Click Hydrogels for Biomedical Applications

Abstract

Hydrogels crosslinked by homopolymerization of single component acrylate/methacrylate terminated polymers (e.g., poly(ethylene glycol) diacrylate, or PEGDA) were once the dominant biomaterials in biomedical applications, including the encapsulation of therapeutic agents and biological molecules. However, accumulating evidence has revealed many disadvantages of homopolymerized hydrogels, including heterogeneity of the crosslinking that adversely impacted the bioactivity of the encapsulated molecules. As such, recent years have witnessed the expansive use of modular click chemistry for the crosslinking of multicomponent hydrogels, typically consisting of two or more functionally distinct macromolecular building blocks. This chapter provides an overview of the crosslinking and applications of multicomponent hydrogels, focusing on those crosslinked by strain-promoted alkyne–azide cycloaddition (SPAAC), Michael-type addition, Diels–Alder (DA) reactions, inverse electron-demand Diels–Alder (iEDDA), thiol–ene polymerizations, and imine/hydrazone/oxime click reactions. This chapter also summarizes information regarding the characteristics, advantages, and limitations of commonly used synthetic (e.g., PEG, poly(acrylate), poly(vinyl alcohol), etc.) and naturally-derived macromers (e.g., gelatin, hyaluronic acid, etc.) for forming multicomponent hydrogels. Finally, an overview is given on the applications of multicomponent hydrogels in drug delivery, biofabrication, and 3D/4D cell culture.