Photodegradable Hydrogels Formed by Thiol-Norbornene Photopolymerization of Poly(ethylene glycol)-Norbornene-Carboxylate

Orthogonally cross-linked thiol-norbornene hydrogels are a versatile biomaterial platform for tissue engineering applications. Multiarm poly-(ethylene glycol)-norbornene (PEGNB) is the original macromer for thiol-norbornene hydrogel cross-linking, but a lengthy reaction and the use of nauseous 5-norbornene-2-carboxylic acid burdened its synthesis. Recently, a PEGNB variant, PEG-amide-norbornene-carboxylate (PEGaNB_CA), was prepared by reacting PEG-amine with odorless carbic anhydride (CA) under ambient aqueous conditions. In this work, we employed a microwave reactor for the aqueous synthesis of PEGaNB_CA, significantly reducing the synthesis time from 48 h to ∼22.5 min while increasing the degree of norbornene substitution to over 93%. Furthermore, we discovered that the thioether bonds formed after photo-cross-linking of PEGaNB_CA with a thiol-bearing cross-linker were hydrolytically stable but susceptible to radical-mediated photodegradation. Macromer functionality and formulation were evaluated to achieve full photodegradation of the photo-cross-linked hydrogels. Furthermore, light intensities, wavelengths, and photoinitiator concentrations were tested to achieve tunable photodegradation kinetics. Temporal control of photodegradation was demonstrated, and the hydrogels remained stable postdegradation. Lastly, spatial control of photodegradation was achieved by patterning complex geometries onto 3D-printed PEGaNB_CA hydrogels. Taken together, this work presents a facile synthesis route to prepare PEGaNB_CA, which can be readily photo-cross-linked into modular and photodegradable hydrogels without the need for a special photolabile motif.