Microenvironment-Responsive Hydrogels for Burn Wound Healing: From Molecular Design to Therapeutic Applications

This is the authors' abstract. We don't add key points for this paper.

Burn wounds exhibit a dynamic and heterogeneous microenvironment characterized by altered pH, excessive reactive oxygen species (ROS), dysregulated protease activity, and infection-associated signals, providing potential triggers for stimuli-responsive hydrogels. However, in vitro responsiveness does not necessarily indicate effective activation under actual burn conditions, and therapeutic efficacy in burn models alone cannot confirm in situ triggering. This review therefore examines burn-responsive hydrogels through the framework of microenvironmental signal–material response–network transformation–therapeutic output. We discuss endogenous signals, including pH, ROS, and matrix metalloproteinases, together with externally controllable stimuli such as temperature, near-infrared light, and ultrasound. Molecular functionalization, dynamic crosslinking, and multi-network architectures are analyzed in relation to wound adaptability and therapeutic outputs, including antibacterial activity, oxidative-stress regulation, and tissue regeneration. Particular emphasis is placed on distinguishing material-level responsiveness, therapeutic efficacy in burn models, and in situ activation within the burn microenvironment. Future studies should quantitatively match pathological signal ranges with material activation thresholds while balancing response fidelity, wound adaptability, biosafety, manufacturability, and long-term therapeutic efficacy to facilitate clinical translation.