Alginate modification via click chemistry for biomedical applications

Alginate biopolymers are characterized by favorable properties, of biocompatibility, degradability, and nontoxicity. However, the poor stability properties of alginate have limited its suitability for diverse applications. Recently, click chemistry has generated significant research interest due to its high reaction efficiency, high selectivity for a single product, harmless byproducts, and processing simplicity. Alginate modified using click chemistry enables the production of alginate derivatives with enhanced physical and chemical properties. Herein, we review the employment of click chemistry in the development of alginate-based materials or systems. Various click chemistries were highlighted, including azide and alkyne cycloaddition (e.g. Copper-(I)-catalyzed azide-alkyne cycloaddition (CuAAC), Strain-promoted alkyne-azide cycloaddition (SPAAC)), Diels-Alder reaction (Inverse electron demand Diels-Alder (IEDDA) cycloaddition, Tetrazine-norbornene Diels-Alder reactions), Thiolene/yne addition (Free-radical thiol-ene addition click reactions, Thiol-Michael addition click reactions, Thiolyne addition click reaction), Oxime based click reactions, and other click reactions. Alginate functionalized with click chemistry and its properties were also discussed. The present study shows that click chemistry may be employed in modifying the mechanical strength, biochemical/biological properties of alginate-based materials. Finally, the applications of alginate-based materials in wound dressing, drug delivery, protein delivery, tissue regeneration, and 3D bioprinting were described and the future perspectives of alginates modified with click chemistry, are subsequently presented. This review provides new insights for readers to design structures and expand applications of alginate using click chemistry reactions in a detailed and more rational manner.