NIR-II-Responsive Hydrogel with Integrated All-in-One Nanotherapeutics for Immunomodulation and Regeneration of Infected Tissues or Bone

Abstract

Bacterial infection is now a significant obstacle to the effective repair and regeneration of both soft tissues and bone in clinical settings. Managing infected sites is challenging due to multiple antimicrobial resistance, abnormal inflammatory responses, and an excessive inflammatory microenvironment. To meet the complex healing needs following soft tissue or bone, an immunomodulatory thermosensitive hydrogel was designed and synthesized. The composite hydrogel (CQDs@UPDA@gel) combines carbon quantum dots (CQDs) as the second near-infrared window (NIR-II) photothermal agents (PTAs) and ultrasmall polydopamine nanoparticles (UPDA NPs) as reactive oxygen species (ROS) scavengers and immunomodulators, embedded within a chitosan matrix coordinated with Cu²⁺ that enhances the good swelling performance and stable rheological properties of the hydrogel. This synergistic approach simultaneously inhibits bacterial infection and alters the immunosuppressive microenvironment, thereby promoting coordinated soft tissue or bone regeneration. In vivo studies have shown that the hydrogel can encourage the regeneration of soft tissue or bone under NIR-II laser irradiation for the treatment of infectious wounds, subcutaneous abscesses, and infectious bone defects in the maxillofacial region. Overall, this project offers a general strategy for creating multifunctional hydrogels that both eradicate pathogens and modulate the immune microenvironment to support the repair of complex soft tissue or bone infections.