Shape-changing hydrogel surfaces trigger rapid release of patterned tissue modules

The formation and assembly of diverse tissue building blocks is considered a promising bottom-up approach for the construction of complex three-dimensional tissues. Patterned shape-changing materials were investigated as an innovative method to form and harvest free-standing tissue modules with preserved spatial organization and cell–cell connections. Arrays of micro-scale surface-attached hydrogels made of a thermoresponsive polymer were used as cell culture supports to fabricate tissue modules of defined geometric shape. Upon stimulation, these hydrogels swelled anisotropically, resulting in significant expansion of the culture surface and subsequent expulsion of the intact tissue modules. By varying the network crosslink density, the surface strain was modulated and a strain threshold for tissue module release was identified. This mechanical mechanism for rapid tissue module harvest was found to require inter- and intra-cellular tension. These results suggest that the cell–matrix adhesions are disrupted by the incompatibility of surface expansion with tissue module cohesion and stiffness, thus providing a novel method of forming and harvesting tissue building blocks by a mechanism independent of the thermal stimulus that induces the biomaterial shape change.