Thiol-Norbornene Photoclick Hydrogels for Tissue Engineering Applications

Thiol-norbornene (thiol-ene) photoclick hydrogels have emerged as a diverse material system for tissue engineering applications. These hydrogels are crosslinked through light-mediated orthogonal reactions between multifunctional norbornene-modified macromers [e.g., poly(ethylene glycol) (PEG), hyaluronic acid, gelatin] and sulfhydryl-containing linkers (e.g., dithiothreitol, PEG-dithiol, biscysteine peptides) with a low concentration of photoinitiator. The gelation of thiol-norbornene hydrogels can be initiated by long-wave UV light or visible light without an additional coinitiator or comonomer. The crosslinking and degradation behaviors of thiol-norbornene hydrogels are controlled through material selections, whereas the biophysical and biochemical properties of the gels are easily and independently tuned because of the orthogonal reactivity between norbornene and the thiol moieties. Uniquely, the crosslinking of step-growth thiol-norbornene hydrogels is not oxygen-inhibited; therefore, gelation is much faster and highly cytocompatible compared with chain-growth polymerized hydrogels with similar gelation conditions. These hydrogels have been prepared as tunable substrates for two-dimensional cell cultures as microgels and bulk gels for affinity-based or protease-sensitive drug delivery, and as scaffolds for three-dimensional cell encapsulation. Reports from different laboratories have demonstrated the broad utility of thiol-norbornene hydrogels in tissue engineering and regenerative medicine applications, including valvular and vascular tissue engineering, liver and pancreas-related tissue engineering, neural regeneration, musculoskeletal (bone and cartilage) tissue regeneration, stem cell culture and differentiation, and cancer cell biology. This article provides an up-to-date overview on thiol-norbornene hydrogel crosslinking and degradation mechanisms, tunable material properties, and the use of thiol-norbornene hydrogels in drug-delivery and tissue engineering applications. (c) 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41563.