With the recent innovation of flexible microelectronic sensor circuits that can be made from bioresorbable materials, it is now possible to create “electronic stents” to monitor a treated lesion site inside a patient’s artery. A Korean-led team recently published their research on the first device of this kind, showing proof of concept in the American Chemical Society journal ACS Nano.
The engineering and materials sciences team from Kookmin University and Seoul National University created a bioresorbable stent with an embedded set of dissolving microelectronics and performed preliminary testing in an animal study. The stent Dae-Hyeong Kim, Seung Hong Choi, Taeghwan Hyeon and colleagues created not only monitors the revascularized vessel segment for in-stent restenosis, but also can deliver antiproliferative drugs on demand.
Recent future technology sessions at Transcatheter Cardiovascular Therapeutics (TCT) and the American College of Cardiology (ACC) have touched on the possibility of future generation stents having built-in patient monitoring capability. The new research demonstrates the concept is not only feasible, but can be built with current technology, changing the idea of electronic stents from science fiction into the realm of translational medicine. The research offers a glimpse into how the whole concept of stent revacularization might be completely revised in the coming years. The study also introduces the concept of a bioresorbable electronic stent (BES).
New Technology to Monitor Restenosis
Implantable endovascular devices such as bare metal, drug eluting and bioresorbable stents have transformed interventional care by providing continuous structural and mechanical support to blocked arteries. While these devices have a high rate of achieving immediate blood flow restoration, issues with the long-term re-endothelialization and inflammation induced by stents in some patients or anatomy is difficult to diagnose or treat. The researchers set out to use nanomaterial designs and integration strategies to create a bioresorbable electronic stent with drug-infused functionalized nanoparticles.
Electronic Components of the Stent
Researchers collaborated with the Massachusetts-based flexible electronics developer MC10 Inc. The electronics in the stent enable flow sensing and temperature monitoring to measure hemodynamics through the stent and detection of inflammation. The electronics also enable data storage, wireless power and data transmission. The flow sensor measures blood flow, which is stored in the embedded memory module for pattern analysis and diagnosis.
The electronics are also capable of heating up the stent structure, enabling the controlled release of anti-proliferative agents (rapamycin was used in the study) stored in drug-eluting nanoparticles for long-term inflammation suppression. The nanoparticles enable localized antiproliferative drug delivery release on demand for controlled hyperthermia therapy delivery.
The stent in the study was composed of magnesium, which was necessary to use a conductive stent strut for the system that acts as an antenna unit for wireless electronics. Although the magnesium alloy stents have rapid erosion problems, the researchers believe the degradation time can be prolonged by multistacked encapsulation layers.
The electronics are completely bioresorbable and are incorporated into stacks of active electronics and therapeutic nanoparticles used to coat the magnesium alloy stent. The electronic components consist of bioresorbable magnesium, magnesium oxide, zinc, zinc oxide and polylactic acid (PLA) and bioinert manganese materials. PLA is what is used for all current commercially available bioresorbable stents in Europe.
Nanoparticle Drug Delivery System
The therapeutic nanoparticles are incorporated in the PLA layers of the stent. The coating also helps control the dissolution rate of the magnesium stent struts and active electronic components.
Inorganic ceria (Cerium oxide) nanoparticles were used in the study as therapeutic platforms because of their high surface-to-volume ratio, ability to scavenge reactive oxygen species (ROS) and photoactivation properties. Researchers said the catalytic ROS ceria nanoparticles scavenge ROS generated in the perfusion by percutaneous coronary intervention (PCI), helping reduce inflammation that can cause in-stent thrombosis. The nanoparticle includes a gold nanorod core and a mesoporous silica shell design to control the drug loading and its release photothermally. The hyperthermia, which is regulated via feedback temperature sensing, controls localized drug delivery as well, researchers explained in the study.
In addition to the protection against ROS and inflammation, the multifunctional therapeutic nanoparticles are responsive to external optical stimuli to enable controlled drug release. Since drug-loaded nanoparticles are bound by PLA chains, the release rate is slow, and thereby continuous/controlled nanoparticle-based therapy over an extended period of time is possible, researchers said. To achieve this form of actuation on the BES, researchers designed nanoparticles with a near-infrared (NIR) laser responsive gold nanorod core and drug-loadable mesoporous silica shell.
“By modulating the NIR laser power, we controlled the dosage of drug released from the BES,” researchers wrote in the study. “Although guiding the NIR beam through the optical fiber to endovascular locations for photothermal therapies is still challenging, the drug delivery induced by guided-NIR was successfully demonstrated through in-vivo animal experiments. Furthermore, the radio frequency (RF) magnetic field can induce heat on the stent for accelerated drug diffusion.”
Researchers concluded the modeling and material analysis validate the mechanical robustness of the active components and the thermal stability of hyperthermia-induced therapies using nanoparticles as a basis for future optimization of stent design. In-vitro, ex-vivo and in-vivo studies demonstrate the biocompatibility and multifunctional electronic and therapeutic utilities of the proposed biointegrated system. The study conclusion added that further work will focus on the integration of wireless power and data communication in bioresorbable formats.
“In-vivo and ex-vivo animal experiments as well as in-vitro cell studies demonstrate the previously unrecognized potential for bioresorbable electronic implants coupled with bioinert therapeutic nanoparticles in the endovascular system,” researchers concluded in the study.
Researchers and collaboraters in the study included the Center for Nanoparticle Research, Institute for Basic Science, Seoul; School of Chemical and Biological Engineering and Institute of Chemical Processes, Seoul National University, Seoul; MC10 Inc.; School of Electrical and Computer Engineering and INMC, Seoul National University; Department of Radiology, Seoul National University College of Medicine; Center for Mechanics of Solids, Structures and Materials, Department of Aerospace Engineering and Engineering Mechanics, Texas Materials Institute, University of Texas at Austin; Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, China; School of Advanced Materials Engineering, Kookmin University, Seoul; and the Department of Materials Science and Engineering and Inter-university Semiconductor Research Center, Seoul National University.
1. Donghee Son, Jongha Lee, Dong Jun Lee,et al. “Bioresorbable Electronic Stent Integrated with Therapeutic Nanoparticles for Endovascular Diseases.” American Chemical Society (ACS) Nano. DOI: 10.1021/acsnano.5b00651. Publication Date (Web): April 23, 2015