- 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.
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
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
at the same time with improved wound healing
and strong stable scar.
‘Nature inspired medical glue, to promote better wound healing, could find several applications in future including creating sticky robots and novel drug delivery systems.’
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.
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
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
- 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
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
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
"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."
- 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