National Engineering Research Center for Tissue Restoration and Reconstruction (NERC-TRR), Guangzhou 510006, People's Republic of China. Department of Biomedical Engineering, School of Material Science and Engineering, South China University of Technology, Guangzhou 510006, People's Republic of China. Key Laboratory of Biomedical Engineering of Guangdong Province, South China University of Technology, Guangzhou 510641, People's Republic of China.
Biofabrication. 2020 Apr 22;12(3):035007. doi: 10.1088/1758-5090/ab7e74.
Inspired by stimuli-tailored dynamic processes that spatiotemporally create structural and functional diversity in biology, a new hierarchical patterning strategy is proposed to induce the emergence of complex multidimensional structures via dynamic sacrificial printing of stimuli-responsive hydrogels. Using thermally responsive gelatin (Gel) and pH-responsive chitosan (Chit) as proof-of-concept materials, we demonstrate that the initially printed sacrificial material (Gel/Chit-H hydrogel with a single gelatin network) can be converted dynamically into non-sacrificial material (Gel/Chit-H-Citr hydrogel with gelatin and an electrostatic citrate-chitosan dual network) under stimulus cues (citrate ions). Complex hierarchical structures and functions can be created by controlling either the printing patterns of citrate ink or the diffusion time of citrate ions into the Gel/Chit-H hydrogel. Specifically, mechanically anisotropic hydrogel film and cell patterning can be achieved via two-dimensional (2D) patterning; complex external and internal 3D structures can be fabricated in stimuli-responsive hydrogel and other hydrogels that are not stimuli-responsive under experimental conditions (also owing to the erasable properties of Gel/Chit-H-Citr hydrogel) via 3D patterning; and an interconnected or segregated fluidic network can be constructed from the same initial 3D grid structure via 4D patterning. Our method is very simple, safe and generally reagentless, and the products/structures are often erasable, compatible and digestible, enabling advanced fabrication technologies (e.g. additive manufacturing) to be applied to a sustainable materials platform.
受生物体内时空构建结构和功能多样性的刺激适应动态过程的启发，提出了一种新的分层图案化策略，通过刺激响应水凝胶的动态牺牲打印来诱导复杂多维结构的出现。使用温度响应明胶（Gel）和 pH 响应壳聚糖（Chit）作为概念验证材料，我们证明最初打印的牺牲材料（具有单个明胶网络的 Gel/Chit-H 水凝胶）可以在刺激下动态转化为非牺牲材料（具有明胶和静电柠檬酸壳聚糖双重网络的 Gel/Chit-H-Citr 水凝胶）提示（柠檬酸根离子）。可以通过控制柠檬酸墨水的打印图案或柠檬酸离子扩散到 Gel/Chit-H 水凝胶中的时间来创建复杂的层次结构和功能。具体而言，通过二维（2D）图案化可以实现各向异性水凝胶膜和细胞图案化；通过 3D 图案化，可以在刺激响应水凝胶和其他在实验条件下不响应刺激的水凝胶中制造复杂的外部和内部 3D 结构（也归因于 Gel/Chit-H-Citr 水凝胶的可擦除特性）；通过 4D 图案化，可以从相同的初始 3D 网格结构构建相互连接或分隔的流体网络。我们的方法非常简单、安全且通常无需试剂，并且产品/结构通常是可擦除的、兼容的和可消化的，使先进的制造技术（例如增材制造）能够应用于可持续材料平台。
