Click Chemistry and Material Selection for in Situ Fabrication of Hydrogels in Tissue Engineering Applications

This Review gives a brief introduction to hydrogels formed through click chemistry for applications in tissue engineering. Specifically, we focus on three representative click chemistry mechanisms: Diels-Alder reactions, azide-alkyne cycloaddition, and thiol-ene chemistry. Apart from that, we also discuss photoinitiated chain growth polymerization, which also has fast kinetics. The chemical mechanisms of these reactions, along with their advantages and disadvantages, are presented. These gelation methods are compared and contrasted with other methods of forming hydrogels. Further, we offer an insight on the fabrication of click chemistry hydrogels from a material selection perspective. Commonly used materials from both synthetic and naturally derived polymer families were selected and discussed with their special features and drawbacks in fabricating hydrogels used in tissue engineering applications. At the end, the impact of cross-linking mechanisms and hydrogels properties on the host response is discussed. In conclusion, click reactions are modular and stereospecific. These reactions proceed rapidly with high selectivity, which means they have the potential to be formed in situ with minimal interference on biological processes. In order to achieve optimal hydrogels for tissue engineering applications, it is important to consider different design principles and material fabrication strategies to develop optimal hydrogels for regenerative medicine applications.