Recent Developments in Thiolated Polymeric Hydrogels for Tissue Engineering Applications

This review focuses on the recent strategy in the preparation of thiolated polymers and fabrication of their hydrogel matrices. The mechanism involved in the synthesis of thiolated polymers and fabrication of thiolated polymer hydrogels is exemplified with suitable schematic representations reported in the recent literature. The 2-iminothiolane namely "Traut's reagent" has been widely used for effectively thiolating the natural polymers such as collagen and gelatin, which contain free amino group in their backbone. The free carboxylic acid group containing polymers such as hyaluronic acid and heparin have been thiolated by using the bifunctional molecules such as cysteamine and L-cysteine via N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide/N-hydroxysuccinimide (EDC/NHS) coupling reaction. The degree of thiolation in the polymer chain has been widely determined by using Ellman's assay method. The thiolated polymer hydrogels are prepared by disulfide bond formation (or) thiol-ene reaction (or) Michael-type addition reaction. The thiolated polymers such as thiolated gelatin are reacted with polyethylene glycol diacrylate for obtaining interpenetrating polymer network hydrogel scaffolds. Several in vitro cell culture experiments indicate that the developed thiolated polymer hydrogels exhibited biocompatibility and cellular mimicking properties. The developed hydrogel scaffolds efficiently support proliferation and differentiation of various cell types. In the present review article, the thiol-functionalized protein-based biopolymers, carbohydrate-based polymers, and some synthetic polymers have been covered with recently published research articles. In addition, the usage of new thiolated nanomaterials as a crosslinking agent for the preparation of three-dimensional tissue-engineered hydrogels is highlighted.