Effect of cell culture media on photopolymerizations

Radical polymerization is one of the most widely used methods for the synthesis of polymeric materials for biomedical applications, such as drug delivery, 3D cell culture, and regenerative medicine. Among radical polymerization reactions, thiol-ene click chemistry has shown excellent orthogonality in diverse reaction conditions. However, our preliminary investigations revealed that it fails in cell culture environment. Herein, we investigate the mechanisms by which cell culture media interfere with radical photoreactions. Three different models including free radical linear photopolymerization (N,N-dimethylacrylamide photopolymerization), free radical photohydrogelation (poly(ethylene glycol) diacrylate photohydrogelation), and thiol-ene photohydrogelation (4-arm poly(ethylene glycol)-norbornene thiol-ene photohydrogelation) were investigated. We showed that common cell culture media ingredients can interfere with radical polymerization by two different pathways; namely, radical chain transfer and radical scavenging effects. Thiol-ene photoclick hydrogelation was seriously affected by cell culture media especially under the alkaline conditions of many of them, due to the impact of deprotonation of the thiol reactant. We intend these findings to serve as a reference guide to researchers employing free radical-based molecular synthesis in cell culture settings. The nonbenign impact of media components, pH, and concentration should provide a cue for future studies that aim to prepare well-defined polymeric materials in the presence of cell culture media.