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Nanotechnology for Heart Repair Advances

In a major advance for the application of nanotechnology and tissue engineering to repair hearts suffering severe damage from a heart attack or coronary artery disease, gold nanowires added during the preparation of a tissue patch produced better, more functional heart patches. The advance is described in a PhysOrg.com article by Emily Finn “A heart of gold: Better tissue repair after heart attack (Update)“:

A team of researchers at MIT and Children’s Hospital Boston has built cardiac patches studded with tiny gold wires that could be used to create pieces of tissue whose cells all beat in time, mimicking the dynamics of natural heart muscle. The development could someday help people who have suffered heart attacks.

The study, reported this week in Nature Nanotechnology [abstract], promises to improve on existing cardiac patches, which have difficulty achieving the level of conductivity necessary to ensure a smooth, continuous “beat” throughout a large piece of tissue.

“The heart is an electrically quite sophisticated piece of machinery,” says Daniel Kohane, a professor in the Harvard-MIT Division of Health Sciences and Technology (HST) and senior author of the paper. “It is important that the cells beat together, or the tissue won’t function properly.”

The unique new approach uses gold nanowires scattered among cardiac cells as they’re grown in vitro, a technique that “markedly enhances the performance of the cardiac patch,” Kohane says. The researchers believe the technology may eventually result in implantable patches to replace tissue that’s been damaged in a heart attack. …

A blog article at Children’s Hospital Boston by Nancy Fliesler also describes the work Could nanotechnology improve treatment of heart attack and heart failure?

People who have had a heart attack or have coronary artery disease often sustain damage that weakens their heart. Milder forms of heart failure can be treated with medications, but advanced heart dysfunction requires surgery or heart transplant. …

Tissue-engineered cardiac patches are starting to go into clinical trials for heart patients. They’re made by seeding heart cells onto porous scaffolds that give the tissue shape and organization. But there’s one problem: The heart is an electrically conductive organ, and the scaffolding used for the patches isn’t conductive, so the tissue doesn’t contract as normal heart tissue does.

Tal Dvir and Brian Timko, postdocs in both the Laboratory for Biomaterials and Drug Delivery at Children’s, headed by Daniel Kohane, and the lab of Robert Langer at MIT – came up with an idea: sprinkling tiny gold wires into the patches to enhance their electrical conductivity.

The gold-laced patches … were thicker and their cells better organized. They had ramped-up production of proteins involved in muscle calcium binding and contraction and electrical coupling between cells. And, when stimulated with an electrical current, the cells produced a measurable spike in voltage. …

A short YouTube video shows the dramatic difference in beating between a standard tissue engineered patch and one with gold nanowires.

The bright green color in the video is a dye that shows the propagation of calcium ions through the tissue, tracking how the signals travel between heart cells. With gold nanowires added to the scaffold, the propagation distance of signals increased a thousand fold, from a few hundred micrometers to “many millimeters”—close what is seen in normal hearts where conduction occurs over centimeters.

The article by Emily Finn concludes with an independent assessment from nanowire pioneer and winner of the 2001 Feynman Prize in Nanotechnology-Experimental, Charles Lieber:

“I think other people can take advantage of this idea for other systems: In other muscle cells, other vascular constructs, perhaps even in neural systems, this is a simple way to have a big impact on the collective communication of cells,” Lieber says. “A lot of people are going to be jumping on this.”

The article by Nancy Fliesler also describes a second nanotechnology-based approach to the treatment of heart attack and heart failure:

But he and Dvir also have their eye on another approach, just reported in Nano Letters [abstract]. It uses nanotechnology to create tiny guided missiles that can be injected intravenously, circulate in the blood, then exit at the heart and target tissue damaged by heart attack.

Many current experimental approaches to heart attack involve supplying growth factors, drugs, stem cells and other therapeutic agents to the scarred, dying tissue. Some of these compounds, such as periostin and neuregulin, have been shown in animal models to enhance heart regeneration and improve cardiac function. But the existing delivery approaches are all invasive, involving direct injections into the heart, catheter procedures, or surgical placement of implants that release the necessary factors.

In this work, the researchers demonstrated that nanoparticles called liposomes could be specifically targeted to heart tissue that had suffered an infarction. A molecule that recognizes a protein made in large amounts after heart attacks was attached to the liposome surface, and the liposomes injected into mice with induced heart attacks. They bound only to scarred and not to healthy heart tissue.

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