Application of “Click” Chemistry in Biomedical Hydrogels

[Image: see text] Since “click” chemistry was first reported in 2001, it has remained a popular research topic in the field of chemistry due to its high yield without byproducts, fast reaction rate, simple reaction, and biocompatibility. It has achieved good applications in various fields, especially for the preparation of hydrogels. The development of biomedicine presents new challenges and opportunities for hydrogels, and “click” chemistry provides a library of chemical tools for the preparation of various innovative hydrogels, including cell culture, 3D bioprinting, and drug release. This article summarizes several common “click” reactions, including copper-catalyzed azide–alkyne cycloaddition reactions, strain-promoted azide–alkyne cycloaddition (SPAAC) reaction, thiol–ene reaction, the Diels–Alder reaction, and the inverse electron demand Diels–Alder (IEDDA) reaction. We introduce the “click” reaction in the nucleic acid field to expand the concept of “click” chemistry. This article focuses on the application of “click” chemistry for preparing various types of biomedical hydrogels and highlights the advantages of “click” reactions for cross-linking to obtain hydrogels. This review also discusses applications of “click” chemistry outside the field of hydrogels, such as drug synthesis, targeted delivery, and surface modification, hydrogels have great application potential in these fields in the future and hopefully inspire other applications of hydrogels.