Cardiovascular diseases (CVD) remain one of the leading causes of mortality worldwide. Despite recent advances in diagnosis and interventions, there is still a crucial need for new multifaceted therapeutics that can address the complicated pathophysiological mechanisms driving CVD. Extracellular vesicles (EVs) are nanovesicles that are secreted by all types of cells to transport molecular cargo and regulate intracellular communication. EVs represent a growing field of nanotheranostics that can be leveraged as diagnostic biomarkers for the early detection of CVD and as targeted drug delivery vesicles to promote cardiovascular repair and recovery. Though a promising tool for CVD therapy, the clinical application of EVs is limited by the inherent challenges in EV isolation, standardization, and delivery. Hence, this review will present the therapeutic potential of EVs and introduce bioengineering strategies that augment their natural functions in CVD.

Implantable vascular devices are widely used in clinical treatments for various vascular diseases. However, current approved clinical implantable vascular devices generally have high failure rates primarily due to their surface lacking inherent functional endothelium. Here, inspired by the pathological mechanisms of vascular device failure and physiological functions of native endothelium, we developed a new generation of bioactive parylene (poly(p-xylylene))-based conformal coating to address these challenges of the vascular devices. This coating used a polyethylene glycol (PEG) linker to introduce an endothelial progenitor cell (EPC) specific binding ligand LXW7 (cGRGDdvc) onto the vascular devices for preventing platelet adhesion and selectively capturing endogenous EPCs. Also, we confirmed the long-term stability and function of this coating in human serum. Using two vascular disease-related large animal models, a porcine carotid artery interposition model and a porcine carotid artery-jugular vein arteriovenous graft model, we demonstrated that this coating enabled rapid generation of self-renewable "living" endothelium on the blood contacting surface of the expanded polytetrafluoroethylene (ePTFE) grafts after implantation. We expect this easy-to-apply conformal coating will present a promising avenue to engineer surface properties of "off-the-shelf" implantable vascular devices for long-lasting performance in the clinical settings.