Superparamagnetic Iron-Oxide nanoparticles (SPIO) are used as magnetic resonance imaging (MRI) contrast agents in clinical and research applications, effectively increasing the imaging sensitivity of MRI. Current clinical MRI applications utilizing SPIO are limited to liver and gastrointestinal imaging, but further bioengineering will expand the capabilities of SPIO enhanced MRI. This thesis presents different methods of bioengineering SPIO contrast agents for MRI applications. In particular, chemical methods are developed to manipulate contrast agent size via aggregation, modify contrast agent surface encapsulation, and biofunctionalize contrast agents for new applications. Contrast agent sizes from 15 nm to 100 nm are synthesized by nanoparticle aggregation, yielding a new method to incrementally size contrast agent sizing for specific applications. Mono- and Diethoxy silane surface chemistries are applied to SPIO to develop quasi-monolayer biocompatible contrast agent surface encapsulations. Finally, biofunctionalization enables two new applications of SPIO contrast agents, as a new MRI-based method to detect inflammation in vivo, and as a bifunctional MRI contrast agent and nanoparticle antigen delivery system.