Enzymatically Triggered Deprotection and Cross-Linking of Thiolated Alginate-Based Bioinks

Thiolated polymers are widely used in hydrogels for drug delivery, tissue engineering, and biofabrication. The oxidation of thiols is spontaneous, resulting the formation disulfide bridges cross-linking polymers. process is, however, difficult to control initiated directly when thiolated components exposed ambient conditions, which significantly complicates handling materials. Here, we show a fully bioorthogonal enzyme-mediated thiol-based chemistry dynamic covalent carbohydrate-based that circumvents problems with uncontrolled thiol oxidation. Alginate was modified cysteine residues, protected by an enzyme-labile thiol-protecting group (Phacm). Releasing Phacm penicillin G acylase generates free oxidize under physiological reversible tunable stiffness. Prior deprotection, can be conditions. enzyme-triggered deprotection subsequent gelation allows encapsulation cells 3D bioprinting cell-laden hydrogel structures. Remaining deprotected enabled postprinting modifications self-healing. proposed synthesis strategy increases versatility chemistries provides new possibilities generate broad range biomedical applications.