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材料。替代品，如由塑料纤维组成的合成移植物，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。我们设法生产出由细菌纳米纤维素（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，随后是血栓形成。通过捕获血液中循环的内皮祖细胞来实现血管移植物的内皮化被认为是提高通畅率的有前途的方法。最近的研究报告，特定涂层后BNC的内皮化增加。在我们以前的工作中，我们成功地用白蛋白、纤连蛋白和肝素包被了BNC。在初步的实验中，我们发现在包被的BNC移植物上人微血管内皮细胞的扩增增加。本研究的目的是评价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。在该生物反应器中，将用人和绵羊血管内皮细胞或内皮祖细胞接种涂层和未涂层BNC管，并在生理流量、压力和温度下灌注细胞培养基。培养三天后，将对BNC移植物表面上的内皮细胞扩增进行定量和功能表征。我们预期涂层导致内皮化增加，尤其是内皮祖细胞。本研究的结果将为未来开发替代移植材料的策略提供重要信息，并将成为在体内动物实验中评估BNC移植物的基础。

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.