Hybrid Microtissues as Programmable Living Materials: Engineering Function through Integrated Material Compartments

Hybrid microtissues are scaffold-free multicellular living architectures containing retained and spatially definable material compartments that extend, enhance, spatially organize, or externally control biological function from within. Unlike particle-containing spheroids or simple mixtures of cells and particles, hybrid microtissues require stable multicellular organization, retained material integration, and experimentally demonstrated functional translation at the cellular, microtissue, or host-tissue level. In this viewpoint, we define the concept and its boundaries, position hybrid microtissues as a functionally defined subclass of programmable living materials, and classify material compartments as instructive, actuatable, reporting, or microenvironment regulating. We evaluate representative evidence for these functions and identify material identity, localization, dose, cellular association, and persistence as key design variables. Finally, we highlight unresolved challenges in causal validation, spatial control, reproducibility, and translation.