Dynamically Crosslinked Carbon Dot/Alginate Hydrogels for On-Demand Osteomyelitis Therapy.

Osteomyelitis remains a refractory orthopedic disease; it is urgent to develop osteomyelitis-microenvironment-responsive, dynamic-crosslinked hydrogels that could fight infection, regulate inflammation, and accelerate bone repair simultaneously for on-demand osteomyelitis therapy. Herein, we report an all-in-one hydrogel design based on a highly biocompatible, covalently interlinked, and multifunctional carbon dot (CD) platform for simultaneous regulation of antibacterial, anti-inflammatory, and osteogenic activities while enabling bacteria-specific and controllable release of CDs. To achieve this aim, CDs was significantly modified with two structural factors, i.e., catechol grafted at the edge and Se─Se bonds doped in the core, which play crucial roles in the precise regulation of their multiple functions for on-demand osteomyelitis therapy. Dynamically crosslinked composite hydrogels with dissociable borate ester bonds were constructed by utilizing catechol-functionalized Se-doped CDs as a triple bioactive ingredient. The CD-based composite hydrogels were demonstrated to enable near-complete healing of bone defects in a MRSA-induced osteomyelitis model. This work provides a paradigm for fabrication of dynamic-crosslinked hydrogels from multifunctional CDs for on-demand osteomyelitis therapy.