The goal of this research is to gain a fundamental understanding of the integrated actuation, embedded sensing, reactive control, and distributed control needs of a cyber-physical, synthetic, distributed sensing, soft and modular tissue (sTISSUE). Realizing this cyber-physical, physiological testbed will enable surgically relevant tasks, procedures, and devices to be much more refined ahead of animal testing, which can be dramatically reduced with such high-fidelity simulators. Furthermore, such simulators could open an entirely new approach to medical resident training that could not only improve surgical performance skills, but also establish a new paradigm in patient-specific surgical practice before the actual procedure. The proposed strategy will also harness the excitement surrounding autonomous systems, robotic control, and embedded sensing, and leverage it with the investigators' infrastructure for education innovation and outreach to provide new, inspirational educational experiences for students. This research program will formulate the techniques required for a synthetic tissue to autonomously sense and react to external stimuli, thereby replicating smooth muscle's sense and actuation capability. In essence, an autonomous tissue will be created that simulates in vivo behavior, while maintaining scalability and modularity. The intellectual merit of this research lies in 1) addressing current shortcomings in embedded sensing and actuation that ensure modularity and distributed control, 2) modeling the dynamics of, and creating global and distributed control strategies that account for, the unconventional in vivo environment requirements, and 3) enabling a paradigm-altering platform that will allow technology developers to both quickly and reliably apply this sTISSUE to numerous applications. More broadly, this research will establish a crucial body of knowledge needed for the design of synthetic tissue materials that integrate sensing, actuation, computation, and control. While the proposed approach includes the goal to transition the fundamental research into a gastrointestinal simulator, numerous other applications in the field of medicine and co-robotics exist. Finally, the proposed research in modularity and scalability design can broadly impact a number of other areas that would benefit from the developed novel methodologies in integrated sensing, actuation, computation and control.