(531c) Photo-Mediated Oxime Ligation As a Bioorthogonal Tool for Spatiotemporally-Controlled Hydrogel Formation and Modification

Photoinitiated free radical polymerization has served as a useful tool in hydrogel formation, providing spatiotemporal control over the location and extent of crosslinking, as well as post-gelation functionalization. However, free radicals employed in this polymerization method are prone to non-specific reaction with biomolecules, limiting their potential usage in biological systems and cell encapsulation. Here we present a unique photo-mediated oxime ligation, proceeding through a mechanism independent of propagating free radicals, as an improved tool for hydrogel photopolymerization. Spatial control over the traditional oxime bioorthogonal condensation between alkoxyamines and aldehydes is afforded through alkoxyamine photocaging. Upon cytocompatible UV light exposure, the photocage is cleaved to permit oxime ligation at user-defined regions in time and space. Solutions of four-arm poly(ethylene glycol) macromers separately functionalized with benzaldehyde and photocaged alkoxyamine moieties were found to successfully form hydrogels within minutes following short durations of UV light exposure. Modifying light intensity, exposure time, and aniline catalyst concentration enabled tunable gelation kinetics. Adjusting light intensity and exposure time additionally provided control over final hydrogel moduli. Futhermore, masked light exposure allowed precise control over patterned hydrogel geometry and biochemical functionalization. We expect hydrogel biomaterials formed and modified by photo-mediated oxime ligation will aid in establishing a more-complete understanding of cell-matrix interactions.