ROS-responsive adaptive injectable hydrogel promoting inflammatory mastoid bone repair through efficient sterilization and regulating oxidative stress and macrophage phenotype

Chronic suppurative otitis media (CSOM) and middle ear cholesteatoma (MEC) are prevalent disorders in the otology specialty. A major challenge is efficiently eliminating dormant opportunistic infections, controlling inflammation, and repairing defected mastoid portion in the middle ear simultaneously to enhance surgical recovery. Herein, a functional injectable polysaccharide-based hydrogel targeting low-cost and easy clinical translation was developed to address bone abnormalities caused by inflammation in the middle ear through introducing a reactive oxygen species (ROS)-sensitive dynamic cross-linked network and catechol groups, which granted it with superb tissue adaptability. The hydrogel could occupy and stick to erratic tissue defects after injection, withstand external forces without damage, and be compliant with tissue movement. In addition, TA@Ag NPs with efficient antibacterial activity were achieved and added to the hydrogel. Moreover, the exceptional biocompatibility and antioxidant features of hydrogel were achieved through reducing catechol groups, and ROS-sensitive dynamic phenylborate link. And the hydrogel reduced fibrosis in faulty area by promptly drawing and aligning macrophages to enhance the immune response for bone regeneration. Thus, the hydrogels facilitate bone structure repair by reducing inflammation, promoting macrophage polarization, eliminating harmful microorganisms, and modulating the immunological and microbial milieu in injured tissues. The hydrogels might be a versatile material for healing defects of mastoid portion bone structure in the middle ear. This novel hydrogel shows great potential for treating chronic otitis media, a condition characterized by structural damage that is difficult to cure.