Tung Yen-Ting, Chang Cheng-Chung, Ju Jyh-Cherng, Wang Gou-Jen
Program in Tissue Engineering and Regenerative Medicine, National Chung-Hsing University, Taichung, Taiwan.
Graduate Institute of Biomedical Engineering, National Chung Hsing University, Taichung, Taiwan.
Sci Technol Adv Mater. 2017 Mar 1;18(1):163-171. doi: 10.1080/14686996.2016.1278351. eCollection 2017.
The microvascular network is a simple but critical system that is responsible for a range of important biological mechanisms in the bodies of all animals. The ability to generate a functional microvessel not only makes it possible to engineer vital tissue of considerable size but also serves as a platform for biomedical studies. However, most of the current methods for generating microvessel networks use rectangular channels which cannot represent real vessels and have dead zones at their corners, hence hindering the circulation of culture medium. We propose a scaffold-wrapping method which enables fabrication of a customized microvascular network in a more biomimetic way. By integrating microelectromechanical techniques with thermal reflow, we designed and fabricated a microscale hemi-cylindrical photoresist template. A replica mold of polydimethylsiloxane, produced by casting, was then used to generate cylindrical scaffolds with biodegradable poly(lactide-co-glycolide) (PLGA). Human umbilical vein endothelial cells were seeded on both sides of the PLGA scaffold and cultured using a traditional approach. The expression of endothelial cell marker CD31 and intercellular junction vascular endothelial cadherin on the cultured cell demonstrated the potential of generating a microvascular network with a degradable cylindrical scaffold. Our method allows cells to be cultured on a scaffold using a conventional culture approach and monitors cell conditions continuously. We hope our cell-covered scaffold can serve as a framework for building large tissues or can be used as the core of a vascular chip for circulation studies.
微血管网络是一个简单却至关重要的系统,负责所有动物体内一系列重要的生物学机制。生成功能性微血管的能力不仅使构建相当规模的重要组织成为可能,还为生物医学研究提供了一个平台。然而,目前大多数生成微血管网络的方法使用的是矩形通道,这些通道无法代表真实血管,且在角落处存在死区,从而阻碍了培养基的循环。我们提出了一种支架包裹法,能够以更仿生的方式制造定制化的微血管网络。通过将微机电技术与热回流相结合,我们设计并制造了一个微尺度的半圆柱形光刻胶模板。然后,通过浇铸制备的聚二甲基硅氧烷复制模具,用于生成由可生物降解的聚(丙交酯 - 乙交酯)(PLGA)制成的圆柱形支架。将人脐静脉内皮细胞接种在PLGA支架的两侧,并采用传统方法进行培养。培养细胞上内皮细胞标志物CD31和细胞间连接血管内皮钙黏蛋白的表达证明了用可降解圆柱形支架生成微血管网络的潜力。我们的方法允许使用传统培养方法在支架上培养细胞,并持续监测细胞状况。我们希望我们的细胞覆盖支架能够作为构建大型组织的框架,或者用作血管芯片的核心用于循环研究。