Zinc oxide nanoparticles (ZnO) have attracted much attention as promising antibacterial agents due to their ability to generate reactive oxygen species (ROS) that effectively eliminate bacteria. However, when they are delivered inside the body, this distinct characteristic of ROS is restricted due to the limited penetration depth of external light, which is required for the photocatalysis of particles. To produce ROS without any light source when the particles are implanted, we introduced catechol-ZnO complexes to a hyaluronic acid (HA) hydrogel platform, which can self-generate sufficient ROS in the bacteria-infected tissue. Catechol-ZnO complexes enhanced ROS generation via electron transfer from the formation of complexes and o-semiquinone, and a hydrogel structure was created by coordinate bonds between functionalized catechol groups in HA and ZnO simultaneously. This hydrogel demonstrated different behaviors in terms of physical properties compared to chemically cross-linked HA hydrogels containing ZnO. This hydrogel showed a higher swelling ratio, enzymatic degradation resistance, and tissue adhesive strength. Enhanced ROS generation was confirmed using electron paramagnetic resonance (EPR), H2O2 concentration, glutathione depletion, and intracellular ROS detection. The improved antibacterial performance of hydrogels from ROS production was also confirmed through in vitro bacterial testing against two bacterial strains, E. coli and S. aureus. Furthermore, an in vivo experiment using an infected mouse model to analyze colony formation, histologic analysis, and hematological inflammatory markers revealed the effective antibacterial effects of catechol-ZnO complexes. Overall, the potential of the hydrogel created via catechol-ZnO complexes for antibacterial therapy was demonstrated through the capability to enhance ROS generation and eradicate bacteria.

Currently, dermal fillers are largely based on commercialized cross-linked hyaluronic acid (HA) injections, which require a large injection force. Additionally, HA can be easily decomposed by enzymes, and HA-treated tissues present a risk of developing granuloma. In this study, a chitosan-based dermal filler is presented that operates on a liquid-to-gel transition and allows the injection force to be kept ≈4.7 times lower than that required for HA injections. Evaluation of the physical properties of the chitosan filler indicates high viscoelasticity and recovery rate after gelation at 37 °C. Furthermore, in an in vivo evaluation, the liquid injection-type chitosan filler transitions to a gel state within 5 min after injection into the body, and exhibits a compressive strength that is ≈2.4 times higher than that of cross-linked HA. The filler also exhibits higher moldability and maintains a constant volume in the skin for a longer time than the commercial HA filler. Therefore, it is expected that the chitosan filler will be clinically applicable as a novel material for dermal tissue restoration and supplementation.

Two-dimensional (2D) histopathology based on the observation of thin tissue slides is the current paradigm in diagnosis and prognosis. However, labeling strategies in conventional histopathology are limited in compatibility with 3D imaging combined with tissue clearing techniques. Here, we present a rapid and efficient volumetric imaging technique of pathological tissues called 3D tissue imaging through de novo formation of fluorophores, or 3DNFC, which is the integration of citrate-based fluorogenic reaction DNFC and tissue clearing techniques. 3DNFC markedly increases the fluorescence intensity of tissues by generating fluorophores on nonfluorescent amino-terminal cysteine and visualizes the 3D structure of the tissues to provide their anatomical morphology and volumetric information. Furthermore, the application of 3DNFC to pathological tissue achieves the 3D reconstruction for the unbiased analysis of diverse features of the disorders in their natural context. We suggest that 3DNFC is a promising volumetric imaging method for the prognosis and diagnosis of pathological tissues.