In this research, hybrid tissue scaffolds are modeled, designed and fabricated to control release kinetics spatially and temporally for improved tissue regeneration. Heterogeneous porous tissue scaffolds with varying characteristics to mediate the release of base material and enclosed biological modifiers are proposed based on tissue engineering requirements. Firstly, a computer-aided biodegradation model is developed to simulate degradation process of micro-patterned polymeric membranes. Next, scaffolds are bio-mimetically designed to control internal porous architecture with varying porosity. A new optimized internal architecture scheme is developed to enhance fluid transport with continuous base material deposition plan. A sample scaffold encapsulated with microspheres is fabricated to explore the natural distribution of microspheres and a stochastic distribution model of biological modifiers is adapted from the image based microsphere distribution model. This study is extended for the development of hybrid scaffolds for spatial control of microspheres and base material to synchronize the release kinetics with tissue regeneration. Finally, a pressure-assisted multi-chamber single nozzle solid freeform fabrication (SFF) technique is utilized to fabricate hybrid scaffolds.