Salehi-Nik Nasim, Banikarimi Seyedeh Parnian, Amoabediny Ghassem, Pouran Behdad, Shokrgozar Mohammad Ali, Zandieh-Doulabi Behrouz, Klein-Nulend Jenneke
School of Chemical Engineering, College of Engineering, University of Tehran, Tehran.
Department of Biomedical Engineering, Research Center for New Technologies in Life Science Engineering, University of Tehran, Tehran, Iran.
Artif Organs. 2017 Jun;41(6):556-567. doi: 10.1111/aor.12759. Epub 2016 Jul 15.
Stability and antithrombotic functionality of endothelial cells on silicone hollow fibers (SiHFs) are critical in the development of biohybrid artificial lungs. Here we aimed to enhance endothelial cell retention and anti-thrombotic function by low (12 dyn/cm , 24 h) fluid shear stress ("flow") preconditioning of endothelial cells seeded on collagen-immobilized SiHFs. The response of endothelial cells without preconditioning (48 h static culture) and with preconditioning (24 h static culture followed by 24 h flow preconditioning) on hollow fibers to high fluid shear stress (30 dyn/cm , 1 h) was assessed in a parallel-plate flow chamber. Finite element (FE) modeling was used to simulate shear stress within the flow chamber. We found that collagen immobilization on hollow fibers using carbodiimide bonds provided sufficient stability to high shear stress. Flow preconditioning for 24 h before treatment with high shear stress for 1 h on collagen-immobilized hollow fibers increased cell retention (1.3-fold). The FE model showed that cell flattening due to flow preconditioning reduced maximum shear stress on cells by 32%. Flow preconditioning prior to exposure to high fluid shear stress enhanced the production of nitric oxide (1.3-fold) and prostaglandin I (1.2-fold). In conclusion, flow preconditioning of endothelial cells on collagen-immobilized SiHFs enhanced cell retention and antithrombotic function, which could significantly improve current biohybrid artificial lungs.
内皮细胞在硅酮中空纤维（SiHFs）上的稳定性和抗血栓形成功能在生物杂交人工肺的发展中至关重要。在此，我们旨在通过对接种在胶原固定化SiHFs上的内皮细胞进行低（12达因/平方厘米，24小时）流体剪切应力（“流动”）预处理，来增强内皮细胞的保留和抗血栓形成功能。在平行平板流动腔中评估了未预处理（48小时静态培养）和经过预处理（24小时静态培养后再进行24小时流动预处理）的中空纤维上的内皮细胞对高流体剪切应力（30达因/平方厘米，1小时）的反应。使用有限元（FE）建模来模拟流动腔内的剪切应力。我们发现，使用碳二亚胺键将胶原固定在中空纤维上可为高剪切应力提供足够的稳定性。在胶原固定化中空纤维上用高剪切应力处理1小时之前进行24小时的流动预处理可使细胞保留率提高（1.3倍）。有限元模型显示，流动预处理导致的细胞扁平化使细胞上的最大剪切应力降低了32%。在暴露于高流体剪切应力之前进行流动预处理可增强一氧化氮（1.3倍）和前列腺素I（1.2倍）的产生。总之，对胶原固定化SiHFs上的内皮细胞进行流动预处理可增强细胞保留和抗血栓形成功能，这可显著改善当前的生物杂交人工肺。
