these adhesives out of biodegradable materials, so they decompose once they have served their purpose.
  • Combining this technology with soft robotics to make sticky robots
  • Pharmaceutical applications to make new vehicles for better drug delivery
In conclusion, it is truly amazing how the answers to some of the most challenging problems are found in the most unimaginable places. This study is indeed a shining example.

"Nature has frequently already found elegant solutions to common problems; it's a matter of knowing where to look and recognizing a good idea when you see one," says Wyss Founding Director Donald Ingber, who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children's Hospital, as well as a Professor of Bioengineering at Harvard's School of Engineering and Applied Sciences. "We are excited to see how this technology, inspired by a humble slug, might develop into a new technology for surgical repair and wound healing."

  1. J. Li, A. D. Celiz, J. Yang, Q. Yang, I. Wamala, W. Whyte, B. R. Seo, N. V. Vasilyev, J. J. Vlassak, Z. Suo, D. J. Mooney. Tough adhesives for diverse wet surfaces. Science, 2017; 357 (6349): 378 DOI: 10.1126/science.aah6362