Impedimetric Detection and Electromediated Apoptosis of Vascular Smooth Muscle Using Microfabricated Biosensors for Diagnosis and Therapeutic Intervention in Cardiovascular Diseases.

Cardiovascular diseases remain a significant global burden with 1-in-3 of all deaths attributable to the consequences of the disease. The main cause is blocked arteries which often remain undetected. Implantable medical devices (IMDs) such as stents and grafts are often used to reopen vessels but over time these too will re-block. A vascular biosensor is developed that can report on cellularity and is amenable to being mounted on a stent or graft for remote reporting. Moreover, the device is designed to also receive currents that can induce a controlled form of cell death, apoptosis. A combined diagnostic and therapeutic biosensor would be transformational for the treatment of vascular diseases such as atherosclerosis and central line access. In this work, a cell sensing and cell apoptosing system based on the same interdigitated electrodes (IDEs) is developed. It is shown that the device is scalable and that by miniaturizing the IDEs, the detection sensitivity is increased. Apoptosis of vascular smooth muscle cells is monitored using continuous impedance measurements at a frequency of 10 kHz and rates of cell death are tracked using fluorescent dyes and live cell imaging.

Characterising Vascular Cell Monolayers Using Electrochemical Impedance Spectroscopy and a Novel Electroanalytical Plot.

INTRODUCTION: Biological research relies on the culture of mammalian cells, which are prone to changes in phenotype during experiments involving several passages of cells. In regenerative medicine, specifically, there is an increasing need to expand the characterisation landscape for stem cells by identifying novel stable markers. This paper reports on a novel electric cell-substrate impedance sensing-based electroanalytical diagram which can be used for the "electrical characterisation" of cell monolayers consisting of smooth muscle cells, endothelial cells or co-culture. MATERIALS AND METHODS: Interdigitated electrodes were microfabricated using standard cleanroom procedures and integrated into cell chambers. Electrochemical impedance spectroscopy data were acquired for 2 vascular cell types after they formed monolayers on the electrodes. RESULTS AND DISCUSSION: A Mean impedance per unit area vs Mean phase plots provided a reproducible, visually obvious and statistically significant method of characterising cell monolayers. This electroanalytic diagram has never been used in previous papers, but it confirms findings by other research groups using similar approaches that the complex impedance spectra of different cell type are different. Further work is required to determine whether this method could be extended to other cell types, and if this is the case, a library of "signature spectra" could be generated for "electrical characterisation" of cells.

The Future of Cardiovascular Stents: Bioresorbable and Integrated Biosensor Technology.

Cardiovascular disease is the greatest cause of death worldwide. Atherosclerosis is the underlying pathology responsible for two thirds of these deaths. It is the age-dependent process of "furring of the arteries." In many scenarios the disease is caused by poor diet, high blood pressure, and genetic risk factors, and is exacerbated by obesity, diabetes, and sedentary lifestyle. Current pharmacological anti-atherosclerotic modalities still fail to control the disease and improvements in clinical interventions are urgently required. Blocked atherosclerotic arteries are routinely treated in hospitals with an expandable metal stent. However, stented vessels are often silently re-blocked by developing "in-stent restenosis," a wound response, in which the vessel's lumen renarrows by excess proliferation of vascular smooth muscle cells, termed hyperplasia. Herein, the current stent technology and the future of biosensing devices to overcome in-stent restenosis are reviewed. Second, with advances in nanofabrication, new sensing methods and how researchers are investigating ways to integrate biosensors within stents are highlighted. The future of implantable medical devices in the context of the emerging "Internet of Things" and how this will significantly influence future biosensor technology for future generations are also discussed.

Future of Smart Cardiovascular Implants.

Cardiovascular disease remains the leading cause of death in Western society. Recent technological advances have opened the opportunity of developing new and innovative smart stent devices that have advanced electrical properties that can improve diagnosis and even treatment of previously intractable conditions, such as central line access failure, atherosclerosis and reporting on vascular grafts for renal dialysis. Here we review the latest advances in the field of cardiovascular medical implants, providing a broad overview of the application of their use in the context of cardiovascular disease rather than an in-depth analysis of the current state of the art. We cover their powering, communication and the challenges faced in their fabrication. We focus specifically on those devices required to maintain vascular access such as ones used to treat arterial disease, a major source of heart attacks and strokes. We look forward to advances in these technologies in the future and their implementation to improve the human condition.