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

Abstract

ABSTRACT 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.