Department of Micro-Nano Mechanical Science and Engineering, Graduate School of Engineering, Nagoya University, 1 Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan.
Department of Micro-Nano Mechanical Science and Engineering, Graduate School of Engineering, Nagoya University, 1 Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan.
J Biotechnol. 2018 Jun 20;276-277:46-53. doi: 10.1016/j.jbiotec.2018.04.003. Epub 2018 Apr 22.
Although there is a great need for suitable vascular replacements in clinical practice, much progress needs to be made toward the development of a fully functional tissue-engineered construct. We propose a fabrication method of engineered tubular tissue for small blood vessels via a layer-by-layer cellular assembly technique using mouse smooth muscle cells, the construction of a poly-(l-lactide-co-ε-caprolactone) (PLCL) scaffold, and integration in a microfluidic perfusion culture system. The cylindrical PLCL scaffold is incised, expanded, and its surface is laminated with the cell layers. The construct confirms into tubular structures due to residual stress imposed by the cylindrical PLCL scaffold. The perfusion culture system allows simulation of static, perfusion (laminar flow), and perfusion with pulsatile pressure (Pulsatile flow) conditions in which mimicking the in vivo environments. The aim of this evaluation was to determine whether fabricated tubular tissue models developed their mechanical properties. The cellular response to hemodynamic stimulus imposed by the dynamic culture system is monitored through expression analysis of fibrillin-1 and fibrillin-2, elastin and smooth muscle myosin heavy chains isoforms transcription factors, which play an important role in tissue elastogenesis. Among the available materials for small blood vessel construction, these cellular hybrid vascular scaffolds hold much potential due to controllability of the mechanical properties of synthetic polymers and biocompatibility of integrated cellular components.
尽管临床实践中非常需要合适的血管替代品，但在开发完全功能性的组织工程构建体方面仍需要取得很大进展。我们提出了一种通过使用小鼠平滑肌细胞的层层细胞组装技术制造用于小血管的工程管状组织的方法，该技术涉及构建聚（L-丙交酯-共-ε-己内酯）（PLCL）支架，并整合到微流控灌注培养系统中。将圆柱形 PLCL 支架切割、扩张，并在其表面层压细胞层。由于圆柱形 PLCL 支架产生的残余应力，构建体可形成管状结构。灌注培养系统允许模拟静态、灌注（层流）和灌注脉动压力（脉动流）条件，从而模拟体内环境。本评估的目的是确定制造的管状组织模型是否发展出了其机械性能。通过对弹性蛋白和平滑肌肌球蛋白重链同工型转录因子的表达分析，监测动态培养系统施加的血流动力刺激对细胞的反应，这些因子在组织弹性发生中起着重要作用。在用于小血管构建的现有材料中，由于合成聚合物的机械性能可控性和整合细胞成分的生物相容性，这些细胞杂交血管支架具有很大的潜力。
