The quest to develop state-of-the-art hydrogels for bone tissue engineering has accompanied substantial innovation and significant progression in the field of bioactive hydrogels. Still, there is scope for advancement in this cell-friendly and biocompatible scaffold system. The crosslinking approaches used for hydrogel synthesis plays a decisive role in guiding and regulating the mechanical stability, network framework, macroscopic architect, immunological behaviors, and cellular responses. Until recently, enzyme-based crosslinking strategies were considered as the pinnacle in designing efficient hybrid hydrogel systems. A variety of enzymes have been explored for manufacturing hydrogels while taking the advantage of the biocompatible nature, specificity, ability to produce nontoxic by products and high efficiency of enzymes. The current review focuses on the utility of different enzymes as crosslinking agents for hydrogel formation with their application in bone tissue engineering. The field of enzyme crosslinked hydrogel synthesis is rapidly maturing with a lot of opportunities to be explored in bone tissue engineering. Enzyme-based in situ and externally crosslinked hydrogels for bone regeneration is an attractive field, and with innovation in using engineered enzymes this field will continue to flourish with clinical orientation.
Keywords: biomaterials; bone tissue engineering; crosslinking; enzyme; hydrogels; polymers.