The tissue engineering dichotomy. In tissue engineering, there are two major ways to create 3-dimensional cell aggregates, tissues, or organs, depending on the use of scaffolding materials, such as ECM and ECM-mimetic substances. Scaffold-free techniques often require ultra-low adherent surfaces or methods that would lead to forced-aggregation of cells into spheroids. In contrast, scaffold-based techniques use sold scaffolds (hydrogels, ECM, or synthetic polymers) to guide tissue or organ formation in vitro. As highlighted here, both techniques have pros and cons and the decision often lies with what is more relevant for a specific scenario.