A smarter ‘bionic’ cardiac patch that doubles as advanced pacemaker/arrhythmia detector

"Cardiac patches might one day simply be delivered by injection" --- Charles Lieber
June 28, 2016

(a) Schematic of the free-standing macroporous nanoelectronic scaffold with nanowire FET (field effect transistor) arrays (red dots). Inset: one nanowire FET. (b) Folded 3D free-standing scaffolds with four layers of individually addressable FET sensors. (c) Schematic of nanoelectronic scaffold/cardiac tissue resulting from the culturing of cardiac cells within the 3D folded scaffold. Inset: the nanoelectronic sensors (blue circles) innervate the 3D cell network. (credit: Xiaochuan Dai at al./Nature Nanotechnology)

Harvard researchers have designed nanoscale electronic scaffolds (support structures) that can be seeded with cardiac cells to produce a new “bionic” cardiac patch (for replacing damaged cardiac tissue with pre-formed tissue patches). It also functions as a more sophisticated pacemaker: In addition to electrically stimulating the heart, the new design can change the pacemaker stimulation frequency and direction of signal propagation.

In addition, because because its electronic components are integrated throughout the tissue (instead of being located on the surface of the skin), it could detect arrhythmia far sooner, and “operate at far lower (safer) voltages than a normal pacemaker, [which] because it’s on the surface, has to use relatively high voltages,” according to Charles Lieber, the Mark Hyman, Jr. Professor of Chemistry and Chair of the Department of Chemistry and Chemical Biology.

Early arrhythmia detection, monitoring responses to cardiac drugs

“Even before a person started to go into large-scale arrhythmia that frequently causes irreversible damage or other heart problems, this could detect the early-stage instabilities and intervene sooner,” he said. “It can also continuously monitor the feedback from the tissue and actively respond.”

The patch might also find use, Lieber said, as a tool to monitor responses to cardiac drugs, or to help pharmaceutical companies screen the effectiveness of drugs under development.

In the long term, Lieber believes, the development of nanoscale tissue scaffolds represents a new paradigm for integrating biology with electronics in a virtually seamless way.

The bionic cardiac patch can also be a unique platform to study the tissue behavior evolving during some developmental processes, such as aging, ischemia, or differentiation of stem cells into mature cardiac cells.

Although the bionic cardiac patch has not yet been implanted in animals, “we are interested in identifying collaborators already investigating cardiac patch implantation to treat myocardial infarction in a rodent model,” he said. “I don’t think it would be difficult to build this into a simpler, easily implantable system.”

Could one day deliver cardiac patch/pacemaker via injection

Using the injectable electronics technology he pioneered last year, Lieber even suggested that similar cardiac patches might one day simply be delivered by injection. “It may actually be that, in the future, this won’t be done with a surgical patch,” he said. “We could simply do a co-injection of cells with the mesh, and it assembles itself inside the body, so it’s less invasive.”

“I think one of the biggest impacts would ultimately be in the area that involves replacement of damaged cardiac tissue with pre-formed tissue patches,” Lieber said. “Rather than simply implanting an engineered patch built on a passive scaffold, our work suggests it will be possible to surgically implant an innervated patch that would now be able to monitor and subtly adjust its performance.”

In the long term, Lieber believes, the development of nanoscale tissue scaffolds represents a new paradigm for integrating biology with electronics in a virtually seamless way.

The study is described in a June 27 paper published in Nature Nanotechnology.

Abstract of Three-dimensional mapping and regulation of action potential propagation in nanoelectronics-innervated tissues

Real-time mapping and manipulation of electrophysiology in three-dimensional (3D) tissues could have important impacts on fundamental scientific and clinical studies, yet realization is hampered by a lack of effective methods. Here we introduce tissue-scaffold-mimicking 3D nanoelectronic arrays consisting of 64 addressable devices with subcellular dimensions and a submillisecond temporal resolution. Real-time extracellular action potential (AP) recordings reveal quantitative maps of AP propagation in 3D cardiac tissues, enable in situtracing of the evolving topology of 3D conducting pathways in developing cardiac tissues and probe the dynamics of AP conduction characteristics in a transient arrhythmia disease model and subsequent tissue self-adaptation. We further demonstrate simultaneous multisite stimulation and mapping to actively manipulate the frequency and direction of AP propagation. These results establish new methodologies for 3D spatiotemporal tissue recording and control, and demonstrate the potential to impact regenerative medicine, pharmacology and electronic therapeutics.