Mechanomedicine Platforms: Engineering Hydrogel Mechanics for Next-Generation Vaccines

Traditional vaccines face significant limitations, including rapid antigen degradation, weak immune responses, limited durability, and complex logistics requiring cold-chain storage. Mechanomedicine, which leverages engineered hydrogels with precisely tunable mechanical properties, offers innovative solutions by creating stable antigen reservoirs that prolong antigen release and enhance immune activation. Emerging research has highlighted key mechanotransduction pathways, including integrins, Piezo1 channels, and yes-associated protein/transcriptional co-activator with PDZ-binding motif (YAP/TAZ) signaling, through which immune cells respond to mechanical cues from the hydrogel matrix. By systematically adjusting hydrogel stiffness, viscoelasticity, porosity, and degradation kinetics, researchers can optimize antigen presentation, amplify germinal center responses, and simplify delivery routes, significantly improving vaccine thermostability and patient compliance. Integrating biophysical insights, materials science, and immunology, mechanomedicine may support vaccines that deliver potent, durable immunity, greater accessibility, and improved equity. This review highlights the interdisciplinary potential of mechanically engineered hydrogels as a platform to improve global vaccination strategies.