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

由细菌纳米纤维素制成的小口径血管假体的体外内皮化取决于白蛋白、纤连蛋白或肝素的涂层

• 批准号: 421965288
• 负责人: Dr. Max Wacker
• 金额: --
• 依托单位: Klinik für Herz- und Thoraxchirurgie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/421965288?language=en
• 关键词: vitro; endothelialization; small; caliber; vascular

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.

冠状动脉搭桥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。替代方案，如由塑料纤维组成的合成嫁接，没有产生可接受的结果。这些较差的结果主要归因于机械不稳定和高凝血性。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。这些移植物的机械性能可与自体血管相媲美。最初的实验表明血栓闭塞率很高，主要是由于血管内皮细胞缺乏，继而是血栓形成。通过寻找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一种有前途的方法。最近的研究报道，在特定的涂层后，BNC的内皮化程度增加。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覆了BNC。在初步实验中，我们显示了涂层的BNC移植物上的人微血管内皮细胞的扩张增加。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。在该生物反应器中，涂层和未涂层的BNC管分别接种人和绵羊血管内皮细胞或内皮祖细胞，并在生理流量、压力和温度下注入细胞培养液。培养3天后，对BNC移植物表面内皮细胞的扩增情况进行量化和功能鉴定。我们期望涂层能增加内皮化，尤其是内皮祖细胞。本研究的结果将为未来开发替代移植物材料提供重要信息，并将为体内动物实验中评估BNC移植物提供基础。