Nontechnical Abstract: Although the cardiac arrhythmia is a serious threat to the public health and afflicts millions of Americans annually, current treatments remain either inadequate or largely palliative. Clinical therapies for cardiac pacing rely exclusively on conventional electronic-only pacemakers that cannot evaluate the patients' full physiology states or change the pacing dynamically. Recent stem-cell technology advance opens the door to biological pacing by engrafting engineered pacemaker tissues for heartbeat restoration, which however faces low success rate in practice.
The proposed hybrid biological-microelectronic pacemaker system combines the advantages of the "biological" and "electrical" pacing and addresses their limitations. First, it solves the limitation of conventional electronic pacemakers by employing engineered cardiac pacemaker cells as "full-spectrum" cell-based sensors that can generate natural cardiac pacing signals and autonomously adjust the pacing rate in response to the patient's real-time physiology conditions, e.g., neurotransmitter release, hormone level shifts, and cardiac drug stimuli. Moreover, the proposed hybrid pacemaker will substantially improve the success rate and lifetime of the biological pacemakers. The living pacemaker cells will be hosted in a bio-compatible package that localizes the cells, enhances viability, and allows their characterizations before deployment. Furthermore, ultra-low-power microelectronics will be included to enable signal conditioning for safe pacing and high-intensity cardiac stimulation.
The proposed hybrid pacemaker will lead to broad societal impacts. It will potentially revolutionize the treatment of arrhythmia-related diseases, substantially increase the clinical success rate, and benefit millions of Americans annually. Moreover, the proposed system can serve as a novel research tool for scientific exploration in fundamental and clinical research on cardiovascular physiology and implantable devices. This project also explores hybrid bioelectronics research frontiers, which are of interest to many scientific communities.
This project offers unique interdisciplinary education opportunities. The PIs will recruit minority undergraduates through existing GT and Emory programs. The research results will be integrated, e.g., as classroom demos, in the bioelectronics and bioengineering courses at GT and Emory. The PIs will particularly emphasize K-12 education outreach for local minority high school students in Atlanta. The research results will be disseminated at publications, conferences, websites, and social media.
The goal of this project is to investigate a novel hybrid biological-microelectronic pacemaker system that harnesses the advantages of both biological pacemaker and electronic pacemaker and explore its use in treating cardiac arrhythmia. The proposed hybrid pacemaker contains an ultra-miniaturized and ultra-low-power implantable hybrid pacing generation module co-operating with a regular electronic pacemaker. The hybrid pacing generation module employs de novo cultured pacemaker cells as a "biological pacing signal synthesizer" to generate natural pacing and respond to the real-time patient physiology conditions and neurohumoral stimuli. These pacemaker cells are encapsulated and hosted on a CMOS integrated circuit (IC) chip that detects the synthesized pacing signals, performs signal conditioning, and sends the pacing signals to the electronic pacemaker by intra-body transmission. The research activities include (1) designing the ultra-low-power CMOS IC for biological pacing signal sensing, conditioning, and transmission, (2) pacemaker cells differentiation and culture on CMOS, (3) designing bio-compatible packaging using hydrogel matrix and 3D-printing, and (4) demonstrations with clinically relevant biological experiments.
This project will explore and establish hybrid biological-microelectronic pacemaker as a disruptive solution for treating cardiac arrhythmia. The research activities and explorations will eventually pave the way toward hybrid bioelectronics systems in the future.
