Application of “Click” Chemistry in Biomedical Hydrogels

Abstract

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.

N‐Heterocyclic Imine‐Supported Bimetallic Cu(II) Catalyst for Azide‐Alkyne Cycloaddition: Solvent‐free, Reductant‐free, ppm‐level Catalysis to Access 1,4‐Disubstituted Triazoles

“…The first step entails the elimination of the 2‐amino‐perimidinium ion ( LH 2 + ), which is produced when the basic perimidin‐2‐imine core extracts a proton from a terminal alkyne to initiate the catalytic cycle [1e,21a,32] . Followed by the acetylide, which binds to the active dinuclear copper(I) catalyst ( B ) to yield a copper(I) acetylide ( C ) [7h,33] .…”

Click chemistry for 3D bioprinting

“…Indeed, it is reported that a comparatively low number of hydrogel products, produced from click chemistry are currently being applied in the clinical trials. 300 More work in the area of improving click chemistry and understanding the safety limitations is therefore necessary as such improvement will promote the further development of 3D bioprinting and accelerate application of click chemistry in clinical trials for tissue engineering and regenerative medicine applications.…”

Click-derived multifunctional metal complexes for diverse applications

“…While there are difficulties with the selective and reliable making of molecular connections, the newly emerged fields of Click and bio-orthogonal chemistry have paved the way for the development of new chemical reactions along with their accurate mechanistic insights. 21 The initial Click reactions are highly admired in the history of organic synthesis and reactions include the following: cycloaddition, 22,23 conjugate addition, 24 opening of strained rings, 25 acylation/sulfonylation, 26 a-effect nucleophilic aldehyde capture, etc. The first fundamental breakthrough with the Click chemistry concept happened with the copper-mediated azidealkyne cycloaddition reaction that was further associated with other biocompatible predecessors and made this a hot and more significant field of research.…”

“…The initial Click reactions are highly admired in the history of organic synthesis and reactions include the following: cycloaddition, 22,23 conjugate addition, 24 opening of strained rings, 25 acylation/sulfonylation, 26 α-effect nucleophilic aldehyde capture, etc. The first fundamental breakthrough with the Click chemistry concept happened with the copper-mediated azide–alkyne cycloaddition reaction that was further associated with other biocompatible predecessors and made this a hot and more significant field of research.…”