Engbers-Buijtenhuijs Paula, Buttafoco Laura, Poot Andre A, Dijkstra Piet J, de Vos Rob A I, Sterk Lotus M Th, Geelkerken Rob H, Vermes Istvan, Feijen Jan
Department of Polymer Chemistry and Biomaterials, Faculty of Science and Technology and Institute for Biomedical Technology (BMTI), University of Twente, Enschede, P.O. Box 217, 7500 AE, The Netherlands.
Biomaterials. 2006 Apr;27(11):2390-7. doi: 10.1016/j.biomaterials.2005.10.016. Epub 2005 Dec 15.
In this study, the development is described of a tissue-engineered construct mimicking the structure of a natural blood vessel. Smooth muscle cells (SMC) were cultured under pulsatile flow conditions in porous tubular scaffolds composed of crosslinked type I insoluble collagen and insoluble elastin. Under these dynamic culture conditions, average wall shear rate, systolic and diastolic pressures and pressure wave-forms comparable to conditions in the human carotid artery were obtained. Culturing of SMC in tubular scaffolds under dynamic conditions resulted in enhanced tissue formation compared to static conditions. Higher SMC numbers, a more homogeneous distribution of SMC throughout the scaffolds and higher collagen mRNA expression levels were found when cells were cultured under dynamic compared to static conditions. mRNA expression levels of markers of proliferation and apoptosis showed that the higher cell numbers in the scaffolds cultured under dynamic conditions can be explained by increased cell proliferation but not by decreased apoptosis. Glucose consumption and lactate formation by the cells showed that cell metabolism was more aerobic under dynamic compared to static conditions. Lining of the dynamically cultured constructs with a luminal monolayer of endothelial cells might result in vessels suitable for in vivo applications.
在本研究中,描述了一种模仿天然血管结构的组织工程构建体的开发。平滑肌细胞(SMC)在由交联I型不溶性胶原蛋白和不溶性弹性蛋白组成的多孔管状支架中,在脉动流条件下进行培养。在这些动态培养条件下,获得了与人类颈动脉条件相当的平均壁剪切率、收缩压和舒张压以及压力波形。与静态条件相比,在动态条件下于管状支架中培养SMC导致组织形成增强。与静态条件下培养的细胞相比,动态培养的细胞时,发现SMC数量更多、SMC在整个支架中的分布更均匀且胶原蛋白mRNA表达水平更高。增殖和凋亡标志物的mRNA表达水平表明,动态条件下培养的支架中较高的细胞数量可通过细胞增殖增加来解释,而非细胞凋亡减少。细胞的葡萄糖消耗和乳酸生成表明,与静态条件相比,动态条件下细胞代谢更具需氧性。用内皮细胞的管腔单层对动态培养的构建体进行内衬可能会产生适合体内应用的血管。