School of Materials Science and Engineering, University of New South Wales, Sydney, NSW, 2052, Australia.
Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, 2052, Australia.
Adv Biosyst. 2020 May;4(5):e2000056. doi: 10.1002/adbi.202000056. Epub 2020 Apr 8.
During cancer progression, a growing tumor encounters variation in the surrounding microenvironment leading to a diverse landscape at the tumor-matrix interface. Topological cues at the interface are believed to influence invasive characteristics; however, most laboratory models involve tumor spheroids that develop a uniform geometry within a homogenous hydrogel. In this communication, a method for templating hydrogels in well-defined 3D architectures is reported. Using melanoma as a model cancer, fabrication of geometrically structured model tumors in a myriad of shapes and sizes is demonstrated. These microtumors can be encapsulated in virtually any polymeric matrix, with demonstrations using poly(ethylene glycol) and gelatin-based hydrogels. Light sheet imaging reveals uniform viability throughout with regions of high curvature at the periphery influencing cellular heterogeneity. These hydrogel encapsulated microtumors can be harvested and implanted in animal models, providing a unique xenograft system where relationships between geometry, progression, and invasion may be systematically studied.
在癌症进展过程中，不断生长的肿瘤会遇到周围微环境的变化，从而导致肿瘤基质界面出现多样化的景观。界面上的拓扑线索被认为会影响侵袭特性；然而，大多数实验室模型涉及的是在同质水凝胶中形成均匀几何形状的肿瘤球体。在本通讯中，报道了一种在明确定义的 3D 结构中模板化水凝胶的方法。使用黑色素瘤作为模型癌症，展示了在各种形状和大小的几何结构模型肿瘤的制造。这些微肿瘤可以封装在几乎任何聚合物基质中，演示中使用了聚乙二醇（PEG）和明胶基水凝胶。光片成像显示整个区域的均匀活力，周边的高曲率区域会影响细胞异质性。这些水凝胶包封的微肿瘤可以被收获并植入动物模型中，提供了一种独特的异种移植物系统，可系统地研究几何形状、进展和侵袭之间的关系。
