Injectable, Shear-Thinning, Self-Healing, and Self-Cross-Linkable Benzaldehyde-Conjugated Chitosan Hydrogels as a Tissue Adhesive

Benzaldehyde-conjugated chitosan (CH–CBA) was synthesized by a coupling reaction between chitosan (CH) and carboxybenzaldehyde (CBA). The pH-sensitive self-cross-linking can be achieved through the Schiff base reaction. The degree of substitution (DS) of CH–CBA was controlled at 1.4–12.7% by optimizing the pH and reagent stoichiometry. The dynamic Schiff base linkages conferred strong shear-thinning and self-healing properties to the hydrogels. The viscosity of the 2 wt/v % CH–CBA hydrogel decreased from 5.3 × 107 mPa·s at a shear rate of 10–2 s–1 to 2.0 × 103 mPa·s at 102 s–1 at pH 7.4. The CH–CBA hydrogel exhibited excellent biocompatibility in vitro and in vivo. Moreover, the hydrogel adhered strongly to porcine small intestine, colon, and cecum samples, comparable to commercial fibrin glue, and exhibited effective in vivo tissue sealing in a mouse cecal ligation and puncture model, highlighting its potential as a biomaterial for application in tissue adhesives, tissue engineering scaffolds, etc.