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Cholesterol plaque in blood vessel

Prosthetic Vascular Graft Technology Improvement Research

Endothelial Cells and Peripheral Arterial Disease

Endothelial cells comprise the innermost later of blood vessels, forming a barrier between the circulating blood and the tissues of the body. In particular, endothelial cells participate in extensive crosstalk with the blood to maintain vascular homeostasis.

Endothelial cells are particularly important in cardiovascular diseases like atherosclerosis. Atherosclerosis occurs when plaque (composed of fat, cholesterol, and other molecules) builds up on artery walls, increasing the risk of blood clots and artery blockage. Atherosclerosis also contributes to peripheral arterial disease, which is the narrowing of arteries that do not supply the brain or heart. Importantly, peripheral arterial disease can lead to complications including tissue death or stroke. Peripheral arterial disease is often treated with prosthetic grafts; however, as discussed below, use of grafts constructed using the currently available technology is associated with negative side effects.

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Recent Research Using Lifeline® Aortic Endothelial Cells in Biomaterials Research

One of the challenges of using prosthetic vascular grafts for the treatment of peripheral arterial disease is the proliferation of endothelial cells around the anastomosis, also called anastomotic neointimal hyperplasia. Therefore, continued effective treatment of peripheral arterial disease relies on the improvement of prosthetic vascular graft technology. To approach this challenge, Huynh and colleagues (opens in new window) set out to construct a bioactive graft system, composed of polyethylene terephthalate (PET) and cryogel technology, called hybrid grafts. They tested their hybrid grafts with PET in three forms: electrospun (ePET), knitted (kPET), or woven (wPET). All hybrid grafts were coated with an alginate cryogel.

The authors first assessed the microstructure of the hybrid grafts using scanning electron microscopy and confirmed the porous structure of the cryogel was intact after 8 weeks. Next, evaluating the physical properties of the hybrid grafts, they found that the hybrid grafts had increased shape recovery, decreased swelling ratio, but no differences in stiffness compared with the cryogel alone.

To test the bioactivity of the hybrid grafts, the group incubated the grafts with Lifeline® human aortic endothelial cells (HAoECs) and confirmed that the cells adhered to and incorporated into the hybrid grafts after one day. Additionally, viability assays demonstrated that HAoECs adhered and proliferated on all hybrid grafts, although at a slower rate than on the cryogel alone.

The authors then tested the ability of HAoECs growing on hybrid grafts to be transduced with adeno-associated virus (AAV). Following transduction of an AAV-green fluorescent protein (GFP) construct, GFP expression was observed by Day 7. Finally, the group tested the ability of hybrid grafts containing heparin (an anti-thrombotic agent) to release the heparin over time. Indeed, they observed that the three heparin-containing hybrid grafts released heparin over the course of seven days.

Together, the data presented in this study demonstrate that PET is a graft material that can be used to develop bioactive prosthetic graft systems with anti-thrombotic properties.

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