Geometrically Structured Microtumors in 3D Hydrogel Matrices

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.