Current biomedical applications are focused towards solving more challenging problems with sustainable and economic solutions. Drug delivery systems, tissue engineered scaffolds and diagnostic devices are major areas of biomedical systems which require more efficient and benign fabrication and processing. Design of above mentioned systems involves three key components; biomaterial selection, structure and nutrient supply. Various factors such as, biocompatibility, degradation, toxicity, mechanical properties, need to be considered before biomaterial selection for specific application. Polymers are most widely used for biomedical applications due to their ability to tailor properties for specific requirements. Structured patterns are mandatory in most of the biomedical systems such as core-shell structure for drug delivery, porous scaffolds for tissue engineering and microchannels for microfluidics based devices. In the end, these systems demand efficient incorporation of sensitive drug and biomolecules and controlled release. Thus, designing of biomedical systems become a complex process where structure needs to be maintained for a biomaterial throughout the design process. High pressure carbon dioxide (CO2) offers a `green’s benign and inexpensive way for fabrication and impregnation of additives in the biocompatible polymers. CO2 assisted plasticization of polymers enhances diffusion of additives in the polymer matrix. However, interactions among polymer, CO2 and additives are complex and difficult to understand. Density and diffusivity of CO2 can be controlled easily by adjusting temperature and pressure. Hence extent of plasticization of polymer can be controlled. In the present study, biocompatible polymer blends were investigated from biomedical applications perspective. Electrospinning is a versatile process to prepare fibrous scaffolds. This process was applied to different binary and ternary blends to fabricate electrospun scaffolds. There scaffolds were impregnated with additives using high pressure CO2 to study release profiles. Results show electrospun polymer blends interact differently with each process step adopted in this study. Effect of dominant impregnation and release parameters were investigated to control and predict release of additives from complex electrospun scaffolds. The work presented in this dissertation aids in understanding of additive release from electrospun polymer blends with complex behavior. Advisors/Committee Members: Tomasko, David (Advisor).