Hydrogel-based regulation of neutrophil extracellular traps: from wound healing to multi-system disease management

Inflammatory and immune-mediated diseases represent a major global health challenge, urgently demanding novel therapeutic targets. Neutrophil extracellular traps (NETs) are reticular structures released by neutrophils. As a vital component of innate immunity, NETs physically trap and eliminate invading pathogens. However, excessive NETs activation or impaired clearance drives the pathogenesis of various diseases. These aberrant processes exacerbate inflammation, trigger autoimmune disorders, impair wound healing, and promote thrombosis. Furthermore, they create a microenvironment that facilitates cancer metastasis and immune evasion. Consequently, targeted interventions against NETs have emerged as promising therapeutic strategies for these conditions. In this context, hydrogels exhibit enormous application potential due to their excellent biocompatibility and superior drug controlled-release capabilities. This review introduces NETs formation pathways, comprehensively summarizes cutting-edge hydrogel-based NETs-targeting therapies across various diseases, and discusses integrated hydrogel design strategies, aiming to provide new insights for the development of more efficient and intelligent targeted NETs therapy.