Bioorthogonal Click Degradable Mechanically Strong Hydrogels

Abstract Hydrogels with high mechanical strength at equilibrium swelling are crucial for load-bearing applications. However, despite significant progress in the development of strong hydrogels, their in vivo applications remain limited by the need for invasive surgical removal after use. Bioorthogonal click chemistry is introduced in this work as a biocompatible strategy for the post-use on-demand degradation of mechanically strong hydrogels. We designed a strong chemically degradable single-network hydrogel by crosslinking poly(2-isopropenyl-2-oxazoline) with 2-(diphenylphosphino)terephthalic acid as a bifunctional crosslinker that facilitates Staudinger–Bertozzi ligation-induced hydrogel degradation with azide compounds while also enhancing the hydrogel mechanical properties through hydrophobic interactions to enhance network robustness. This hydrogel exhibits excellent biocompatibility and ultra-high compressive strength (16.1 MPa), which can be readily tuned by adjusting the crosslinking density. The strong hydrogel undergoes controlled degradation via bioorthogonal click chemistry upon contact with an aqueous azido-glucose solution while avoiding the formation of toxic byproducts. The in vivo degradation behavior of the hydrogel is demonstrated in a mouse model that was also used to confirm the hydrogel biocompatibility during in vivo implantation and degradation. In summary, this study established a new strategy for the design of strong hydrogels with on-demand controllable degradation through click chemistry-induced breaking of crosslinks.