Abstract

Coronary artery disease, mostly caused by atherosclerosis of coronary arteries, is one of the leading causes of death worldwide (Naghavi et al. , 2015). In the context of coronary artery bypass grafting (CABG), internal mammary arteries, radial arteries and saphenous veins cannot be always used as autologous arterial substitutes (Ishii et al. , 2016) e.g. in patients with multivessel disease (Wipperman et al ., 2009). Synthetic vascular grafts (e.g., Dacron (PET), Teflon (ePTFE)) are an alternative option only to autologous grafts for substitution of vessels with an inner diameter >8 mm (Wippermann et al. , 2009; Weber et al ., 2017). The aim of the project is to develop a Cellulose-based Small Diameter (CSD, 3-4 mm) vascular grafts for coronary artery bypass made of Bacterial nano-Cellulose (BC) reinforced with a Cobalt Chrome mesh. The hypothesis of the study is that CSD vascular grafts are biomechanically suitable to substitute autologous small diameter vessels. In a proof-of-concept study predecessors of these CSD grafts were already used for CABG on pigs. After 4 weeks, angiography showed fully open grafts with no dissection and no narrowing at distal anastomoses. Histology of the explants showed endothelialization from autologous endothelial cells and formation of neointima.The CSD graft is generated in a customized bioreactor providing a temperature- and oxygen-controlled culture environment. BC is synthetized and deposited by Gluconacetobacter around a gas-permeable silicone tube delivering 100% of oxygen. Biological and morphological analyses will be performed and CSD patency will be tested in an in vivo large animal model. It was manufactured up to 20 cm long CSD vascular grafts with a 3-4 mm inner diameter (inner wall thickness 0.5 mm), a circumferential tensile strength of 0.34 ± 0.09 MPa (Force at the breaking point of 1.29 ± 0.28 N), and a burst pressure up to 515.5 ± 94.7 mmHg. Based on an in vitro cytotoxicity test CSD graft resulted not toxic (>70%, n=3). These data indicate the engineered CSD graft as a promising alternative to autologous grafting for coronary artery bypass surgical procedure.

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