Autologous
vessels, such as the internal mammary artery (IMA) or the saphenous vein are
commonly used for small-diameter grafts 1, 2. However, there can
be a lack of availability in small-diameter grafts, due to vascular disease,
amputation or previous harvest 3. Therefore,
synthetic vascular grafts have been used as an alternative to autologous vessels
with satisfactory long-term results in vessels with an inner diameter above 8 mm
4, 5. Unfortunately,
despite the clinical success of large diameter vascular grafts, synthetic
grafts in small-diameter vessels (<6 mm) are rarely used, due to poor patency rates, which limit their application in coronary and peripheral vascular bypass graft procedures 2, 6-9.   Hence, non-thrombogenic materials with good biocompatibility and favorable mechanical characteristics are required, that mimic the compliance and strength of the native vessels 8, 10. Several attempts have been made to test the application of tissue-engineered vascular grafts (TEVG) for the replacement of small-diameter vessels 3, 6, 11-16.   One promising concept is the use of the hydrogel bacterial nanocellulose (BNC) designed in tubular shape. As reviewed in 2011 BNC is an emerging biomaterial with great potential as a biological implant, wound and burn dressing material, and scaffolds for tissue regeneration 17. The water-holding ability up to 99% is the most probable reason why BNC implants do not elicit any foreign body reaction. The structure of BNC materials can be engineered by controlling the biological fabrication using Gluconacetobacter strains 17, 18. BNC tubes are formed around a cylindrical guide bar using a patented layer-by-layer technique 19, 20. Correspondingly, the inner layer of the BNC tube is characterized by the surface of this guide bar. Depending on the surface of the guide bar, the inner layer of the BNC tube has a smoother or rougher inner surface. BNC grafts offer mechanical stability and maintain structural integrity, while providing a porous architecture that supports cellular ingrowth 10, 21-23. Moreover, they resemble the mechanical characteristics of native arteries and show good blood compatibility in vitro and in vivo 3, 8, 14, 24, 25.   BNC scaffolds demonstrated promising results in vitro, as well as in the first large animal study of our group 14. In our "proof of concept study" we replaced the carotid artery of 10 sheep for a period of three month to gain further insights into the in vivo performance of first-generation BNC tubes as small diameter grafts 3. Our investigations showed immigrated vascular smooth muscle cells and a luminal endothelium-like monolayer, which stained positive for von-Willebrand-factor (vWF) without any obvious signs of an overt inflammatory reaction. However, the overall patency rate of first-generation tubes was only 50 % after three month. Graft occlusion appeared to be caused by thrombus formation next to the proximal anastomoses, due to a mismatch concerning the wall thickness of the native vessel in comparison to the first-generation BNC tubes.   To advance our concept, we now used modified second-generation tubes with different surface properties and diminished wall thickness in order to generate a smoother inner surface with reduced thrombogenic potential and a more porous outer zone allowing easier cell immigration. The present study aimed to assess these new second-generation BNC tubes with regard to (1) mechanical characteristics (bursting strength and suture retention strength), (2) in vivo performance and biocompatibility and (3) thrombogenic potential and patency over a period up to 9 months.       METHODS Experimental Design The experimental design consists of two evaluation phases. In the first step, the thinner second-generation BNC tubes were implanted in 18 sheep. 9 sheep received aspirin (100 mg, q.d., Bayer Vital GmbH, Leverkusen, Germany) and clopidogrel (75 mg, q.d., ABZ Pharma GmbH, Ulm, Germany), whereas the remaining 9 sheep served as an untreated control group. The investigation period was nine months to evaluate long-term patency.