Extracellular Vesicle-Functionalized DNA Hydrogels as Next-Generation Intelligent Platforms for Wound Healing and...

Extracellular vesicles (EVs) have emerged as promising therapeutic agents for tissue repair due to their intrinsic abilities in intercellular communication, immunomodulation, and regeneration promotion. However, the clinical translation of EV-based therapies for wound healing remains limited by challenges such as rapid clearance, poor retention at the wound site, and uncontrolled bioactivity. Recently, DNA hydrogels have attracted increasing attention as programmable biomaterials with excellent biocompatibility, structural tunability, and stimuli-responsive properties. Integrating EVs with DNA hydrogels offers a novel strategy to construct intelligent therapeutic platforms that enhance EV stability, enable sustained release, and provide spatiotemporal control of therapeutic signaling. In this review, we summarize recent advances in extracellular vesicle-functionalized DNA hydrogels as next-generation platforms for wound healing and management. We discuss the design principles of DNA hydrogels, strategies for EV incorporation and functionalization, and the synergistic mechanisms by which these hybrid systems regulate inflammation, promote angiogenesis, and accelerate tissue regeneration. In addition, emerging intelligent features such as stimuli-responsive release, biosensing capability, and programmable therapeutic delivery are highlighted. Finally, we address current challenges, including large-scale manufacturing, standardization, and translational barriers, and outline future perspectives for the clinical application of EV-functionalized DNA hydrogel systems in regenerative medicine.