Chitosan–Lysozyme Conjugates for Enzyme-Triggered Hydrogel Degradation in Tissue Engineering Applications

Tuning hydrogel degradation enables effective and successful tissue regeneration by modulating cellular behaviors and matrix formation. In this work, we develop a novel degradable hydrogel scaffold on the basis of a unique enzyme-substrate complex by photocrosslinking. Chitosan and lysozyme are chemically modified with methacrylate moieties to be tethered in hydrogels, and in the presence of riboflavin initiator, these hydrogels are cured by blue light irradiation. The incorporation of lysozyme to chitosan hydrogels accelerates the degradation rate of the crosslinked hydrogels in a dose-dependent manner, as evidenced by an increase in pore size and interconnectivity through cryogenic scanning electron microscopy over time. Those noncytotoxic materials significantly enhance cellular proliferation and migration, which contribute to osteogenic differentiation of encapsulated mesenchymal stem cells in vitro and bone formation in mouse calvarial defects. These findings suggest a promising strategy to modulate the degradation behavior of hydrogels for use in tissue engineering.