Bioinspired Microstructure Platform for Modular Cell-Laden Microgel Fabrication

Cell-laden microgels have attracted increasing interest in various biomedical fields, as living building blocks to construct spatially organized multicellular structures or complex tissue features (e.g., cell spheroids and aligned cells/fibers). Although numerous approaches have been developed to tailor cell-laden microgels, there is still an unmet need for modular, versatile, convenient, and high-throughput methods. In this study, as inspired by the phenomena of water droplet manipulation from natural microstructures, a novel platform is developed to manipulate microscale hydrogel droplets and fabricate modular cell-laden microgels. First, taking antenna-like trichome as a template, catcher-like bioinspired microstructures are fabricated and hydrogel droplets are manipulated modularly in a versatile, convenient, and high-throughput manner, which is compatible with various types of hydrogels (e.g., photo-cross-linking, thermal-cross-linking, and ion-cross-linking). It is demonstrated that this platform can manipulate cell-laden microgels as modular units, such as two or more cell-laden microgels on one single catcher-like structure and different structures on one single chip. The authors also demonstrate the application of this platform on constructing complex tissue features like myocardial fibrosis tissue models to study cardiac fibrosis. The developed platform will be a powerful tool for engineering various in vitro tissue models for widespread biomedical applications.