Ling Jiang, Xuemei Wang, Hui Jiang
Despite the great self-regeneration ability of skin, severe defects require the intervention of functional dressings for effective healing. Hydrogels are ideal candidates for wound administration because of their high hydration, structural porosity, and extracellular matrix mimicking properties. Chitosan (CS) is the core matrix for building hydrogels because of its inherent biocompatibility, oxygen permeability, hemostatic, and antimicrobial activities. Through reversible cross-linking strategies with dynamic covalent bonds (e.g., Schiff base and borate-diol) and physical interactions (hydrogen bonding, electrostatic interactions, and host-guest interactions, etc.), CS-based hydrogels can dynamically adapt to the complex microenvironment of wounds. In recent years, researchers have developed smart CS hydrogel dressings with biocompatible and biodegradable, hemostatic/adhesive, antimicrobial, antioxidant, anti-inflammatory, stimulus-responsive (pH/temperature/glucose), controlled-release, and self-healing functionalities in response to diverse needs during wound healing. In acute wounds, its rapid hemostatic and infection control properties significantly accelerate healing, while for chronic wounds (e.g., drug-resistant bacteria-infected wounds, deep burns, and diabetic ulcers), it breaks down healing barriers through synergistic mechanisms including photothermal, antimicrobial, macrophage polarization modulation, reactive oxygen species scavenging, and vascular regeneration promotion. This article contains a comprehensive review of the design principles, functional optimization, and the recent progress of CS-based hydrogels for wound healing, as well as a further outlook on the future direction of hydrogel dressings in wound treatment.