Rapid assessment of migration and proliferation: a novel 3D high-throughput platform for rational and combinatorial...

Designing an ideal biomaterial supportive of multicellular tissue repair is challenging, especially with a poor understanding of the synergy between constituent proteins and growth factors. A brute-force approach, based on screening all possible combinations of proteins and growth factors, is inadequate due to the prohibitively large experimental space coupled with current low-throughput screening techniques. A high-throughput screening platform based on rational and combinatorial strategies for design and testing of proteins and growth factors can significantly impact the discovery of novel tissue-specific biomaterials. Here, we report the development of a flexible high-throughput screening platform, Rapid Assessment of Migration and Proliferation (RAMP), to rapidly investigate cell viability, proliferation, and migration in response to highly miniaturized three-dimensional biomaterial cultures (4-20 μL) with sparingly low cell densities (63-1000 cells per μL for cell arrays; 1 μL of 1000-10,000 cells per μL for migration arrays). The predictions made by RAMP on the efficacy and potency of the biomaterials are in agreement with the predictions made by conventional assays but at a throughput that is at least 100-1000-fold higher. The RAMP assay is therefore a novel approach for the rapid discovery of tissue-specific biomaterials for tissue engineering and regenerative medicine.