Spatial Patterning of Molecular Cues and Vascular Cells in Fully Integrated Hydrogel Channels via Interfacial Bioorthogonal Cross-Linking
Spatial Patterning of Molecular Cues and Vascular Cells in Fully Integrated Hydrogel Channels via Interfacial Bioorthogonal Cross-Linking
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DOI：
10.1021/acsami.9b04383
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发表时间：
2019-05-08
影响因子：
9.5
通讯作者：
Jia, Xinqiao
中科院分区：
文献类型：
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作者：
Dicker, Kevin T.;Moore, Axel C.;Jia, Xinqiao
完全集成的水凝胶通道是通过界面生物正交交联，一种扩散控制的方法，用于基于s-四嗪（Tz）和反式环辛烯（TCO）亲二烯体之间的快速生物正交反应来创建和图案化合成基质。将bisTCO交联剂的水溶液注射到四嗪改性的透明质酸（HA-Tz）的储库中，同时将注射器针头拉过储库，产生了机械坚固的交联水凝胶通道。荧光标记物和生化信号通过TCO缀合分子时间依赖性灌注到通道内腔中而在空间上图案化到通道壁中。不同的细胞群体通过HA-Tz储库中细胞的时间改变在空间上封装在通道壁中。界面方法使得血管细胞（包括人腹主动脉内皮细胞、主动脉血管平滑肌细胞和主动脉外膜成纤维细胞）能够空间图案化到水凝胶通道中，所述水凝胶通道具有在人动脉中发现的解剖学顺序中的高活力和适当形态。生物正交平台不依赖于外部触发，代表了功能性和可植入动脉工程的第一步。
Fully integrated hydrogel channels were fabricated via interfacial bioorthogonal cross-linking, a diffusion-controlled method for the creation and patterning of synthetic matrices based on the rapid bioorthogonal reaction between s-tetrazines (Tz) and trans-cyclooctene (TCO) dienophiles. Injecting an aqueous solution of a bisTCO cross-linker into a reservoir of tetrazine-modified hyaluronic acid (HA-Tz), while simultaneously drawing the syringe needle through the reservoir, yielded a cross-linked hydrogel channel that was mechanically robust. Fluorescent tags and biochemical signals were spatially patterned into the channel wall through time-dependent perfusion of TCO-conjugated molecules into the lumen of the channel. Different cell populations were spatially encapsulated in the channel wall via temporal alteration of cells in the HA-Tz reservoir. The interfacial approach enabled the spatial patterning of vascular cells, including human abdominal aorta endothelial cells, aortic vascular smooth muscle cells, and aortic adventitial fibroblasts, into the hydrogel channels with high viability and proper morphology in the anatomical order found in human arteries. The bioorthogonal platform does not rely on external triggers and represents the first step toward the engineering of functional and implantable arteries.