Brief Introduction and Various Crosslinking Approaches

Physically crosslinked hydrogels have gained popularity in recent years and the interest was driven by the fact that the necessity of utilizing crosslinking agents during its preparation is eliminated. Hydrogels are referred to as “chemical” or “permanent” if they are covalently crosslinked, and it differs to physically crosslinked hydrogels in which the hydrogen bonds are replaced by more stable and stronger covalent bonds. The use of enzymes to create covalently crosslinked hydrogels can resolve several drawbacks and limitations created by some of the more commonly used crosslinking approaches such as the insufficient mechanical stability and strength associated with physically crosslinked hydrogels or the potential of cytotoxicity in photoinitiator-based hydrogels. “Click” chemistry is a high-yield, highly selective, rapid, and spontaneous chemical reaction between two molecules under mild conditions and its utilization enables hydrogels to be crosslinked via several approaches with physical and chemical properties customizable to suit the intended application. Copper-free “click” chemistry has emerged as a useful technique for synthesizing hydrogels intended to be used in regenerative medicine and tissue engineering and it offers numerous functionalities without the use of any toxic catalysts or produce any toxic end-product after gel formation.