Tunable biomaterials that mimic selected features of the extracellular matrix (ECM), such
as its stiffness, protein composition, and dimensionality, are increasingly popular for studying how cells
sense and respond to ECM cues. In the field, there exists a significant trade-off for how complex and how
well these biomaterials represent the in vivo microenvironment, versus how easy they are to make and
how adaptable they are to automated fabrication techniques. To address this need to integrate more
complex biomaterials design with high-throughput screening approaches, we present several methods to
fabricate synthetic biomaterials in 96-well plates and demonstrate that they can be adapted to semiautomated
liquid ... More
Tunable biomaterials that mimic selected features of the extracellular matrix (ECM), such
as its stiffness, protein composition, and dimensionality, are increasingly popular for studying how cells
sense and respond to ECM cues. In the field, there exists a significant trade-off for how complex and how
well these biomaterials represent the in vivo microenvironment, versus how easy they are to make and
how adaptable they are to automated fabrication techniques. To address this need to integrate more
complex biomaterials design with high-throughput screening approaches, we present several methods to
fabricate synthetic biomaterials in 96-well plates and demonstrate that they can be adapted to semiautomated
liquid handling robotics. These platforms include 1) glass bottom plates with covalently
attached ECM proteins, and 2) hydrogels with tunable stiffness and protein composition with either cells
seeded on the surface, or 3) laden within the three-dimensional hydrogel matrix. This study includes
proof-of-concept results demonstrating control over breast cancer cell line phenotypes via these ECM
cues in a semi-automated fashion. We foresee the use of these methods as a mechanism to bridge the
gap between high-throughput cell-matrix screening and engineered ECM-mimicking biomaterials.
