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Vascular disease – including coronary artery disease, carotid artery disease, and peripheral vascular disease – is a leading cause of morbidity and mortality worldwide. The standard of care for restoring patency or bypassing occluded vessels involves using autologous grafts, typically the saphenous veins or internal mammary arteries. Yet, many patients who need life- or limb-saving procedures have poor outcomes, and a third of patients who need vascular intervention have multivessel disease and therefore lack appropriate vasculature to harvest autologous grafts from. Given the steady increase in the prevalence of vascular disease, there is great need for grafts with the biological and mechanical properties of native vessels that can be used as vascular conduits. In this review, we present an overview of methods that have been employed to generate suitable vascular conduits, focusing on the advances in tissue engineering methods and current three-dimensional (3D) bioprinting methods. Tissue-engineered vascular grafts have been fabricated using a variety of approaches such as using preexisting scaffolds and acellular organic compounds. We also give an extensive overview of the novel use of 3D bioprinting as means of generating new vascular conduits. Different strategies have been employed in bioprinting, and the use of cell-based inks to create de novo structures offers a promising solution to bridge the gap of paucity of optimal donor grafts. Lastly, we provide a glimpse of our work to create scaffold-free, bioreactor-free, 3D bioprinted vessels from a combination of rat vascular smooth muscle cells and fibroblasts that remain patent and retain the tensile and mechanical strength of native vessels.

MCI predicts post-operative delirium and delirium severity, but MCI definition alters these relationships. Cognitive and functional impairment independently predict post-operative delirium and delirium severity.

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Endothelial cells play a central role in the process of inflammation. Their biologic relevance, as well as their accessibility to IV injected therapeutics, make them a strong candidate for treatment with molecularly-targeted nanomedicines. Typically, the properties of targeted nanomedicines are first optimized in vitro in cell culture and then in vivo in rodent models. While cultured cells are readily available for study, results obtained from isolated cells can lack relevance to more complex in vivo environments. On the other hand, the quantitative assays needed to determine the impact of nanoparticle design on targeting efficacy are difficult to perform in animal models. Moreover, results from animal models often translate poorly to human systems. To address the need for an improved testing platform, we developed an isolated vessel perfusion system to enable dynamic and quantitative study of vascular-targeted nanomedicines in readily obtainable human vessels isolated from umbilical cords or placenta. We show that this platform technology enables the evaluation of parameters that are critical to targeting efficacy (including flow rate, selection of targeting molecule, and temperature). Furthermore, biologic replicates can be easily produced by evaluating multiple vessel segments from the same human donor in independent, modular chambers. The chambers can also be adapted to house vessels of a variety of sizes, allowing for the subsequent study of vessel segments in vivo following transplantation into immunodeficient mice. We believe this perfusion system can help to address long-standing issues in endothelial targeted nanomedicines and thereby enable more effective clinical translation. K E Y W O R D S clinical translation, drug delivery systems, endothelial cell targeting, ex vivo perfusion, molecularly targeted therapies, nanoparticle accumulation, nanotechnology