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Systems and strategies for promoting tissue growth provide enabling technologies for either enhancing regeneration for diseased or injured tissues, or to investigate abnormal tissue formation such as cancer. Given the complexity inherent in tissues, my laboratory is working towards the concept of "Systems Tissue Engineering", which indicates the dual need i) to develop systems capable of presenting combinations of factors that drive tissue growth, as well as ii) to incorporate systems biology approaches that can identify the appropriate combination of factors. Biomaterial scaffolds represent a central component of many approaches and provide the enabling tools for creating an environment and/or deliver factors that can direct cellular processes toward tissue formation. We have developed scaffolds with the objective of providing factors to stimulate growth and also blocking factors that inhibit regeneration, and will illustrate this approach through our work with islet transplantation in Type 1 Diabetes therapy and scaffolds for the early detection of cancer. The immune response has become a central focus, and will present results for local immunomodulation around the scaffold, as well as the development of nanoparticles for modulating the immune response, in order to induce tolerance in autoimmune disease and allogeneic cell transplantation. The ability to present multiple factors raises the challenge of identifying the combination that will maximally promote tissue formation. Systems biology approaches geared toward identifying the critical factors will also be presented.