Varhue Walter B, Rane Aditya, Castellanos-Sanchez Ramon, Peirce Shayn M, Christ George, Swami Nathan S
Electrical and Computer Engineering, University of Virginia, Charlottesville, VA, 22904, USA.
Chemistry, University of Virginia, Charlottesville, VA, 22904, USA.
Organs Chip. 2022 Dec;4. doi: 10.1016/j.ooc.2022.100017. Epub 2022 Jan 15.
The integration of vasculature at physiological scales within 3D cultures of cell-laden hydrogels for the delivery of spatiotemporal mass transport, chemical and mechanical cues, is a stepping-stone towards building tissue models that recapitulate cues. To address this challenge, we present a versatile method to micropattern adjoining hydrogel shells with a perfusable channel or lumen core, for enabling facile integration with fluidic control systems, on one hand, and to cell-laden biomaterial interfaces, on the other hand. This microfluidic imprint lithography methodology utilizes the high tolerance and reversible nature of the bond alignment process to lithographically position multiple layers of imprints within a microfluidic device for sequential filling and patterning of hydrogel lumen structures with single or multiple shells. Through fluidic interfacing of the structures, the ability to deliver physiologically relevant mechanical cues for recapitulating cyclical stretch on the hydrogel shell and shear stress on endothelial cells in the lumen are validated. We envision application of this platform for recapitulation of the bio-functionality and topology of micro-vasculatures, alongside the ability to deliver transport and mechanical cues, as needed for 3D culture to construct tissue models.
在负载细胞的水凝胶三维培养物中整合生理尺度的脉管系统，以实现时空质量传输、化学和机械信号的传递，是构建能够重现这些信号的组织模型的重要一步。为应对这一挑战，我们提出了一种通用方法，用于对相邻的水凝胶壳进行微图案化处理，使其具有可灌注的通道或管腔核心，一方面便于与流体控制系统集成，另一方面便于与负载细胞的生物材料界面集成。这种微流控压印光刻方法利用键对准过程的高耐受性和可逆性，在微流控装置内光刻定位多层印记，以便对具有单个或多个壳的水凝胶管腔结构进行顺序填充和图案化。通过这些结构的流体连接，验证了传递生理相关机械信号以重现水凝胶壳上的周期性拉伸和管腔内内皮细胞上的剪切应力的能力。我们设想将该平台应用于重现微血管的生物功能和拓扑结构，以及根据三维培养构建组织模型的需要传递运输和机械信号的能力。
