Hydrogels are an exciting platform technology for solutions in many high impact areas, including bioadhesive tissue sealants to cease internal hemorrhaging and injectable biomaterials for tissue reinforcement. Precision engineering of hydrogels is essential to developing high performance materials such as these, which also need to be adapted to a variety of practical processing conditions. Our efforts are focused on developing well-defined macromolecular systems that can be used to study the fundamentals physics of gels at the nanoscale, develop new mechanisms of responsive gel reinforcement and toughening, and engineer bioactive materials for controlled cell delivery and tissue integration. Control over gel structure allows us to investigate the structure-property relationships that are critical determinants of gel performance, including the role of network topology on the mechanics of chemical and physical gels, as well as the role of nanostructure morphology on the mechanics of supramolecular gels. In addition, we are developing hierarchically structured gels that can capture the complex viscoelastic behavior of natural tissues. To accomplish these objectives, we employ a broad range of traditional and biological approaches to polymer synthesis, allowing us to engineer model systems with architectural control and sequence specificity, as well as to develop scalable systems for direct applications. By understanding and controlling new mechanisms for energy storage and dissipation in advanced hydrogels, we aim to develop novel materials with applications as tissue adhesives, hemostats, reinforcing tissue fillers, cell delivery vehicles, and ballistic gels.