A robust solution for the
efficient repair of wounds in mechanically challenging body areas,
- MeTro, a highly
elastic hydrogel can tightly seal moving tissues without the need for
additional sutures or staples.
- When applied to
an injured lung area in pigs, it bonds and interlocks with the tissue
- It is a novel
solution for the efficient repair of wounds replacing currently used
has been developed
by a team led by Ali Khademhosseini, Ph.D., at Harvard's Wyss
Institute and Nasim Annabi, Ph.D., at Northeastern University.
This study that was recently published in Science
, is a classic example of how human biology can be reengineered to create a broad solution
that can be applied back to patients. The researchers demonstrated how a sealant,
based on a human, resilience-imparting protein called elastin that is present
in all elastic tissues such as the wall of arteries, skin, and lungs can be
photochemically tuned to be used effectively as a surgical sealant
across different tissues and
scales. This highly elastic hydrogel named MeTro can seal incisions in
arteries and lungs of rats and repair wounds in the lungs of pigs, all suture
Sealants with Elastic
surgeons use staples, sutures and wires to bring and hold the wound edges
together until the ruptured or pierced organs and tissues can heal.
procedures have various drawbacks, including and not limited to, difficulty in
sealing back organs and tissues in hard-to-reach areas of the body, not
completely sealing wounds on time, and the risk of further damaging and
‘A highly elastic and adhesive surgical sealant that can effectively seal wounds in moving tissues as well, may soon prove beneficial in humans too.’
become even more challenging to use in wounds in fragile or elastic tissues
that continuously expand or contract and relax, like the breathing lung, the
beating heart and pulsing arteries.
To find a remedy to some of these problems,
biomedical engineers have developed a range of surgical sealants that can bond
tissues to stop leakages. Yet, "currently available sealants are not
suitable for most surgical applications and they do not work alone without the
need for suturing or stapling because they lack an optimal combination of
elasticity, tissue adhesion and strength. Using our expertise in
creating materials for regenerative medicine, we aimed to create an actual fix
for this problem in a multi-disciplinary effort with clinicians and
bioengineers," said Ali Khademhosseini,
The focus of the team was to find a solution in the
lung and other elastic tissues where the problem was most acute.
Inventing the Highly
Earlier, in 2013, Khademhosseini, Annabi and Anthony Weiss, Ph.D., from
the University of Sydney's Charles Perkins Centre and Faculty of Science,
inspired by the natural abilities and synthesis of elastin fibers, had started
to explore the regenerative capabilities of tropoelastin, the precursor
protein from which the body derives functional elastin
. The researchers
learned how to produce large amounts of recombinant human tropoelastin in E. coli
bacteria by mimicking the
They used a
so-called photo-cross-linking reagent named methacrylate and a
pulse of UV light to crosslink different tropoelastin proteins in a solution to
create a versatile highly elastic hydrogel they named MeTro. MeTro can be grown
as tissue constructs to generate a micro-patterned matrix to which heart cells
can adhere, and hence repair cardiac damages.
The next step was
to vary the concentrations of the crosslinking reagent and tropoelastin; the
result was a range of MeTro hydrogels with different elasticities along with
varied cohesive and tissue adhesive strengths
. The compositions of MeTro
that performed best in animal models with lung and vascular injuries were then
identified with the idea of matching them to the tissues' natural elasticities
and strengths and bonding well to tissue surfaces, even in the presence of
fluids like blood.
gels could seamlessly close incisions in arteries and punctures in lungs of
live rats, allowing the animals that otherwise would have succumbed to the
procedure to survive
. "The beauty of a MeTro formulation is that, as
soon as it comes in contact with tissue surfaces, it solidifies into a gel-like
phase without running away. We then can further stabilize it by curing it
on-site with a short light-mediated crosslinking treatment. This allows the
sealant to be very accurately placed and to tightly bond and interlock with
structures on the tissue surface," said Annabi.
Testing MeTro in Pig Lungs
Since pig lung
injuries can be considered akin to human-like lung injuries, MeTro's leak
sealing capacity was tested in explanted and deflated lungs of pigs. When
inflated under higher pressures, MeTro faired far better statistically when
compared to clinically available sealants and sutures.
These results were translated in in-vivo experiments as well, where MeTro could permanently
seal severe pulmonary air and blood leakages, again without applied staples or
. Other important features that were noticed in the in vivo studies
were that MeTro remained stable during the entire period that takes to heal
wounds in demanding mechanical conditions
and the fact that it eventually
degrades without any signs of toxicity. Overall, it is a highly versatile and
efficient surgical sealant that can be used suture and staple-free uses beyond
the pulmonary and vascular systems.
potential applications are powerful, from treating serious internal wounds at
emergency sites such as following car accidents and in war zones, as well as
improving hospital surgeries. We have shown MeTro works in a range of different
settings and solves problems other available sealants can't. We're now ready to
transfer our research into testing on people. I hope MeTro will soon be used in
the clinic, saving human lives." said Weiss.
- N. Annabi el al., "Engineering a highly elastic human protein-based sealant for surgical applications," Science Translational Medicine (2017).