Synthesis and high-throughput processing of polymeric hydrogels for 3D cell culture.

3D cell cultures have drawn a large amount of interest in the scientific community with their ability to closely mimic physiological conditions. Hydrogels have been used extensively in the development of extracellular matrix (ECM) mimics for 3D cell culture. Compounds such as collagen and fibrin are commonly used to synthesize natural ECM mimics; however they suffer from batch-to-batch variation. In this Review we explore the synthesis route of hydrogels; how they can be altered to give different chemical and physical properties; how different biomolecules such as arginylglycylaspartic acid (RGD) or vascular endothelial growth factor (VEGF) can be incorporated to give different biological cues; and how to create concentration gradients with UV light. There will also be emphasis on the types of techniques available in high-throughput processing such as nozzle and droplet-based biofabrication, photoenabled biofabrication, and microfluidics. The combination of these approaches and techniques allow the preparation of hydrogels which are capable of mimicking the ECM.