The Texas Heart Institute (THI) and Rice University — both Houston-based, have jointly received a prestigious American Heart Association grant. The three-year, $750,000 grant will support THI and Rice researchers in a study and test of soft, flexible fibers made of carbon nanotubes. The scientists say these fibers’ ability to bridge electrical gaps in tissue is a groundbreaking discovery that offers new hope to millions of people affected by cardiac arrhythmias — that is, any irregularity in the heart’s natural rhythms.
“By virtue of providing us this support, the American Heart Association has offered us a unique opportunity to further validate our initial studies that suggest for the first time cardiac electrical conduction through scarred heart tissue can be normalized in a safe, effective manner,” says Dr. Mehdi Razavi, director of electrophysiology clinical research at THI, and the nanotube research project leader in a release. “Should these more extensive studies confirm our initial findings, a paradigm shift in treatment of sudden cardiac death will be within reach, as for the first time the underlying cause for these events may be corrected on a permanent basis.”
Electrophysiology is the biomedical field involved in study of electric activity in the body, including that of the heart. The mission of the Electrophysiology Clinical Research & Innovations program (ECRI) at Texas Heart Institute is to create and develop an infrastructure for translational and clinical cardiac arrhythmia research and innovation in order to establish THI as a nationally and internationally recognized leader in the field of cardiac arrhythmias.
ECRI is focused on design and implementation of ongoing research projects targeting detection, management, and treatment of cardiac arrhythmias and the development of strategies for community-wide cardiovascular disease education — a program that includes a range of clinical research topics, such as study of the effects of weight loss supplements on heart rhythm; identification of important risk factors for development of specific cardiac rhythm disorders (atrial fibrillation) during and after cardiac surgery; and evaluation of a predictive scoring system and possible interventions to mitigate these risks. EPCI also performs numerous translational and large animal studies to test new drugs, procedures or devices for treatment or prevention of heart rhythm disorders and ECRI investigators have developed the first electrophysiology database for Texas Heart Institute.
Heartbeat is controlled by electrical signals that prompt the vital organ’s tissues to expand and contract. People who develop heart failure can experience formation of scar tissue over time, and these scars conduct little or no electricity, resulting in electrical gaps that consequently exacerbate heart problems.
“These soft, highly conductive fibers may bridge the electric gap in damaged hearts,” explains Dr. Razavi. “They’re like extension cords: they allow us to pick up charge from one side of the scar and deliver it to the other side. Essentially, we’re short-circuiting the short circuit.”
The fibers are being developed at Rice by the cf2 group, led by Professor Matteo Pasquali, whose research is focused on the interaction of flow and liquid micro- and nano-structure. The fibers measure only about a quarter of the diameter of a human hair, and an inch-long piece of the material contains millions of nanotubes. Discovered in the early 1990s, these nanotubes are microscopic cylinders of pure carbon. Originally developed to replace the miles of cables in commercial airplanes as a weight-saving measure, that carbon nanotube fibers invented at Rice University show potential for use in many biomedical applications became quickly apparent as well.
Because carbon nanotube fibers are soft, flexible and extremely tough, they are expected to be far more suitable for biological applications than the metal wires currently used to deliver power to devices like cardiac pacemakers, and their low impedance (resistance to current) allows electricity to move from tissue to bridge and back far better than via metal wires.
“We developed these fibers as high-strength, high-conductivity materials,” Dr. Pasquali observes in a Rice release. “Yet, once we had them in our hand, we realized that they had an unexpected property: They are really soft, much like a thread of silk. Their unique combination of strength, conductivity and softness makes them ideal for interfacing with the electrical function of the human body.”
Because the nanotube fibers provide a two-way connection, they show promise for treating patients with neurological disorders while monitoring the real-time response of neural circuits in areas that control movement, mood and bodily functions, including helping Parkinson’s Disease patients who require brain implants to treat their neurological conditions.The fibers have proven superior to metal electrodes for deep brain stimulation and to read signals from a neuronal network, and may provide the best way to communicate directly with the brain.
A paper published recently in the American Chemical Society journal ACS Nano entitled “Neural Stimulation and Recording with Bidirectional, Soft Carbon Nanotube Fiber Microelectrodes“ (CS Nano, 2015, 9 (4), pp 44654474 DOI: 10.1021/acsnano.5b01060), coauthored by lead investigator Flavia Vitale with Samantha R. Summerson, Behnaam Aazhang, Caleb Kemere, and Matteo Pasquali of the Departments of Chemistry, Material Science & NanoEngineering, and The Smalley Institute for Nanoscale Science & Technology at Rice and the Department of Electrical Engineering and Computer Sciences and Helen Wills Neuroscience Institute at the University of California, Berkeley, notes that development of microelectrodes capable of safely stimulating and recording neural activity is a critical step in the design of many prosthetic devices, brain-machine interfaces, and therapies for neurologic or nervous-system-mediated disorders. The scientists point out that metal electrodes are inadequate media for the degree of miniaturization needed to attain neuronal-scale stimulation and recording because of their relatively poor electrochemical properties, high stiffness, and propensity to fail due to bending fatigue.
In their paper, the investigators demonstrate neural recording and stimulation using carbon nanotube (CNT) fiber electrodes, with in vitro characterization showing that tissue contact impedance of CNT fibers is remarkably lower than that of state-of-the-art metal electrodes, making them suitable for recording single-neuron activity without additional surface treatments. Additionally, in vivo chronic studies in Parkinsonian rodents show that CNT fiber microelectrodes stimulate neurons as effectively as metal electrodes with 10 times larger surface area, while eliciting a significantly reduced inflammatory response. The scientists note that the same CNT fiber microelectrodes can record neural activity for weeks, paving the way for the development of novel multifunctional and dynamic neural interfaces with long-term stability.
The simultaneous arrival in 2012 of Caleb Kemere, a Rice assistant professor who brought expertise in animal models of Parkinson’s disease, and ACS Nano paper lead author Flavia Vitale, a postdoctoral research scientist in Pasquali’s lab with degrees in chemical and biomedical engineering, prompted the investigation.
“The brain is basically the consistency of pudding and doesn’t interact well with stiff metal electrodes,” Dr. Kemere says in a Rice release. “The dream is to have electrodes with the same consistency, and that’s why we’re really excited about these flexible carbon nanotube fibers and their long-term biocompatibility.”
The THI and Rice researchers will continue testing the fibers’ biocompatibility and hope that the first human trials are no more than a few years away. The researchers are delighted that the American Heart Association funding will facilitate continuing their investigative collaboration.
“We’ve been excited from the beginning to learn about each other’s areas and come up with uses for the nanotubes,” comments Dr. Pasquali in a THI release. “We’re determined to find ways to treat rather than manage disease, and we believe this fiber may help us treat all kinds of cardiac arrhythmias and electrical-conduction issues. With this funding, we will be able to continue to push the envelope in the treatment of heart disease.”
The unifying research theme of the cf2 group, led by Dr. Pasquali, is the interaction of flow and liquid micro- and nano-structure. They note that most engineered materials are formed and/or processed in a liquid state and are complex fluids because they possess intrinsic length scales that are well-separated from the macroscopic length scales of the process (usually tens of micrometers to meters) and the nanoscopic length scales of the solvent (usually smaller than one nanometer). For example, in polymer solutions and melts, the intrinsic length scale is the length of the polymer (usually hundreds of nanometers to few micrometers), which is well-separated from the finer length scales (solvent diameter in solution, polymer diameter in melts). The large scale microstructural features relax on timescales that overlap the flow time scales; so the dynamic morphology can differ dramatically from the equilibrium one, and this changing morphology affects the flow and produce what the investigators describe as intriguing nonlinear dynamical phenomena that are not observed in flowing liquids of low-molecular weight.
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