'Biorubber' glue created for faster surgical recovery and pain relief


Date:
August 20, 2020
Source:
Nanyang Technological University
Summary:
Materials scientists have invented a new type of surgical glue
that can help join blood vessels and close wounds faster and may
also serve as a platform to deliver pain relief drugs.



FULL STORY ========================================================================== Materials scientists from Nanyang Technological University, Singapore
(NTU Singapore) have invented a new type of surgical glue that can
help join blood vessels and close wounds faster and may also serve as
a platform to deliver pain relief drugs.


==========================================================================
In a paper published in Elsevier's Biomaterials in July jointly with
clinicians from Singapore General Hospital (SGH), the NTU researchers
showed that their glue can bond soft tissues including muscle and blood vessels, even when their surfaces are wet.

Named CaproGlu, it is activated by a low dose of ultraviolet (UV) light
that cures it in seconds, turning it from a liquid glue into a solid but flexible biorubber -- a biocompatible material that can be resorbed by
the tissue after a few weeks.

The team showed in animal experiments that blood vessels can be rejoined
with just four stitches and a mesh wrapper dipped in CaproGlu, compared to
the usual eight stitches that are required for a reliable and unobstructed join. The authors estimate that this will reduce surgery time by 25 per
cent, as surgeons spend less time and effort stitching up blood vessels
and tissues.

As demonstrated in animal experiments, CaproGlu can also be used to
deliver local anaesthetics or pain relief medication to tissues in the
body, which may be useful both during and after an operation and would
reduce the need for pain relief medication to be administered afterwards.

Unlike current bio-adhesives -- which need two chemicals to be mixed
prior to use -- the CaproGlu is a one-pot liquid gel solution that
comes ready-to-use.



==========================================================================
Lead authors of the paper, Associate Professor Terry W.J. Steele and
Senior Research Fellow Dr Ivan Djordjevic, emphasised that most surgical adhesives available on the market do not work in water or wet environments
as found in the human body.

"To make our light-activated glue work on wet tissues, we engineered our
glue to first remove water from the surface and thus allow adhesion to
the dehydrated surfaces," said Assoc Prof Steele.

"This unique advantage of being able to bond with high strength in a wet environment, as well as being biocompatible, is what makes CaproGlu so
suitable to be used in surgery and medical applications." The adhesion strength of CaproGlu was compared to other commercial bioadhesives on
the market and was found to be three to seven times stronger, and is
on a par with the shear strength of collagen and muscle tissue found in
the human body.

Benefits of CaproGlu Invented by Assoc Prof Steele and Dr Djordjevic
from the NTU School of Materials Science and Engineering, CaproGlu
combines two ingredients into a single-component formulation that does
not require additives.



==========================================================================
The first is polycaprolactone -- a biodegradable polymer which has been approved by the United States Food and Drug Administration for specific applications used in the human body -- and the second: diazirine, a light- sensitive molecule that can form strong bonds when activated.

In their research paper which was published in the scientific journal Biomaterials, the scientists demonstrated how CaproGlu could be used
as part of a new surgical method, where sutures are used in combination
with a glue.

Instead of the conventional eight stitches needed to join the two ends
of a blood vessel in a rabbit, they used four stitches and wrapped
the vessel ends with a biodegradable mesh dipped in CaproGlu and cured
with a small dose of UV light which crosslinked the amino acids on the
tissue's surface As a result, the bleeding from the artery immediately
after the procedure was comparable to what is observed from conventional stitches. When harvested seven days later, the artery was shown to have completely healed.

In a separate experiment, the surgeons inserted CaproGlu loaded with anaesthetics within rats' calves and cured them with UV light before
the wound was closed with conventional stitches.

The scientists compared the activity of these rats with two other
controls: rats who had received anaesthetics alone and rats who had
received CaproGlu without anaesthetics. They found no discernible
impediment of movement for the rats which had anaesthetics and CaproGlu
loaded with anaesthetics, suggesting that CaproGlu is successful in
delivering local anaesthetics over time and could be a useful way to
extend local anaesthesia beyond its current limits and also to act as a
drug delivery platform for medication such as anticoagulants to prevent excessive blood clotting.

The team also observed that there were no discernible side effects to
the animals which had CaproGlu implanted in their skin, which suggested
that it is safe and biocompatible as expected. Since the bioadhesive
dissolves and resorbs within weeks, no follow up clinical visits would
be required for its removal.

Stable shelf life after sterilisation A big challenge for bioadhesives
on the market today is to cope with the standard method by which surgical
grade equipment and disposables are sterilised using gamma irradiation.

The gamma sterilisation process destroys proteins and activates bonding
in both acrylate and epoxy adhesives.

Unlike other surgical adhesives available on the market, CaproGlu's
protein- free formulation exploits new crosslinking chemistry unaffected
by gamma sterilisation.

The light-activated bonding mechanism forms chain links to amino acids
at the nanoscale level, even after several months of storage and gamma sterilisation, thus making CaproGlu's production and commercialisation potentially less costly than those based on proteins and acrylates.

Their biorubber glue innovation took the research team five years to
develop and is the subject of a provisional patent filed through NTUitive,
the university's innovation and enterprise company.

Funding and support for the project include the NTU-Surgery Academic
Clinical Programme Strategic Joint Research Fund, Singapore General
Hospital Research Grant, NTU-Northwestern Institute for Nanomedicine
Grant, NTUitive Proof of Concept (Gap) Fund, A*Star industry Alignment
Fund (Pre-Positioning) and the Ministry of Education Tier 1 & 2 research
fund.

Moving forward, the joint team will be looking to conduct further
animal experiments and to assess the performance of CaproGlu in other applications, such as on bone and other organic surfaces.


========================================================================== Story Source: Materials provided by
Nanyang_Technological_University. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Ivan Djordjevic, Oleksandr Pokholenko, Ankur Harish Shah, Gautama
Wicaksono, Lluis Blancafort, John V. Hanna, Samuel J. Page, Himansu
Sekhar Nanda, Chee Bing Ong, Sze Ryn Chung, Andrew Yuan Hui Chin,
Duncan McGrouther, Jonathan Shunming Teo, Lui Shiong Lee, Terry
W.J. Steele.

CaproGlu: Multifunctional tissue adhesive platform. Biomaterials,
2020; 120215 DOI: 10.1016/j.biomaterials.2020.120215 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200820102419.htm

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