Hydrogel scaffolds find use in the regulated release of biological agents, and as three-dimensional supports for the formation of a tissue matrix. This article addresses the diffusion of moisture from the alginate and chitosan scaffolds under vacuum, and the resulting evolution of pore structure. A fluidic arrangement was used to induce a self-aligned monolayer of bubbles in the aqueous film prior to crosslinking. The regular alignment of bubbles remained unchanged as the film underwent crosslinking and subsequent shrinkage due to the release of moisture. A mathematical model was utilized to derive an effective diffusivity of the scaffold as a function of the moisture content. The gradient in this profile and the limiting value at zero moisture content were analyzed for scaffolds of different thicknesses in the presence or absence of bubbles. The desaturation behavior of the bubble zone, the surface of the scaffold, and the gel matrix were studied. The moisture profile within the scaffold was also simulated using the mathematical model. Copyright © Taylor & Francis Group, LLC.