The fabrication of ordered arrays of self-encapsulated “micro-bubble” material constructs based on the capillary-driven collapse of flexible silk fibroin sheets during propagation of the diffusion front of the encapsulated material is demonstrated. The individual micro-bubbles of different shapes are composed of a sacrificial material encapsulated within the ultrathin silk coating, which covers and seals the inner material during dissolution of supporting layer. The array of microscopic rectangular multi-layer silk sheets on supporting polymer layers can be selectively dissolved along the edges to initiate their self-encapsulation. The resulting micro-bubble morphology, shape, and arrangements can be readily pre-programmed by controlling the geometry of the silk sheets, such as thickness, dimension, and aspect ratio. These micro-bubble constructs can be utilized for encapsulation of various materials as well as nanoparticles in a single or multi compartmental manner. These biocompatible and biodegradable micro-bubble constructs present a promising platform for one-shot spatial and controllable loading and locking material arrays with addressable abilities.