March 22, 2024 | Aysun Degirmenci, Rana Sanyal, and Amitav Sanyal
The article reviews the recent advances in the fabrication of hydrogels using metal-free "click" chemistry, highlighting their applications in biomedical fields. Hydrogels, three-dimensional polymeric networks that can retain high amounts of water, have gained significant attention due to their unique properties such as biocompatibility, biodegradability, and tunable mechanical properties. The advent of "click" chemistry, particularly the copper-catalyzed azide-alkyne cycloaddition (CuAAC), has revolutionized the design of hydrogels by enabling efficient and benign chemical transformations. However, the presence of residual metal impurities in CuAAC reactions can compromise the biological function of the materials.
To address this issue, researchers have shifted towards metal-free "click" transformations, which not only proceed with high reactivity and selectivity under mild conditions but also avoid the formation of toxic byproducts. The review covers various metal-free "click" reactions, including Diels-Alder (DA) and inverse electron demand Diels-Alder (IEDDA) cycloaddition, thiol-ene radical addition, Michael-type thiol-ene reactions, strain-promoted azide-alkyne cycloaddition (SPAAC), Schiff-base reactions, thiol-epoxy, and amine-epoxy "click" reactions.
Key applications of these metal-free "click" reactions in hydrogel fabrication include drug delivery, tissue engineering, and biological sensing. For instance, DA cycloaddition-based hydrogels have been used for self-healing and tissue engineering scaffolds, while IEDDA-based hydrogels have shown promise in cell encapsulation and in situ drug release. Thiol-ene reactions have been employed for enzyme-responsive and biodegradable hydrogels, and thiol-Michael addition reactions have enabled the fabrication of zwitterionic and redox-responsive hydrogels.
The review also discusses the advantages and limitations of each reaction, emphasizing the importance of cytocompatibility, rapid gelation kinetics, and the ability to control the physicochemical properties of the hydrogels. Overall, the use of versatile metal-free "click" reactions is expected to continue revolutionizing the design of functional hydrogels for addressing unmet needs in biomedical sciences.The article reviews the recent advances in the fabrication of hydrogels using metal-free "click" chemistry, highlighting their applications in biomedical fields. Hydrogels, three-dimensional polymeric networks that can retain high amounts of water, have gained significant attention due to their unique properties such as biocompatibility, biodegradability, and tunable mechanical properties. The advent of "click" chemistry, particularly the copper-catalyzed azide-alkyne cycloaddition (CuAAC), has revolutionized the design of hydrogels by enabling efficient and benign chemical transformations. However, the presence of residual metal impurities in CuAAC reactions can compromise the biological function of the materials.
To address this issue, researchers have shifted towards metal-free "click" transformations, which not only proceed with high reactivity and selectivity under mild conditions but also avoid the formation of toxic byproducts. The review covers various metal-free "click" reactions, including Diels-Alder (DA) and inverse electron demand Diels-Alder (IEDDA) cycloaddition, thiol-ene radical addition, Michael-type thiol-ene reactions, strain-promoted azide-alkyne cycloaddition (SPAAC), Schiff-base reactions, thiol-epoxy, and amine-epoxy "click" reactions.
Key applications of these metal-free "click" reactions in hydrogel fabrication include drug delivery, tissue engineering, and biological sensing. For instance, DA cycloaddition-based hydrogels have been used for self-healing and tissue engineering scaffolds, while IEDDA-based hydrogels have shown promise in cell encapsulation and in situ drug release. Thiol-ene reactions have been employed for enzyme-responsive and biodegradable hydrogels, and thiol-Michael addition reactions have enabled the fabrication of zwitterionic and redox-responsive hydrogels.
The review also discusses the advantages and limitations of each reaction, emphasizing the importance of cytocompatibility, rapid gelation kinetics, and the ability to control the physicochemical properties of the hydrogels. Overall, the use of versatile metal-free "click" reactions is expected to continue revolutionizing the design of functional hydrogels for addressing unmet needs in biomedical sciences.