3D high throughput assays for combinatorial screening of biomaterials for tissue regeneration

Tissue engineered strategies suffer from a lack of complexity, which manifests itself as unsatisfactory functional recovery in clinical applications. Better understanding of cell response to complex combinations of matrix proteins and growth factors mediating regeneration is necessary for increased biomaterial performance. A high throughput 3D multiplex assay has been designed for evaluating cell behavior in response to differential composite biomaterials. Specifically, Schwann cell (SC) and neuronal viability, death, and morphology were measured in response to varying collagen (COL) hydrogel concentration (1-3 mg/mL) and Matrigel™ (MAT) concentration (0-100% v/v). SCs were sensitive to differences in MAT and relatively insensitive to COL differences within this range, whereas neurons were sensitive to changes in both MAT and COL concentration. This strategy is capable of rapidly identifying large differences in cell behavior within combinatorial biomaterials, demonstrating its utility for narrowing large experimental libraries to optimal multifunctional composite materials.