Thermosetting resins are materials that undergo crosslinking by forming interchain linkages to create robust 3D networks that impart creep, thermomechanical, and solvent resistance. These materials are critical for a number of high-performance applications, such as aerospace and automotives, and biomedical crosslinked hydrogels. Thermosetting materials can be cured chemically or thermally, or by using ultraviolet (UV) light or electron beams. However, these methods are not always possible, accessible, and they can be harsh to embedded cells. Taking inspiration from natural materials such as fibronectin, a protein that contains hidden or cryptic sites that become exposed under tension, this dissertation first presents a new class of synthetic force-responsive materials that exhibit force-responsive behavior by exposing cryptic sites and forming new crosslinks. Long pendant poly(ethylene glycol) (PEG) chains along the polymer backbone create a significant steric barrier and prevent reactive moieties from spontaneously crosslinking, which is overcome by mechanical force. In this dissertation, I extended this approach to densely grafted comb polymers with reactive side chains, which resulted in highly crosslinked comb copolymers with minimal intramolecular crosslinking. Finally, I harnessed xanthogen disulfides to produce telechelic acrylic polymers and hydrogels responsive to visible light. Overall, I successfully designed and produced methods of easily implementing mechanosensitivity in synthetic polymers, strategies for producing high molecular weight crosslinkable resins, and fast techniques for synthesizing biocompatible gels. Importantly, the design principles laid out in this work provide a blueprint for developing next-generation stimuli responsive materials.