* University associate professor Julie Liu, at left, và doctoral student Sydney Hollingshead, prepare to lớn chạy thử a new protein-based adhesive sầu underwater. ( University image/Erin Easterling) Download image

WEST LAFAYETTE, Ind. – A non-toxic glue modeled after adhesive proteins produced by mussels & other creatures has been found to out-perform commercially available products, pointing toward potential surgical glues lớn replace sutures and staples.

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More than 230 million major surgeries are performed worldwide each year, & over 12 million traumatic wounds are treated in the United States alone. About 60 percent of these wounds are closed using mechanical methods such as sutures and staples.

“Sutures và staples have sầu several disadvantages relative khổng lồ adhesives, including patient discomfort, higher risk of infection and the inherent damage to surrounding healthy tissue,” said Julie Liu, an associate professor of chemical engineering và biomedical engineering at University.

Most adhesives vì not work well in moist environments because water interferes with the adhesion process. While developing adhesives that overcome this problem is challenging, glues for medical applications must meet an additional requirement: they must be non-toxic & biocompatible, as well.

“Current biomedical adhesive technologies do not meet these needs,” she said. “We designed a bioinspired protein system that shows promise to lớn achieve sầu biocompatible underwater adhesion coupled with environmentally responsive sầu behavior that is ‘smart,’ meaning it can be tuned khổng lồ suit a specific application.” A YouTube đoạn Clip is available at 

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In efforts khổng lồ develop better alternatives, researchers have been inspired by natural glues. Specifically, underwater application and bonding has been demonstrated with materials based on organisms such as sandcastle worms và mussels. Both produce proteins containing the amino acid 3,4- dihydroxyphenylalanine, or DOPA, which has been shown to provide adhesion strength, even in wet environments.

Retìm kiếm findings were detailed in a research paper published in April in Biomaterials. The paper was authored by graduate student M. Jane Brennan; undergraduate Bridget F. Kilbride; Jonathan Wilker, a professor of chemistry & materials engineering; và Liu.

Current FDA-approved adhesives và sealants face several challenges: many exhibit toxic characteristics, some can only be applied topically because they degrade inlớn carcinogenic products; some are derived from blood sources and carry the potential for blood-borne pathoren transmission such as hepatitis & HIV; và others cause inflammation và irritation.

“More important, however, is that most of these adhesives bởi not possess sufficient adhesion in an excessively wet environment and are not approved for application in wound closure,” Liu said. “In fact, many of these materials specifically advise khổng lồ dry the application area as much as possible.”

The researchers created a new adhesive sầu material called ELY16, an “elastin-like polypeptide,” or ELPhường. It contains elastin, a highly elastic protein found in connective tissue, và tyrosine, an amino acid. The ELY16 was modified by adding the enzyme tyrosinase, converting tyrosine into the adhesive sầu DOPA molecule and forming mELY16.

Both ELY16 and mELY16 are not toxic khổng lồ cells và work well under dry conditions. Modification with DOPA increases adhesion strength in highly humid conditions. Moreover, the modified version is “tunable” to varying environmental conditions và might be engineered khổng lồ match the properties of different tissue types.

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 “To our knowledge, mELY16 provides the strongest bonds of any engineered protein when used completely underwater, & its high yields make it more viable for commercial application compared lớn natural adhesive proteins,” she said. “So it shows great potential lớn be a new smart underwater adhesive.”

The adhesive sầu also has outstanding biocompatibility due lớn the use of human elastin.

Our goal was to mimic the type of adhesion that mussel adhesive sầu proteins have sầu, and much other work has focused on the DOPA molecule as being critical khổng lồ that adhesion,” said Liu. “We found that when the adhesive sầu materials were exposed khổng lồ large amounts of moisture, proteins containing DOPA had a much higher adhesion strength compared lớn unconverted proteins containing only tyrosine. So, DOPA conferred much stronger adhesion in wet environments.”

Testing the adhesive sầu in a highly humid environment is important to determine how well the adhesive will perkhung & cure in the presence of moisture in biomedical applications.

The research showed mELY16 outperformed commercial adhesives including an FDA-approved sealant.

“Compared to this sealant, our proteins with DOPA have significantly higher adhesion strengths,” Liu said.

Elastin-lượt thích polypeptides have the innate ability khổng lồ “coacervate,” which causes them to lớn separate inkhổng lồ “two liquid phases,” one denser and more protein-rich than the other, mimicking the adhesion mechanism used by sandcastle worms.

The elastin provides this coacervation property, which makes possible an easy way to lớn apply the adhesive under water. It’s also a flexible naturally occurring protein found in tissues, và it has been shown that elastin-like polypeptides can be “crosslinked,” or strengthened to lớn change stiffness to mimic soft tissues.

“This elastin-lượt thích polypeptide can be produced in high yields from Escheriphân chia coli & can ‘coacervate’ in response lớn environmental factors such as temperature, pH, & salinity,” she said. “Because the protein will coacervate in a warm liquid bath, a dense protein-rich phase forms. This protein-rich phase contains our adhesive material in concentrated khung, và because it is denser than water, it does not disperse.”

The researchers tested the polymer with mouse cells called NIH/3T3 fibroblasts. These cells are often used in research khổng lồ assess toxiđô thị by examining how well cells survive & grow when exposed lớn new materials. To chạy thử for biocompatibility, the researchers measured the viability of NIH/3T3 fibroblasts cultured for 48 hours directly on a layer of ELY16, mELY16, và a control. In all groups, viability was greater than 95 percent.

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Future research will include work to optimize the formulation of the adhesive sầu and perkhung tests with natural materials.

“We started our tests with aluminum substrates because it is easier khổng lồ achieve sầu reproducible results using aluminum,” Liu said. “However, if we are interested in biomedical applications, we need khổng lồ test substrates that are more similar khổng lồ soft tissues in the body toàn thân, and these substrates are more challenging lớn work with.”

The retìm kiếm was supported by’s Davidson School of Chemical Engineering and the College of Engineering, the National Science Foundation (Awards DMR-1309787 to J.C.L. và J.J.W., CHE- 0952928 lớn J.J.W., and a Graduate Fellowship to M.J.B.), a 3M Nontenured Faculty Award, a Retìm kiếm Foundation Summer Faculty Grant, a Steven C. Beering Fellowship & the Office of Naval Retìm kiếm.