Light-responsive liposomes for on-demand degradation of cellulose-based hydrogels

Nanocellulose hydrogels have limited biodegradability under physiological conditions, restricting applications that require controlled scaffold degradation or removal. Here, we present a light-triggered liposomal hydrogel platform that enables localized, on-demand release of cellulase enzyme to induce controlled degradation of anionic cellulose nanofiber (aCNF) hydrogels and cellulose-polysaccharide interpenetrating polymer network (IPN) hydrogels. Cellulase was encapsulated in reactive oxygen species (ROS)-sensitive stimuli-responsive liposomes containing a photosensitizer and incorporated into a hydrogel matrix, allowing external light illumination to trigger enzyme release. To preserve cellulase activity, we established a liposome preparation workflow by systematically assessing formulation and processing parameters that influence enzyme stability. Following light activation and 24 h of incubation under physiological conditions, reducing-sugar levels reached approximately 34% and 40% of the corresponding positive-control levels for the aCNF and IPN liposomal hydrogel systems, respectively. To understand ROS-induced liposome membrane destabilization, a lipid bilayer exposed to hydrogen peroxide was analyzed using high-speed atomic force microscopy (HS-AFM), revealing time- and concentration-dependent degradation. Overall, the developed platform enables externally triggered cellulase-mediated degradation of hydrogels while protecting the enzyme prior to activation, providing a strategy to overcome the limited physiological degradability of cellulose-based scaffolds.