The skin, the largest organ of the human body, plays a crucial role in maintaining homeostasis and protecting against external influences. Although it possesses remarkable self-healing capabilities, severe or chronic injuries often necessitate external intervention. In this context, wound management and targeted drug delivery are central areas of biomedical research, where the development of smart biomaterials and the concept of smart wound dressings have revolutionized treatment strategies. Among the various biomaterials, polysaccharide-based wound dressings—particularly dextran-based hydrogels—have gained growing attention due to their excellent biocompatibility, biodegradability, non-toxicity, and clinical safety. Dextran hydrogels exhibit exceptional properties, including high water retention, tunable mechanical strength, and responsiveness to various external stimuli, making them ideally suited for advanced medical applications. This review provides a comprehensive overview of stimuli-responsive polysaccharide hydrogels, with a focus on dextran-based systems. It begins with a discussion of skin structure and function, wound healing mechanisms, and the limitations of chronic and diabetic wounds, highlighting the need for advanced biomaterials. The review then summarizes advances in the design of dextran-based hydrogels, focusing on stimulus responsiveness mechanisms, manufacturing strategies, and crosslinking techniques. Particular attention is paid to their biomedical applications in wound healing and drug delivery, emphasizing mechanisms for controlled release, antimicrobial activity, and tissue regeneration. The review concludes with critical insights into current challenges and future directions for the clinical application of dextran-based hydrogels.
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