<p>Additive manufacturing (AM) of hydrogels has gained increasing interest across various fields. Drop-on-demand (DOD) printing (also known as inkjet printing) shows the great potential to construct 3D hydrogels with spatially controlled properties and compositions. However, a limited mechanistic understanding of the behavior of printed polymer drops makes it challenging to design and optimize DOD printing protocols for a wide variety of hydrogels. Here, we have demonstrated an extensive and in-depth study from the theoretical and experimental research of drop-wise structure to the development of functional materials by DOD printing of polymer inks. First, computational and experimental studies are performed to establish a mechanism of the water-matrix interaction within printed polymer drops. The results ultimately enabled a dimensionless parameter that characterizes water transport during the dehydration process of printed polymer drops. Next, as particles are suspended in polymer inks to add functionality, this dimensionless parameter was further extended to characterize particle movement and distribution patterns in the printed particle-laden hydrogels. By correlating the intra-drop particle distribution to the similarity parameter, a scaling law is confirmed to guide ink formulation and printing protocol that enables advanced materials with spatially digitized functionality (i.e., digital hydrogels). Finally, cells that serve as active particles are embedded in the hydrogels to mimic the native tissues. A "digital cell printing" method based on DOD printing of "two colors" cell-laden (i.e., cancer cells and CAFs) polymer inks is developed to rapidly (< 1 day) create 3D tumor models with tumor-stroma interface (i.e., tumoroids) and high cell density (~108 cells/cm3) that closely recapitulate the tumor microenvironment in vivo. Overall, DOD printing of particulate-laden polymer inks showed the great potential to construct 3D functional hydrogels with spatially controlled properties and compositions.</p>