| Popis: |
Cardiovascular diseases (CVD) is one of the main causes of death worldwide. Coronary heart disease (CHD) and strokes are the highest contributors to CVD deaths (46 % and 26 % respectively) in the UK. The condition which leads to CHD is Coronary artery disease (CAD). The main cause of CAD is coronary atherosclerosis, which involves an inflammatory response of the artery wall to chronic multifactorial injury, which then results into formation of atherosclerotic plaques. One of the main treatment strategies for CAD is Percutaneous Coronary Intervention (PCI). PCI is a procedure during which a balloon mounted catheter with an unexpanded stent is inserted into a peripheral artery and threaded up to the site of stenosis in the coronary artery of the heart to reopen the vessel. PCI usually involves stenting with a Bare Metal Stent (BMS) or Drug Eluting Stent (DES). The 9-month revascularisation rate is 12.32 % with BMS, and this rate has significantly decreased to 4.34 % with early generation DES. The latest generation of DES is associated with revascularisation rates of 2.91 %. Detection of this vascular hyperplasia is a common limitation of these devices which can be found across a number of vascular pathologies. In this project, we developed a new type of biosensor for detecting the changes associated with these blockages that could be mounted on these implantable medical devices. Our design and development led to a comprehensive characterisation of both the sensor and its cell interactions. Proof of concept experiments were performed that legitimised the concept of a smart self-reporting device, as a solution to remote detection of In-stent Restenosis (ISR). The proposed smart stent would have both diagnostic and therapeutic capabilities. Preliminary tests showed that the devices were minimally susceptible to changes in volume and conductivity of culture medium, during baseline measurements. Sensors of different dimensions were fabricated with the best version 16 times smaller but with 4.35 times higher sensitivity in cell detection compared to baseline. Our sensor could also distinguish between different cell types. Indeed the sensor coverage could be remotely monitored intermittently (at 24 h intervals) or continuously (at 15 min intervals) or on demand. Continuous monitoring allowed the gradual changes in cell phenotype to be monitored including cell adherence, proliferation and death which was then correlated with live cell sensor imaging. We found our sensors could be used for both cell detection and therapeutic intervention. As the fabricated biosensors are intended to be integrated onto a future smart stent, this would be implanted in vivo and would be subjected to blood flow. Therefore it was important to test the devices under flow conditions. Our data show that, when incorporated into microfluidic flow chambers, the sensors could exquisitely detect cell adherence under flow and static conditions. Moreover they were also suitable for monitoring the gradual migration and proliferation of vascular cells within a microfluidic channel. Future development of these proof-of-concept biosensors is critical for future commercialisation of this important novel device, which hopefully will provide a new class of diagnostic and therapeutic vascular devices. |
