Simultaneous Cross-Linking and Nanoparticle Anchoring by Dialdehyde Cellulose in Injectable Composite Chitosan/Polypyrrole Hydrogels

Abstract

The injectable composite hydrogel with covalently bound polypyrrole (PPy) has been prepared using dialdehyde cellulose (DAC) as a bifunctional cross-linker, forming dynamic imine bonds with water-soluble half acetylated chitosan (SCN) and simultaneously tethering the PPy nanoparticles by aldol condensation. The novelty lies in translating this dual chemistry into an injectable, self-healing hydrogel system, for the first time fully utilizing dynamic Schiff base cross-linking in combination with covalent PPy anchoring. PPy is also involved both in hydrogel cross-linking, altering its rheological behavior, but also providing antioxidative and anti-inflammatory effects. The resulting hydrogels exhibited shear-thinning behavior, rapid self-healing, and storage moduli ranging from 25 to 47 Pa, allowing for injection through 21 G needles. All formulations were noncytotoxic toward NIH/3T3 fibroblasts and RAW 264.7 macrophages. In scratch assays, SCN_DAC_20_PPy significantly accelerated wound closure, with the residual wound area to 39 +/- 2% after 10 h versus 83 +/- 7% for controls and 65 +/- 3% for the corresponding PPy-free hydrogel. In LPS-stimulated macrophages, all hydrogels decreased nitric oxide production, and PPy-containing hydrogels additionally reduced IL-6 secretion. The SCN/DAC/PPy injectable hydrogels thus exhibit cytocompatibility, self-healing properties, and anti-inflammatory activity, representing a promising platform for the future development of advanced wound dressings.