Elazer Edelman - MIT researchers design tailored tissue adhesives
Glue can be modified for optimal performance in different types of diseased tissue.
Anne Trafton | MIT News Office
January 28, 2015
undergoing surgery to remove diseased sections of the colon, up to 30
percent of patients experience leakage from their sutures, which can
cause life-threatening complications.
Many efforts are under way to create new tissue glues that can help
seal surgical incisions and prevent such complications; now, a new study
from MIT reveals that the effectiveness of such glues hinges on the
state of the tissue in which they are being used.
The researchers found that a sealant they had previously developed
worked much differently in cancerous colon tissue than in colon tissue
inflamed with colitis. The finding suggests that for this sealant or any
other kind of biomaterial designed to work inside the human body,
scientists must take into account the environment in which the material
will be used, instead of using a “one-size fits all” approach, according
to the researchers.
“This paper shows why that mentality is risky,” says Natalie Artzi, a
research scientist at MIT’s Institute for Medical Science and
Engineering (IMES) and senior author of a paper describing the findings
in the Jan. 28 online edition of Science Translational Medicine.
“We present a new paradigm by which to design and examine materials.
Detailed study of tissue and biomaterial interactions can open a new
chapter in precision medicine, where biomaterials are chosen and
rationally designed to match specific tissue types and disease states.”
After characterizing the adhesive material’s performance in different
diseased tissues, the researchers created a model that allows them to
predict how it will work in different environments, opening the door to a
more personalized approach to treating individual patients.
Elazer Edelman, the Thomas D. and Virginia W. Cabot Professor of
Health Sciences and Technology and a member of IMES, is also a senior
author of the paper. The paper’s lead authors are graduate student Nuria
Oliva and former graduate student Maria Carcole.
Exploring material properties
Artzi and Edelman originally developed this tissue glue several years
ago by combining two polymers — dextran (a polysaccharide) and a highly
branched chain called dendrimer. In a 2009 paper,
the researchers demonstrated that such adhesives work better when
tailored to specific organs. In their new paper, they explored what
happens when an adhesive is used in the same organ but under different
They show that the adhesive actually performed better in cancerous
colon tissue than in healthy tissue. However, it performed worse in
tissue inflamed with colitis than in healthy tissue.
Further studies of the molecular interactions between the adhesive
and tissue explained those differences in behavior. The tissue glue
works through a system where molecules in the adhesive serve as “keys”
that interact with “locks” — chemical structures called amines found in
abundance in structural tissue known as collagen.
When enough of these locks and keys bind each other, the adhesive
forms a tight seal. This system is disrupted in colitic tissue because
the inflammation breaks down collagen. The more severe the inflammation,
the less adhesion occurs. However, cancerous tissue tends to have
excess collagen, so the adhesive ends up working better than in healthy
“Now we show that adhesive-material performance is not
organ-dependent, but rather, disease type and state-dependent,” says
Artzi, who is also an assistant professor at Harvard Medical School.
Using this data, the researchers created a model to help them alter
the composition of the material depending on the circumstances. By
changing the materials’ molecular weight, the number of keys attached to
each polymer, and the ratio of the two polymers, the researchers can
tune it to perform best in different types and states of tissue.
An inherent property of the adhesive is that any unused keys are
absorbed back into the polymer, preventing them from causing any
undesired side effects. This would allow the researchers to create two
or three different versions that could cover a wide range of tissues.
“We can take a biopsy from a patient for a quick readout of disease
state that would serve as an input for our model, and the output is the
precise material composition that should be used to attain adequate
adhesion,” Artzi says. “This exercise can be done in a clinical
Joseph Bonventre, chief of the renal unit and director of the
bioengineering division at Brigham and Women’s Hospital in Boston,
agrees that the study represents an important step toward a more
“You want the best adhesive possible, and they really show how
changes in the characteristics of the tissue will alter the adhesive
character,” says Bonventre, who was not involved in the research.
“They’re moving in the direction of doing a quick test in the operating
room and selecting the biomaterial most likely to be effective, rather
than developing biomaterials that try to work for all conditions.”
Doctors have begun using this kind of personalized approach when
choosing drugs that match individual patients’ genetic profiles, but it
has not yet spread to the selection of biomaterials such as tissue glue.
The MIT team now hopes to move the sealant into clinical trials and has
founded a company to help that process along.
“It’s something that we want to do as rapidly as possible,” Edelman
says. “We’re excited. It’s not often that you have a technology that is
this close to clinical introduction.”
The research was funded by the National Institutes of Health and the MIT Deshpande Center for Technological Innovation.