Stimulus-induced mechanical compaction of biological polymer networks <i>via</i> smart hydrogel microstructures

The remodeling of the extracellular matrix by mechanical forces plays a crucial role in organizing cellular microenvironments. To study these mechanical perturbations, various methods have been developed to modify the cellular microenvironment and to apply controlled forces. However, most existing approaches rely either on instruments that cannot be integrated into lab-on-chip systems or on small probes with limited spatiotemporal precision. In this work, a lab-on-chip system enables spatially and temporally controlled mechanical perturbations of biological polymer networks. First, thermoresponsive hydrogel microstructures within flow chambers are fabricated and their material composition and photopolymerization parameters are optimized. Second, the expansion of hydrogel microstructures upon a temporally controlled temperature stimulus results in compression of Matrigel and collagen networks. Following compression, Matrigel is plastically deformed, whereas the collagen network relaxes elastically. Finally, the compression of collagen networks is spatially modulated by integrating hydrogel structures responsive to light stimuli and demonstrated to be cell compatible. By mimicking the pushing forces of cells that remodel biological polymer networks, the presented smart hydrogel microstructures provide a versatile system for future studies on extracellular matrix remodeling and the effects of mechanical forces on cellular microenvironments in both physiological and pathological contexts.