posted on 2021-09-17, 12:38authored byMarzieh Monfared, Mitchell D. Nothling, Damia Mawad, Martina H. Stenzel
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.