State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016, China.
Biomater Sci. 2018 May 29;6(6):1371-1378. doi: 10.1039/c7bm01153a.
The development of microengineered hydrogels co-cultured with cells in vitro could advance in vivo bio-systems in both structural complexity and functional hierarchy, which holds great promise for applications in regenerative tissues or organs, drug discovery and screening, and bio-sensors or bio-actuators. Traditional hydrogel microfabrication technologies such as ultraviolet (UV) laser or multiphoton laser stereolithography and three-dimensional (3D) printing systems have advanced the development of 3D hydrogel micro-structures but need either expensive and complex equipment, or harsh material selection with limited photoinitiators. Herein, we propose a simple and flexible hydrogel microfabrication method based on a ubiquitous visible-light projection system combined with a custom-designed photosensitive microfluidic chip, to rapidly (typically several to tens of seconds) fabricate various two-dimensional (2D) hydrogel patterns and 3D hydrogel constructs. A theoretical layer-by-layer model that involves continuous polymerizing-delaminating-polymerizing cycles is presented to explain the polymerization and structural formation mechanism of hydrogels. A large area of hydrogel patterns was efficiently fabricated without the usage of costly laser systems or photoinitiators, i.e., a stereoscopic mesh-like hydrogel network with intersecting hydrogel micro-belts was fabricated via a series of dynamic-changing digital light projections. The pores and gaps of the hydrogel network are tunable, which facilitates the supply of nutrients and discharge of waste in the construction of 3D thick bio-models. Cell co-culture experiments showed the effective regulation of cell spreading by hydrogel scaffolds fabricated by the new method presented here. This visible light enabled hydrogel microfabrication method may provide new prospects for designing cell-based units for advanced biomedical studies, e.g., for 3D bio-models or bio-actuators in the future.
体外细胞共培养的微工程水凝胶的发展可以在结构复杂性和功能层次上推进体内生物系统，这在再生组织或器官、药物发现和筛选以及生物传感器或生物执行器的应用方面具有很大的前景。传统的水凝胶微制造技术，如紫外（UV）激光或多光子激光立体光刻和三维（3D）打印系统，已经推进了 3D 水凝胶微结构的发展，但需要昂贵且复杂的设备，或者对光引发剂有限的苛刻材料选择。在此，我们提出了一种基于普遍存在的可见光投影系统结合定制光敏微流控芯片的简单灵活的水凝胶微制造方法，可快速（通常为数秒至数十秒）制造各种二维（2D）水凝胶图案和 3D 水凝胶结构。提出了一个涉及连续聚合-分层-聚合循环的理论层状模型，以解释水凝胶的聚合和结构形成机制。无需使用昂贵的激光系统或光引发剂，即可高效地制造大面积水凝胶图案，即通过一系列动态变化的数字光投影制造具有相交水凝胶微带的立体网格状水凝胶网络。水凝胶网络的孔和间隙是可调的，这有利于在 3D 厚生物模型的构建中提供营养物质的供应和废物的排放。细胞共培养实验表明，通过这里提出的新方法制造的水凝胶支架可以有效地调节细胞的铺展。这种基于可见光的水凝胶微制造方法可能为设计用于先进生物医学研究的基于细胞的单元提供新的前景，例如用于未来的 3D 生物模型或生物执行器。
