Smart hydrogel dressings for advanced wound healing: from biomaterial design to microenvironment modulation

Complex wounds, such as severe burns and chronic diabetic ulcers, pose substantial clinical challenges due to dysregulated healing processes involving persistent inflammation, oxidative stress, and bacterial infection. Conventional dressings offer limited therapeutic efficacy, creating an urgent demand for advanced materials capable of actively participating in the healing cascade. Hydrogels have emerged as leading candidates, attributed to their structural similarity to the native extracellular matrix high water content, and tunable physicochemical properties. This review provides a comprehensive overview of recent innovations in “smart” hydrogel dressings designed to modulate the wound microenvironment and promote regenerative healing. We discuss the evolutionary trajectory of hydrogel materials, ranging from natural and synthetic polymers to novel bio-inspired systems such as DNA-based and peptide hydrogels. A central focus is placed on engineering multifunctionality, including stimulus-responsive drug delivery, inherent antimicrobial and antioxidant activities, immunomodulatory capabilities, and enhanced mechanical properties (e.g., self-healing and tissue adhesion). Furthermore, we explore how these advanced hydrogels target specific pathological hallmarks of complex wounds, including macrophage polarization, angiogenesis, cellular senescence, and fibrosis, to facilitate not only wound closure but also complete tissue regeneration (including appendages). Finally, we highlight the current challenges in clinical translation (including manufacturing scalability, terminal sterilization, regulatory approval, batch-to-batch reproducibility, and cost) and discuss future perspectives, including the development of theranostic platforms (integrated diagnostic and therapeutic systems) and personalized wound care solutions based on patient-specific ROS, immune, and pH profiles.