There is an acute clinical need for small-diameter vascular grafts as a treatment option for cardiovascular disease. Here, we used an intelligent design system to recreate the natural structure and hemodynamics of small arteries. Nano-fibrous tubular scaffolds were fabricated from blends of polyvinyl alcohol and gelatin with inner helices to allow a near physiological spiral flow profile, using the electrospinning technique. Human coronary artery endothelial cells (ECs) were seeded on the inner surface and their viability, distribution, gene expression of mechanosensitive and adhesion molecules compared to that in conventional scaffolds, under static and flow conditions. We show significant improvement in cell distribution in helical vs. conventional scaffolds (94% ± 9% vs. 82% ± 7.2%; P < 0.05) with improved responsiveness to shear stress and better ability to withhold physiological pressures. Our helical vascular scaffold provides an improved niche for EC growth and may be attractive as a potential small diameter vascular graft.
Doxorubicin-induced cardiomyopathy is a clinically prevalent pathology, occurring as a sequelae following chemotherapy for cancer patients. In particular, the "first dose" effect has been particularly challenging, given the heterogeneous and multifactorial nature of this pathophysiology. Here, we describe the development of a physiologically relevant in vitro model for cardiotoxicity testing, using human cells. Primary cardiomyocytes, endothelial, and smooth muscle cells were tri-cultured in 2D, or within nano-fibrous scaffolds in a 3D environment, under dynamic nutrient flow, using the Quasi Vivo® system. State-ofthe-art sensor chips were used to detect troponin I levels, 2 h after acute exposure to doxorubicin. We demonstrate a significant improvement in cardiomyocyte viability when grown in a 3D tri-culture environment over a 5-day period and a 10-fold reduction in doxorubicin-induced toxicity. Our tri-culture model can be used as a valuable tool for physiologically relevant assessment of drug-induced cardiotoxicity in vitro.
Stroke is mainly caused by a narrowing of the carotid artery from a build-up of plaque. The risk of plaque rupture and subsequent stroke is dependent on plaque composition. Advances in imaging modalities offer a non-invasive means to assess the health of blood vessels and detect damage. However, the current diagnosis fails to identify patients with soft lipid plaque that are more susceptible to fissure, resulting in stroke. The aim of this study was to use waveform analysis to identify plaque composition and the risk of rupture. We have investigated pressure and flow by combining an artificial blood flow circuit with tubing containing different materials, to simulate plaques in a blood vessel. We used fat and bone to model lipid and calcification respectively to determine if the composition of plaques can be identified by arterial waveforms. We demonstrate that the arterial plaque models with different percentages of calcification and fat, results in significantly different arterial waveforms. These findings imply that arterial waveform analysis has the potential for further development to identify the vulnerable plaques prone to rupture. These findings could have implications for improved patient prognosis by speed of detection and a more appropriate treatment strategy.
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