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Tissue Engineering Part B: Reviews In Vivo Applications of Electrospun Tissue-Engineered Vascular Grafts: A Review (doi: 10.1089/ten.TEB.2014.0123) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.

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In Vivo Applications of Electrospun Tissue-Engineered Vascular Grafts: A Review Kevin A. Rocco, MS1,a, Mark W. Maxfield, MD2,b, Cameron Best3,c, Ethan W. Dean2,d, and Christopher K. Breuer, MD3,e* 1

Department of Biomedical Engineering, Yale University 10 Amistad St. New Haven CT, 06519 USA

2

Department of Surgery, Yale School of Medicine 10 Amistad St. New Haven CT, 06519 USA

3

Nationwide Children’s Hospital Research Institute, 575 Children’s Crossroads, Columbus OH, 43215 USA

a

[email protected], T: 860-301-8638 F: 614-355-5726

b

[email protected], T: 201-314-4425 F: 614-355-5726

c

[email protected], T: 614-355-5754 F: 614-355-5726

d

[email protected], T: 706-247-4038 F: 614-355-5726

e

[email protected] T: 614-355-5754 F: 614-355-5726

*Corresponding Author: Christopher K Breuer, MD 700 Children’s Drive – WB4151 Columbus, Ohio 43205

Keywords: Tissue Engineering, Vascular Grafts, TEVG, Electrospinning, Scaffolds, Biomaterials

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Tissue Engineering Part B: Reviews In Vivo Applications of Electrospun Tissue-Engineered Vascular Grafts: A Review (doi: 10.1089/ten.TEB.2014.0123) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.

2 I. Abstract There is great clinical demand for synthetic vascular grafts with improved long-term efficacy. The ideal vascular conduit is easily implanted, nonthrombogenic, biocompatible, resists aneurysmal dilatation, and ultimately degrades or is assimilated as the patient remodels the graft into tissue resembling native vessel. The field of vascular tissue engineering offers an opportunity to design the ideal synthetic graft, and researchers have evaluated a variety of methods and materials for use in graft construction. Electrospinning is one method that has received considerable attention within tissue engineering for constructing so-called tissue scaffolds. Tissue scaffolds are temporary, porous structures, commonly composed of bioresorbable polymers that promote native tissue ingrowth and have degradation kinetics compatible with a patient’s rate of extracellular matrix production in order to successfully transition from synthetic conduit into neovessel. In this review, we summarize the history of tissue-engineered vascular grafts (TEVG), focusing on scaffolds generated by the electrospinning process, and discuss in vivo applications. We review the materials commonly employed in this approach and the preliminary results following implantation in animal models in order to gauge clinical viability of the electrospinning process for TEVG construction. Scientists have studied electrospinning technology for decades, but only recently has it been orthotopically evaluated in animal models as TEVG. Advantages of electrospun TEVG include ease of construction, favorable cellular interactions, control of scaffold features such as fiber diameter and pore size, and the ability to choose from a variety of polymers possessing a range of mechanical and chemical properties and degradation kinetics. Given its advantages, electrospinning technology merits investigation for use in TEVG, but an emphasis on long-term in vivo evaluation is required before its role in clinical vascular tissue engineering can be realized.

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Tissue Engineering Part B: Reviews In Vivo Applications of Electrospun Tissue-Engineered Vascular Grafts: A Review (doi: 10.1089/ten.TEB.2014.0123) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.

3 II. Introduction There is an enormous need for vascular grafts worldwide. Much of the disease that requires vascular bypass is related to atherosclerosis, a vascular disease that leads to luminal narrowing, decreased flow, and distal tissue ischemia. Atherosclerosis of the coronary arteries is a particularly lethal form of atherosclerosis and is a leading cause of death in the United States, accounting for 1 of every 6 deaths in 2006. [1] Atherosclerosis of the major vessels—including the aorta, iliac, femoral, and popliteal arteries—is also a significant source of morbidity and mortality. Atherosclerotic lesions are treated with either angioplasty or surgical bypass, the latter of which requires a vascular graft to divert flow around the lesion. Given its prevalence, coronary artery disease is an expensive medical problem, with over $40 billion spent annually on procedures related to it. [1] Numerous other diseases and conditions require vascular grafts. Arteriovenous grafts are used for dialysis access in patients with end stage renal disease (ESRD). There were approximately 400,000 Americans on dialysis in 2009, a number which will increase in the future as the number of individuals with ESRD due to diabetic nephropathy is increasing at a greater rate than that of available donor kidneys. [2] Vascular grafts are also employed in pediatric heart operations, where congenital heart defects often require operative reconstruction of the vessels into and out of the left and right ventricles. Mesenteric ischemia due to atherosclerosis of the mesenteric arteries is an additional disease in which surgical bypass can relieve symptoms. For most vascular bypass procedures, autologous vascular tissue is the surgeon’s graft of choice. Autologous tissue is advantageous in that it has a living, non-thrombogenic endothelium, is biocompatible, and has favorable surgical handling characteristics. Examples of harvested vessels for vascular grafting include internal mammary artery, radial artery, and greater saphenous vein, and all are commonly used for coronary artery bypass surgery (CABG). Unfortunately, many patients lack suitable donor tissue either due to inherent disease or harvest during previous operations. In these instances, surgeons must employ synthetic vascular conduits like expanded polytetrafluoroethylene (ePTFE i.e. Gortex) or polyethylene terephthalate (PET i.e. Dacron®). [3] 3

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Tissue Engineering Part B: Reviews In Vivo Applications of Electrospun Tissue-Engineered Vascular Grafts: A Review (doi: 10.1089/ten.TEB.2014.0123) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.

4 These two materials have been used clinically since 1956 and have been validated as successful conduits for large caliber arteries in which high flow and low resistance leads to low rates of thrombosis and excellent rates of long-term patency. [4] Despite the ready availability and clinical efficacy of Dacron and Gortex grafts in specific applications, there is much room for improvement. The results of synthetic vascular grafts for bypass of small diameter (

In vivo applications of electrospun tissue-engineered vascular grafts: a review.

There is great clinical demand for synthetic vascular grafts with improved long-term efficacy. The ideal vascular conduit is easily implanted, nonthro...
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