Meta-adaptive biomaterials: multiscale, spatiotemporal organization and actuation in engineered tissues

Organized cell architecture and dynamic forces are key for (re)creating native-like tissue function (e.g., contractile soft tissues). However, few studies have explored the combined effects of material-guided 3D cell organization with mechanical stimulation. Herein we underscore the importance of converging material-driven guidance of cell organization with stimulus-responsive actuation for multiscale biomaterial design, outlining strategies to engineer such biomaterials. Given the state-of-the-art biomaterials for multiscale spatiotemporally controlled organization and actuation, we propose a synergistic approach ('meta-adaptive biomaterials') that unlocks complexity in engineered biomaterials, harnessing adaptive feedback pathways arising from cell-material interactions. These can be designed similarly to cell-extracellular matrix (ECM) interactions to reinforce user-specified behaviors and yield functionalities that resemble or surpass native tissues, expanding possibilities in tissue engineering, in vitro models, and biohybrid robotics.