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According to the World Health Organization, approximately 31% of global deaths resulted from cardiovascular disease (CVD) in 2016. CVD-related mortality is expected to climb steadily in the coming years as the general population grows and more people live to advanced ages.1,2 These trends underscore the valuable role of implantable and wearable cardiovascular electronic devices (CEDs) and sensors to aid in the diagnosis and prevention of adverse outcomes.
How Can CEDs Be Improved?
Considerable advances have been made in the design of such technologies, with resulting benefits to patients in terms of mortality, morbidity, convenience, and quality of life. However, several opportunities for improvement remain, most notably regarding the reliance on battery power and associated issues including finite battery life and limitations in device size and design.
To address these shortcomings, a range of preclinical studies have investigated the use of various types of alternate energy sources to drive self-powered implantable CEDs as well as active sensors for cardiovascular monitoring. As described in a review to be published in January 2021 in Nature Reviews Cardiology, these approaches aim to circumvent the issues associated with the use of batteries by harvesting energy from the human body or environment and converting it into electrical energy that can replace or supplement batteries in cardiovascular devices.2
“These include piezoelectric nanogenerators (PENGs) and triboelectric nanogenerators (TENGs) that can convert biomechanical energy into electrical energy, biofuel cells that can convert chemical energy such as glucose in human blood into electrical energy, pyroelectric nanogenerators that can convert human thermal energy into electrical energy, and solar cells and ultrasonic transducers that can obtain energy from the surrounding environment and convert into electrical energy,” explained review coauthor Zhou Li, PhD, professor at the Beijing Institute of Nanoenergy and Nanosystems at the School of Nanoscience and Technology of the University of Chinese Academy of Sciences in Beijing.
Benefits of PENGs
PENGs can convert kinetic energy from the heart or other organs into electricity. Since the first successful in vivo demonstration of this process in 2010, the technology has been further refined and successfully tested in various animal models.2,3 In a 2015 study using an ultra-flexible piezoelectric device in pigs, the peak-to-peak voltage reached up to 3V, which is similar to the operating voltage of commercial cardiac pacemakers.4
In research published in 2017, an improved PENG model constructed with advanced piezoelectric materials was found to generate an open-circuit voltage (VOC) of 17.8V and a short-circuit current (ISC) of 1.74µA from the heartbeats of pigs. The harvested energy was also sufficient to drive a wireless communication system.5
Advances Gained From TENGs
In the first report of implantable TENG use in cardiovascular medicine in 2014, energy harvested from the breathing of a rat was stored in a capacitor and shown to power a pacemaker prototype to regulate heart rate.6 Since then, significant strides have been made in the development of this technology. In a study published in 2016, an improved model implanted into pigs generated an AC output of 14 V at 5 µA and worked continuously for more than 72 hours.7
Future Directions
In addition, a 2019 investigation8 by Li and colleagues produced a “symbiotic pacemaker” that corrected sinus arrhythmia in pigs, demonstrating the use of “energy harvested in vivo from a large animal to achieve complete pacing functions for the first time, an important breakthrough in the development of self-powered” CEDs, as stated in the current review.2
To learn about these developments and future directions in this area, we spoke further with Dr Li as well as Wenzhuo Wu, PhD, the Ravi and Eleanor Talwar Rising Star Assistant Professor of Industrial Engineering in the College of Engineering at Purdue University in West Lafayette, Indiana.
Cardiology Advisor: What are some of the most notable developments in self-powered cardiovascular devices, and how soon is it anticipated that these devices will be readily available for clinical use?
Dr Li: In the field of self-powered cardiovascular devices, emerging developments consist of 2 primary aspects: self-powered implantable CEDs and wearable active sensors. For the first application, these technologies have been studied for decades and are currently being evaluated in preclinical studies. However, there is still a long way to go – maybe 5 to 10 years – before they may actually be applied in clinical practice, mainly due to the continued improvement of energy efficiency, the long-term evaluation of biosafety, and durability of devices.
For the second application, some researchers have used self-powered wearable active sensors in clinical diagnostic studies investigating their effectiveness in diagnosing cardiovascular diseases such as arrhythmia, atrial septal defect, and coronary heart disease. Compared with the first application, the wearable active sensor can be implemented in the clinic faster, maybe in 1 to 2 years, for use by patients and doctors.
Dr Wu: Some of the most notable recent developments in this area include but are not limited to work from Professors Zhou Li and Zhong Lin Wang’s group at the Beijing Institute of Nanoenergy and Nanosystems.8,9 Their demonstrations are based on the triboelectric process to harvest and convert mechanical signals from the human body into electricity. Other groups, such as Professor John Rogers’ group at Northwestern, also demonstrated a wearable piezoelectric device for cardiovascular monitoring.10
However, these works are mostly based on synthetic polymers or ceramic materials. There are ongoing obstacles in developing efficient triboelectric devices using biocompatible materials. Polyvinyl alcohol (PVA) is one of the most commonly used polymers for biomedical applications and presents opportunities for advancing the development of biocompatible, wearable triboelectric sensors for cardiovascular monitoring.
Cardiology Advisor: Dr Wu, your group published a related study earlier this year. What do your findings add to the advances in this area?
Dr Wu: Our work reports for the first time the holistic engineering and systematic characterization of the impact of molecular and ionic fillers on the triboelectric performance of PVA blends.11 We showed that triboelectric devices created with optimized PVA-gelatin composite films demonstrated stable and robust triboelectricity outputs. “Such wearable devices can detect the imperceptible skin deformation induced by the human pulse and capture the cardiovascular information encoded in the pulse signals with high fidelity,” as reported in our paper.11 “The gained fundamental understanding and demonstrated capabilities enable the rational design and holistic engineering of novel materials for more capable biocompatible triboelectric devices that can continuously monitor vital physiological signals for self‐powered health diagnostics and therapeutics.”
Cardiology Advisor: What are the most immediate or important clinical implications regarding the use of these devices?
Dr Li: For implantable CEDs, although the volume of the CED has been reduced by more than one-half and the service life has almost doubled over the past 2 decades, many patients still require replacement of their CED because of limited battery capacity. As such, physicians are required to balance the patient’s life expectancy and the life of the CED to minimize the need to change the CED and the associated risks of infection and lead complications.
Self-powered implantable CEDs can effectively extend the service life of the devices, which are expected to be implanted once and used for life. This will greatly reduce the risk of secondary operations for patients and the expensive burden on the medical system. At the same time, the self-powered technology will allow the battery part of the CED to be further reduced, thereby reducing the size of the entire device again. This will optimize the operation and benefit both doctors and patients.
For active cardiovascular sensors, certain physiological signals can provide information on cardiovascular health that could help to prevent disease via early diagnosis and treatment. Selfpowered sensors with high sensitivity as well as low power consumption, long life, and longterm stability will make it possible for clinicians to diagnose cardiovascular diseases remotely while freeing patients from the constraints of repeated measurements in clinical settings and enabling uninterrupted, longterm monitoring and treatment.
Dr Wu: Some of the most immediate implications for the use of these devices may be the wearable, noninvasive, continuous, remote monitoring of vital signs and heart disease with minimum power consumption, since these sensors could also harvest their operational power from the human body.
Cardiology Advisor: What are ongoing areas of research and remaining needs in this area?
Dr Li: Selfpowered wearable and implantable CEDs are undergoing continuous evolution. Ongoing research in this area will lead to further improvements in self-powered CEDs to allow for extensive service life, greater miniaturization, improved human conformability, improved sensing capacity, and more. These could ultimately be used for various applications such as postoperative real-time monitoring, chronic disease monitoring and feedback, and in vivo diagnosis and intervention. It is likely that these self-powered sensors and devices will ultimately be adopted as mainstream solutions in cardiovascular medicine.
Dr Wu: Researchers will continue to advance innovation in the material design, manufacturing process, and system engineering to co-optimize the wearability, sensitivity, energy efficiency, biocompatibility, and biodegradability of related sensor devices.
References
1. World Health Organization. Cardiovascular diseases (CVDs). https://www.who.int/en/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds). Accessed on December 3, 2020.
2. Zheng Q, Tang Q, Wang ZL, Li Z. Self-powered cardiovascular electronic devices and systems. Nat Rev Cardiol. 2021;18(1):7-21. doi: 10.1038/s41569-020-0426-4
3. Li Z, Zhu G, Yang R, Wang AC, Wang ZL. Muscle-driven in vivo nanogenerator. Adv Mater. 2010;22(23):2534-2537. doi: 10.1002/adma.200904355
4. Lu B, Chen Y, Ou D, et al. Ultra-flexible piezoelectric devices integrated with heart to harvest the biomechanical energy. Sci Rep. 2015;5:16065. doi: 10.1038/srep16065
5. Kim DH, Shin HJ, Lee H, et al. In vivo self-powered wireless transmission using biocompatible flexible energy harvesters. Adv Funct Mater. 2017;27:1700341. doi: 10.1002.adfm.201700341
6. Zheng Q, Shi B, Fan F, et al. In vivo powering of pacemaker by breathing-driven implanted triboelectric nanogenerator. Adv Mater. 2014;26(33):5851-5856. doi: 10.1002/adma.201402064
7. Zheng Q, Zhang H, Shi B, et al. In vivo self-powered wireless cardiac monitoring via implantable triboelectric nanogenerator. ACS Nano. 2016;10(7):6510-6518. doi: 10.1021/acsnano.6b02693
8. Ouyang H, Liu Z, Li N, et al. Symbiotic cardiac pacemaker. Nat Commun. 2019;10(1):1821. doi: 10.1038/s41467-019-09851-1
9. Ouyang H, Tian J, Sun G, et al. Self-powered pulse sensor for antidiastole of cardiovascular disease. Adv Mater. 2017;29(40). doi: 10.1002/adma.201703456
10. Dagdeviren C, Joe P, Tuzman OL, et al. Recent progress in flexible and stretchable piezoelectric devices for mechanical energy harvesting, sensing and actuation. Extreme Mech Lett. 2016;9(1):269-281. doi: 10.1016.j.eml.2016.05.015
11. Wang R, Mu L, Bao Y, et al. Holistically engineered polymer-polymer and polymer-ion interactions in biocompatible polyvinyl alcohol blends for high-performance triboelectric devices in self-powered wearable cardiovascular monitorings. Adv Mater. 2020;32(32):e2002878. doi: 10.1002/adma.202002878
