Mechanoactive Biomaterials for Cell–Matrix Mechanotransduction

Cells and extracellular matrices (ECMs) form mechanically coupled feedback loops in which cells generate forces, remodel their surroundings, and respond to mechanical information returned by the matrix. Conventional biomaterial models have established how passive matrix properties, including stiffness, viscoelasticity, architecture, and ligand presentation, regulate this feedback, but they provide limited control over the dynamic mechanical inputs transmitted through living tissues. Mechanoactive biomaterials address this limitation by converting external or encoded triggers into mechanical inputs with defined timing, magnitude, frequency, and spatial localization. Here, we compare mechanochemical hydrogels, light-responsive matrices, thermoresponsive systems, and optothermal mechanoactuators according to the material response, the mechanical input experienced by cells, spatial, and temporal control, reversibility, cytocompatibility, quantification, and translational constraints. We discuss how these platforms engage integrin-focal adhesion signaling, mechanosensitive ion channels, cytoskeletal and nuclear mechanotransduction, YAP/TAZ activity, and TGF-β activation. We conclude with design principles for selecting reversible or persistent actuation, matching mechanical parameters to receptor and tissue mechanics, and advancing mechanoactive platforms toward predictive in vitro models.