Materials capable of directing cell fate by providing spatially-graded mechanical and biomolecular cues are critically important in the reconstitution of living matter. Herein, we report a multi-component inkjet bioprinting method that allows for spatially varying composition and network properties in cell-instructive glycosaminoglycan (GAG)-based biohybrid and pure poly(ethylene glycol) hydrogels with unprecedented (50 μm) resolution. The principle relies on the covalent crosslinking of different polymeric precursors through a very rapid bio-orthogonal Michael type addition scheme adjusted in ways to occur during the fusion of bio-ink droplets prior to and upon contact with the target. Exemplary data show that chemotactic molecular gradients produced by this approach within printed GAG-gels of defined zonal architecture can effectively direct migratory activity and morphogenesis of embedded human bone-marrow derived mesenchymal stem cells. The introduced methodology is expected to enable a new, holistic level of control over reductionistic tissue and organoid models.

中文翻译：

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多组分水凝胶的高分辨率生物打印。

能够通过提供空间渐变的机械和生物分子线索来指导细胞命运的材料在生命物质的重建中至关重要。本文中，我们报告了一种多组分喷墨生物打印方法，该方法可在基于细胞的糖胺聚糖（GAG）的生物混合和纯聚乙二醇水凝胶中以空前的（50μm）分辨率实现空间变化的组成和网络特性。该原理依赖于通过非常快速的生物正交迈克尔型添加方案的不同聚合物前体的共价交联，该方案以与目标接触之前和之后在生物墨滴融合过程中发生的方式调整。示例性数据显示，在定义的区域结构的印刷GAG凝胶中，通过这种方法产生的趋化分子梯度可以有效指导嵌入式人骨髓来源的间充质干细胞的迁移活性和形态发生。预期引入的方法将能够对还原性组织和类器官模型进行全新的整体控制。