Tag Archives: heart cells

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

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.

Cyborg organoids?

Every time I think I’ve become inured to the idea of a fuzzy boundary between life and nonlife something new crosses my path such as integrating nanoelectronics with cells for cyborg organoids. An August 9, 2019 news item on ScienceDaily makes the announcement,

What happens in the early days of organ development? How do a small group of cells organize to become a heart, a brain, or a kidney? This critical period of development has long remained the black box of developmental biology, in part because no sensor was small or flexible enough to observe this process without damaging the cells.

Now, researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have grown simplified organs known as organoids with fully integrated sensors. These so-called cyborg organoids offer a rare glimpse into the early stages of organ development.

An August 8, 2019 Harvard John A. Paulson School of Engineering and Applied Sciences news release (also on EurekAlert but published August 9, 2019) by Leah Burrows, which originated the news item, expands on the theme,

“I was so inspired by the natural organ development process in high school, in which 3D organs start from few cells in 2D structures. I think if we can develop nanoelectronics that are so flexible, stretchable, and soft that they can grow together with developing tissue through their natural development process, the embedded sensors can measure the entire activity of this developmental process,” said Jia Liu, Assistant Professor of Bioengineering at SEAS and senior author of the study. “The end result is a piece of tissue with a nanoscale device completely distributed and integrated across the entire three-dimensional volume of the tissue.”

This type of device emerges from the work that Liu began as a graduate student in the lab of Charles M. Lieber, the Joshua and Beth Friedman University Professor. In Lieber’s lab, Liu once developed flexible, mesh-like nanoelectronics that could be injected in specific regions of tissue.

Building on that design, Liu and his team increased the stretchability of the nanoelectronics by changing the shape of the mesh from straight lines to serpentine structures (similar structures are used in wearable electronics). Then, the team transferred the mesh nanoelectronics onto a 2D sheet of stem cells, where the cells covered and interwove with the nanoelectronics via cell-cell attraction forces. As the stem cells began to morph into a 3D structure, the nanoelectronics seamlessly reconfigured themselves along with the cells, resulting in fully-grown 3D organoids with embedded sensors.

The stem cells were then differentiated into cardiomyocytes — heart cells — and the researchers were able to monitor and record the electrophysiological activity for 90 days.

“This method allows us to continuously monitor the developmental process and understand how the dynamics of individual cells start to interact and synchronize during the entire developmental process,” said Liu. “It could be used to turn any organoid into cyborg organoids, including brain and pancreas organoids.”

In addition to helping answer fundamental questions about biology, cyborg organoids could be used to test and monitor patient-specific drug treatments and potentially used for transplantations.

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

Cyborg Organoids: Implantation of Nanoelectronics via Organogenesis for Tissue-Wide Electrophysiology by Qiang Li, Kewang Nan, Paul Le Floch, Zuwan Lin, Hao Sheng, Thomas S. Blum, Jia Liu. Nano Lett.20191985781-5789 DOI: https://doi.org/10.1021/acs.nanolett.9b02512 Publication Date:July 26, 2019 Copyright © 2019 American Chemical Society

This paper is behind a paywall.