Adhesive injectable cellulose-based hydrogels with rapid self-healing and sustained drug release capability for promoting wound healing

Abstract

Injectable biocompatible hydrogels with multiple functions, including self-healing, adhesion, antibacterial activity, and suitable mechanical properties, are highly desirable for enhancing wound healing. In this study, a new class of multi-functional injectable self-healing cellulose-based hydrogels was synthesised using dynamic covalent acylhydrazone linkages for wound dressing. The carboxymethyl cellulose-graft-adipic dihydrazide (CMC-ADH)/4-Formylbenzoic acid-terminated poly(ethylene glycol) (PEG-FBA) (CMC-ADH/PEG-FBA) hydrogels have adjustable gelation time and excellent self-healing ability. In addition, drug release and in vitro antibacterial activities against Gram-positive and Gram-negative bacteria confirmed the sustained drug-release capacity of the hydrogels. Moreover, haemostasis and wound-healing effects were investigated using an in vivo haemorrhaging liver mouse model and a full-thickness skin defect model, and the results indicated that they not only promoted the wound-healing process but also presented excellent haemostatic effects. The CMC-ADH/PEG-FBA gels also exhibited good adhesion to irregular wounds and significantly enhanced angiogenic ability in vivo. This excellent wound-healing performance occurs because hydrogels can quickly stop bleeding, provide a moist and closed environment for the wound to prevent bacterial invasion, release ciprofloxacin (CIP), reduce inflammatory reactions, and promote wound tissue regeneration. In summary, the synthesised multi-functional gels are ideal candidates for treating haemorrhages and irregular wounds.