Redox-triggerable Luciferin-Bioinspired Hydrogels as Injectable and Cell-encapsulating Matrices

Over the past few decades there has been a great interest in developing smart hydrogels that are stimuli-responsive, due to their ability to respond to variations caused by external stimuli. These materials are exploited for biomedical applications such as biosensors, injectable scaffolds, drug delivery and tissue engineering. Recently, our group reported firefly-inspired hydrogel matrices for 3D cell culture. This platform exhibited certain advantages like rapid gelation rate and tunability of mechanical and biological properties. However, this firstly reported system did not allow for fine control of the gelation onset because the crosslinking reaction started as soon as the two precursors were mixed. Moreover, one of its precursors demonstrated poor storage stability in aqueous solution. These limitations restrict its application as injectable matrices. In this article, we endow the luciferin-inspired hydrogels with redox-triggering capability, to overcome the limitations of the previous system and to widen its application range. We achieve this goal by introducing protected macromers as hydrogel polymeric precursors that can be activated in the presence of a mild reductant, to trigger gel formation in situ with high degree of control. We demonstrate that the regulation of intrinsic (e.g., structure of protecting group, reductant type) and extrinsic (e.g., pH, temperature) parameters of the triggering reaction can be used to modulate key materials properties. This novel upgraded redox-triggerable system enables precise control over gelation onset and kinetics, thus facilitating its utilization as injectable hydrogel without negatively impacting its cytocompatibility. Our findings expand the current toolkit of chemically-based stimuli-responsive hydrogels.