In vitro endothelialization of small caliber vascular prostheses made of bacterial nanocellulose depending on coating with albumin, fibronectin or heparin

冠状动脉旁路移植术是西方社会最常见的心脏手术。许多患者没有足够的自体移植物材料。替代品，如由塑料纤维组成的合成移植物，并没有产生可接受的结果。这些不良结果主要归因于机械不稳定性和高血栓形成性。我们成功地生产了由细菌纳米纤维素（BNC）组成的创新血管移植物。这些移植物具有与自体血管相当的机械性能。第一个实验显示高闭塞率，主要是由于缺乏内皮化，随后血栓形成。通过在血液中循环的内皮祖细胞来达到血管移植的内皮化被认为是一种有希望提高血管通畅率的方法。最近的研究报道了特异性涂层后BNC内皮化的增加。在我们之前的工作中，我们成功地用白蛋白、纤维连接蛋白和肝素包被BNC。在初步实验中，我们发现包被的BNC移植物上的人微血管内皮细胞扩增增加。本研究的目的是评估涂层在生理条件下对内皮化的影响。因此，我们计划使用我们实验室已经建立的生物反应器。在这个生物反应器中，包被的和未包被的bnc管将被播种于人和羊血管内皮细胞或内皮祖细胞，并在生理流量、压力和温度下灌注细胞培养基。培养3天后，内皮细胞在BNC移植物表面的扩增量将被量化并进行功能表征。我们预计，涂层导致增加内皮化，特别是内皮祖细胞。本研究结果将为未来开发替代移植材料的策略提供重要信息，并将为BNC移植在体内动物实验中的评估提供基础。

Coronary artery bypass grafting is the most frequent heart operation in Western society. Many patients do not have enough autologous graft material. Alternatives, such as synthetic grafts consisting of plastic fiber, did not produce acceptable results. These poor results were mainly attributed to mechanical instability and high thrombogenicity. We managed to produce innovative vascular grafts consisting of bacterial nanocellulose (BNC). These grafts have mechanical properties comparable to autologous vessels. First experiments showed a high occdlusion rate, mainly due to lack of endothelialization followed by thrombosis. Reaching endothelialization of vascular grafts by fishing for endothelial progenitor cells circulating in the blood is considered a promising method to improve patency rates. Recent studies report increased endothelialization of BNC after specific coating. In our previous work, we successfully coated BNC with albumin, fibronectin and heparin. In preliminary experiments we showed increased expansion of human microvascular endothelial cells on the coated BNC grafts. The aim of this study is to evaluate the coating’s impact on endothelialization under physiologic conditions. Therefore, we plan to use a bioreactor that is already established in our laboratory. In this bioreactor, coated and uncoated BNC-tubes will be seeded with human and ovine vascular endothelial cells or endothelial progenitor cells and will be perfused with cell culture media under physiological flow, pressure and temperature. After cultivation for three days, endothelial cell expansion on the BNC graft surface will be quantified and functionally characterized. We expect that the coatings lead to increased endothelialization, especially with endothelial progenitor cells. The results of this study will provide important information for future strategies of developing alternative graft materials and will be the basis for BNC graft assessment in in vivo animal experiments.