Enzymatically mediated, physiologically triggered N-palmitoyl chitosan hydrogels with temporally modulated high injectability

Injectable hydrogels ideally are low-viscosity liquids when being pushed through a syringe needle and quickly form gels after injection. Physiologically triggered injectable hydrogels based on stimuli-responsive polymers induce sol to gel transitions via pH or temperature alteration, however, such mild environmental stimuli are often prone to be inefficient for triggering the rapid and drastic transition from low-viscosity liquids to form-stable hydrogels. Here, an enzyme mediation strategy to regulate, transmit, and amplify the environmental stimuli is presented for efficient formation of hydrogels with high injectability and stability. The urease-regulated biocatalytic reaction initially inhibited at slightly acidic pH and room temperature is integrated with a pH-responsive system of aqueous N-palmitoyl chitosan (NPCS), acquiring temporally modulated high injectability. After injection to physiological environments, the enzyme activity is significantly enhanced with the elevated pH and temperature, resulting in fast enzymatic generation of a base, which in turn triggers the efficient hydrogelation of aqueous NPCS.