Collagen Scaffold Arrays for Combinatorial Screening of Biophysical and Biochemical Regulators of Cell Behavior

The native cellular microenvironment is complex, dynamic, and responsible for presenting both biomolecular (e.g., growth factors, cytokines) and biophysical (e.g., mechanical, structural) regulatory signals. While perhaps impossible to fully replicate the complexity of human tissues in engineered biomaterials, there is a specific need for combinatorial biomaterial platforms where combinations of biophysical and biomolecular cues can be rapidly screened. Such tools would enable investigations to identify hierarchies and synergies between multiple signals, and to determine the minimum constellation of cues necessary to induce a desired cellular phenotype. Advances in secretomic, genomic, and functional profiling as well as in systems biology could enable multi-scale analysis of interconnected signaling networks responsible for determining cell fate in response to complex extracellular cues. However, advances in biomaterials technology required to generate adaptable, three-dimensional microenvironments as test platforms to understand cell-material interactions on a similar scale have not yet been realized.