Inside-out gelation process to generate hydrogel microcapsules (aka microbeads). Methods of encapsulating biological material in the microbead 3-dimensional hydrogel matrix are described herein. The process generally comprises formation of a mixture of a hydrogel precursor compound, an optional biological material, and a divalent cation. The mixture is then combined with alginate, to generate an alginate shell around droplets of the mixture, followed by gelation of the hydrogel precursor core, and removal of the temporary alginate shell to yield self-sustaining microbeads.