Nanohybrid dual-network chitosan-based hydrogels: Synthesis, characterization, quicken infected wound healing by angiogenesis and immune-microenvironment regulation

Infectious wounds are difficult to heal because of vascular damage and immune imbalance. The multi-functional hydrogel dressing can regulate vascular regeneration and immune microenvironment through continuous supply of bioactive ingredients to the wound site, which can effectively accelerate the healing speed of infected wounds. In this work, a multifunctional dual-network hydrogel (QCMOD) with good injectability, stability, self-healing and adhesion was designed by combining methacrylic anhydride-modified quaternized chitosan (QCM) with oxidized dextran (OD) via Schiff base reaction and photo-crosslinked polymerization. Subsequently, MgO/Icariin composite nanoparticles with icariin coating were prepared and loaded in QCMOD hydrogel to establish nanohybrid dual-network chitosan-based hydrogels (QCMOD@MI), which possessed a controlled release of Mg2+ and icariin as well as the ability of guiding physiological behavior in wound healing progress. In vitro results showed the nanohybrid hydrogel reduced bacterial infection and possessed multiple physiological functions including promoting cell migration, angiogenesis and reducing secretion of inflammatory factors. In vivo, the nanohybrid hydrogel showed excellent pro-healing abilities for infected full-thickness wounds by reducing bacterial infections and improving the microenvironment of ischemia and inflammation. This study provides a new paradigm for the design of multifunctional bioactive hydrogels and the obtained hydrogel is expected to become a new type of functional dressing.