Tag Archives: heart attacks

‘What becomes of the broken-hearted?’ Trinity College Dublin scientists may have an answer

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While Valentine’s Day as celebrated here in Canada and elsewhere (but not everywhere) on February 14 of each year is usually marked in a purely joyous fashion,I’m going to focus on heartbreak. Here is one of the greatest versions of ‘What becomes of the broken-hearted?’ Then, repair follows in the context of some cardiac research coming out of Ireland,

Thank you Joan Osborne and the Funk Brothers. If you haven’t seen ‘Standing in the shadows of Motown’, you may want to make a point of it.

As for the musical question in the headline, researchers at Trinity College Dublin may have an answer of sorts. A February 13, 2020 Trinity College Dublin press release (also on EurekAlert) describes how broken hearts can be mended,

Bioengineers from Trinity College Dublin, Ireland, have developed a prototype patch that does the same job as crucial aspects of heart tissue.

Their patch withstands the mechanical demands and mimics the electrical signalling properties that allow our hearts to pump blood rhythmically round our bodies.

Their work essentially takes us one step closer to a functional design that could mend a broken heart.

One in six men and one in seven women in the EU will suffer a heart attack at some point in their lives. Worldwide, heart disease kills more women and men – regardless of race, than any other disease.

Cardiac patches lined with heart cells can be applied surgically to restore heart tissue in patients who have had damaged tissue removed after a heart attack and to repair congenital heart defects in infants and children. Ultimately, though, the goal is to create cell-free patches that can restore the synchronous beating of the heart cells, without impairing the heart muscle movement.

The bioengineers report their work, which takes us one step closer to such a reality, in the journal Advanced Functional Materials.

Michael Monaghan, ussher assistant professor in biomedical engineering at Trinity, and senior author on the paper, said:

“Despite some advances in the field, heart disease still places a huge burden on our healthcare systems and the life quality of patients worldwide. It affects all of us either directly or indirectly through family and friends. As a result, researchers are continuously looking to develop new treatments which can include stem cell treatments, biomaterial gel injections and assistive devices.”

“Ours is one of few studies that looks at a traditional material, and through effective design allows us to mimic the direction-dependent mechanical movement of the heart, which can be sustained repeatably. This was achieved through a novel method called ‘melt electrowriting’ and through close collaboration with the suppliers located nationally we were able to customise the process to fit our design needs.”

This work was performed in the Trinity Centre for Biomedical Engineering, based in the Trinity Biomedical Sciences Institute in collaboration with Spraybase®, a subsidiary of Avectas Ltd. It was funded by Enterprise Ireland through the Innovation Partnership Program (IPP).

Dr Gillian Hendy, director of Spraybase® is a co-author on the paper. Dr Hendy commended the team at Trinity on the work completed and advancements made on the Spraybase® Melt Electrowriting (MEW) System. The success achieved by the team highlights the potential applications of this novel technology in the cardiac field and succinctly captures the benefits of industry and academic collaboration, through platforms such as the IPP.

Engineering replacement materials for heart tissue is challenging since it is an organ that is constantly moving and contracting. The mechanical demands of heart muscle (myocardium) cannot be met using polyester-based thermoplastic polymers, which are predominantly the approved options for biomedical applications.

However, the functionality of thermoplastic polymers could be leveraged by its structural geometry. The bioengineers then set about making a patch that could control the expansion of a material in multiple directions and tune this using an engineering design approach.

The patches were manufactured via melt electrowriting – a core technology of Spraybase® – which is reproducible, accurate, and scalable. The patches were also coated with the electroconductive polymer polypyrrole to provide electrical conductivity while maintaining cell compatibility.

The patch withstood repeated stretching, which is a dominant concern for cardiac biomaterials, and showed good elasticity, to accurately mimic that key property of heart muscle.

Professor Monaghan added:

“Essentially, our material addresses a lot of requirements. The bulk material is currently approved for medical device use, the design accommodates the movement of the pumping heart, and has been functionalised to accommodate signaling between isolated contractile tissues.”

“This study currently reports the development of our method and design, but we are now looking forward to furthering the next generation of designs and materials with the eventual aim of applying this patch as a therapy for a heart attack.”

Dr Dinorath Olvera, Trinity, first author on the paper, added:

“Our electroconductive patches support electrical conduction between biological tissue in an ex vivo model. These results therefore represent a significant step towards generating a bioengineered patch capable of recapitulating aspects of heart tissue – namely its mechanical movement and electrical signalling.”

Here’s a link to and a citation for the paper,

Electroconductive Melt Electrowritten Patches Matching the Mechanical Anisotropy of Human Myocardium by Dinorath Olvera, Mina Sohrabi Molina, Gillian Hendy, Michael G. Monaghan. Advanced Functional Materials DOI: https://doi.org/10.1002/adfm.201909880 First published: 12 February 2020

This paper is behind a paywall.

Here are links, should you be interested in the company partnering with the researchers, Spraybase®, or its parent company, Avectas Ltd.

Finally, the singer who made ‘What becomes of the broken-hearted?’ a hit in 1965 was Jimmy Ruffin,

Enjoy.

Colliding organic nanoparticles caught on camera for the first time

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There is high excitement about this development in a November 17, 2017 news item on Nanowerk,

A Northwestern University research team is the first to capture on video organic nanoparticles colliding and fusing together. This unprecedented view of “chemistry in motion” will aid Northwestern nanoscientists developing new drug delivery methods as well as demonstrate to researchers around the globe how an emerging imaging technique opens a new window on a very tiny world.

A November 17, 2017 Northwestern University news release (also on EurekAlert) by Megan Fellman, which originated the news item, further illuminates the matter,

This is a rare example of particles in motion. The dynamics are reminiscent of two bubbles coming together and merging into one: first they join and have a membrane between them, but then they fuse and become one larger bubble.

“I had an image in my mind, but the first time I saw these fusing nanoparticles in black and white was amazing,” said professor Nathan C. Gianneschi, who led the interdisciplinary study and works at the intersection of nanotechnology and biomedicine.

“To me, it’s literally a window opening up to this world you have always known was there, but now you’ve finally got an image of it. I liken it to the first time I saw Jupiter’s moons through a telescope. Nothing compares to actually seeing,” he said.

Gianneschi is the Jacob and Rosaline Cohn Professor in the department of chemistry in the Weinberg College of Arts and Sciences and in the departments of materials science and engineering and of biomedical engineering in the McCormick School of Engineering.

The study, which includes videos of different nanoparticle fusion events, was published today (Nov. 1 [2017]7) by the Journal of the American Chemical Society.

The research team used liquid-cell transmission electron microscopy to directly image how polymer-based nanoparticles, or micelles, that Gianneschi’s lab is developing for treating cancer and heart attacks change over time. The powerful new technique enabled the scientists to directly observe the particles’ transformation and characterize their dynamics.

“We can see on the molecular level how the polymeric matter rearranges when the particles fuse into one object,” said Lucas R. Parent, first author of the paper and a National Institutes of Health Postdoctoral Fellow in Gianneschi’s research group. “This is the first study of many to come in which researchers will use this method to look at all kinds of dynamic phenomena in organic materials systems on the nanoscale.”

In the Northwestern study, organic particles in water bounce off each other, and some collide and merge, undergoing a physical transformation. The researchers capture the action by shining an electron beam through the sample. The tiny particles — the largest are only approximately 200 nanometers in diameter — cast shadows that are captured directly by a camera below.

“We’ve observed classical fusion behavior on the nanoscale,” said Gianneschi, a member of Northwestern’s International Institute for Nanotechnology. “Capturing the fundamental growth and evolution processes of these particles in motion will help us immensely in our work with synthetic materials and their interactions with biological systems.”

The National Institutes of Health, the National Science Foundation, the Air Force Office of Scientific Research and the Army Research Office supported the research.

Here’s a link to and a citation for the paper,

Directly Observing Micelle Fusion and Growth in Solution by Liquid-Cell Transmission Electron Microscopy by Lucas R. Parent, Evangelos Bakalis, Abelardo Ramírez-Hernández, Jacquelin K. Kammeyer, Chiwoo Park, Juan de Pablo, Francesco Zerbetto, Joseph P. Patterson, and Nathan C. Gianneschi. J. Am. Chem. Soc., Article ASAP DOI: 10.1021/jacs.7b09060 Publication Date (Web): November 17, 2017

Copyright © 2017 American Chemical Society

This paper is behind a paywall.

Imaging and treating artherosclerosis with a nanoparticle

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For anyone concerned about atherosclerosis (build up of plaque in the arteries) and who doesn’t need immediate assistance, this is encouraging news. A March 14, 2016 news item on ScienceDaily announces research into a nanoparticle that could both image and treat the condition,

Atherosclerosis, a disease in which plaque builds up inside arteries, is a prolific and invisible killer, but it may soon lose its ability to hide in the body and wreak havoc. Scientists have now developed a nanoparticle that functionally mimics nature’s own high-density lipoprotein (HDL). The nanoparticle can simultaneously light up and treat atherosclerotic plaques that clog arteries. Therapy with this approach could someday help prevent deadly heart attacks and strokes.

A March 13, 2016 American Chemical Society (ACS) news release (also on EurekAlert), which originated the news item, expands on the theme,

The researchers present their work today [March 13, 2016] at the 251st National Meeting & Exposition of the American Chemical Society (ACS). …

“Other researchers have shown that if you isolate HDL components from donated blood, reconstitute them and inject them into animals, there seems to be a therapeutic effect,” says Shanta Dhar, Ph.D. “However, with donors’ blood, there is the chance of immunological rejection. This technology also suffers scale-up challenges. Our motivation was to avoid immunogenic factors by making a synthetic nanoparticle which can functionally mimic HDL. At the same time, we wanted a way to locate the synthetic particles.”

Current detection strategies often fail to identify dangerous plaques, which can clog arteries over time or break off from arterial walls and block blood flow, causing a heart attack or stroke. Magnetic resonance imaging (MRI) offers a potential approach for plaque visualization, but requires the use of a contrast agent to show the atherosclerotic plaques clearly. But the potential for harmful immune reactions still exists with the use of donor-derived HDL.

Beyond imaging, there is a therapeutic aspect of using HDL. HDL is widely known as “good” cholesterol because of its ability to pull low-density lipoprotein, or “bad” cholesterol, out of plaques. This process shrinks the plaques, making them less likely to clog arteries or break apart.

To simultaneously identify and treat atherosclerosis without triggering an immune response, Dhar and Bhabatosh Banik, Ph.D., a postdoctoral fellow in her lab, created an MRI-active HDL mimic. The researchers, who are at the University of Georgia, Athens, had previously built synthetic HDL particles lacking a contrast agent. These particles lowered levels of total cholesterol and triglycerides in mice.

“The key challenge, then, was designing the contrast agent,” Banik says. “It took time to figure out the optimal lipophilicity and solubility.” The contrast agent, iron oxide, needs to be encapsulated in the synthetic lipoparticle’s hydrophobic core to provide the brightest possible signal. Eventually, the researchers hit on the right chemical combination — iron oxide with a fatty surface coating — for optimal particle encapsulation. They successfully visualized the contrast agent using MRI in cell studies.

The researchers are applying their synthetic nanoparticle to distinguish between unstable plaques and stationary ones. To do this, Dhar targeted the new MRI-active HDL mimics to macrophages, which are white blood cells that, along with lipids and cholesterol, make up atherosclerotic plaques.

The researchers targeted macrophages by decorating the nanoparticles’ surfaces with a molecule that selectively binds to macrophages. The team observed that the nanoparticles were engulfed by these white blood cells. “Then, when the macrophages ruptured, which is a sign of an unstable plaque, the cells spit out the nanoparticles, causing the MRI signal to change in a detectable fashion,” Banik says.

Dhar says her lab is now using MRI to study how well the particles light up and treat plaques in animals, and she hopes to begin clinical trials within two years. [emphasis mine]

Good luck to the researchers!

Using nanoparticles to prevent ruptures (heart attacks and/or strokes) in artery walls

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This technique from Temple University (Pennsylania, US)  is a long way from ready for general use but it certainly looks promising. From an Oct. 4, 2013 news item on Azonano,

Omar Z. Fisher, assistant professor of bioengineering in Temple’s College of Engineering, has developed a method for linking polyphenols, which are very strong antioxidants, to polymers that can self-assemble into nanoparticles.

Fisher said the project will focus on using these polymers to encapsulate superparamagnetic iron oxide particles (SPIOs), a nano-scale MRI contrasting agent used by his collaborator, Amber Doiron, assistant professor of bioengineering at Binghamton University.

The Oct. 2, 2013 Temple University news release by Preston Moretz, which originated the news item, describes how the nanoparticles will act in the body,

The antioxidant nanoparticles containing the contrasting agent would travel through the blood vessels until they reach atherosclerotic plaque, enabling doctors to diagnose the severity of plaques before they rupture, said Fisher.

“The worse the plaque is, the more likely it is to rupture and give you a clot,” he said. “Because these polymers are made from antioxidants, they are sensitive to oxidative stress, which is more prevalent in more severe plaques.”

Once the oxidative stress destroys the polymers, the MRI contrast agents will be released inside the plaques.

Fisher said doctors would likely prescribe an MRI when a patient was showing some signs of cardiac distress such as fatigue or chest pains.

“During the MRI, the degree of contrast would be visible and indicate to doctors not only that the plaques were there, but the severity of the plaques and how likely they would be to rupture,” he said.

No mention was made of a published paper in either the news item or the news release.