School of Materials Science and Engineering, University of New South Wales, Sydney, NSW 2052, Australia.
Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Biomater Sci. 2021 Jun 15;9(12):4496-4509. doi: 10.1039/d1bm00574j.
The tissue microenvironment contains a complex assortment of multiple cell types, matrices, and vessel structures, which is difficult to reconstruct in vitro. Here, we demonstrate model tumor microenvironments formed through direct writing of vasculature channels and tumor cell aggregates, within a cell-laden microgel matrix. Photocrosslinkable microgels provide control over local and global mechanics, while enabling the integration of virtually any cell type. Direct writing of a Pluronic sacrificial ink into a stromal cell-microgel suspension is used to form vessel structures for endothelialization, followed by printing of melanoma aggregates. Tumor cells migrate into the prototype vessels as a function of spatial location, thereby providing a measure of invasive potential. The integration of perfusable channels with multiple spatially defined cell types provides new avenues for modelling development and disease, with scope for both fundamental research and drug development efforts.
组织微环境包含多种细胞类型、基质和血管结构的复杂混合物,这在体外很难重建。在这里,我们通过直接写入脉管系统通道和肿瘤细胞聚集体,在细胞负载的微凝胶基质中展示了模型肿瘤微环境。光交联微凝胶可控制局部和全局力学,同时可实现几乎任何细胞类型的整合。将泊洛沙姆牺牲墨水直接写入基质细胞-微凝胶悬浮液中,用于形成内皮化的血管结构,然后打印黑色素瘤聚集体。肿瘤细胞作为空间位置的函数迁移到原型血管中,从而提供了侵袭潜力的衡量标准。可灌注通道与多种空间定义的细胞类型的集成提供了用于模拟发育和疾病的新途径,既有基础研究的潜力,也有药物开发工作的潜力。