Microfluidic‐Based Catalytic Nanosponge as an Anti‐NETs Therapeutic to Restore Ovarian Function

Abstract Premature ovarian insufficiency (POI) is a causeof infertility and endocrine dysfunction in women, defined by loss of ovarianfunction before the age of 40 years. Neutrophil extracellular traps (NETs) havebeen implicated in the pathogenesis of POI, as they can promote the release ofcytokines that contribute to oxidative stress, inflammation, and fibrosis, leading to ovary dysfunction. Therefore, NETs represent a promising therapeutictarget for POI. However, research focused specifically on NETs degradationremains limited. In this study, a novel bioinspired catalytic nanosponge basedon microfluidics (DENase@Ce) is proposed as a potential anti‐NETs therapeuticfor POI treatment. Nanosponge coated with cationic polymer enables the captureof NETs via charge‐trapping effects, which can be degraded by outer conjugatedDNase I. To fundamentally alleviate inflammatory microenvironment that recruitsand activates neutrophils, the nanosponge exhibiting intrinsic multienzyme activitiescan effectively reduce the overproduced reactive oxygen species, therebysuppressing NETs further formation. In vivo studies demonstrate that injectionof catalytic nanosponge can rescue ovarian function in mice withcyclophosphamide‐induced ovarian insufficiency, as evidenced by increasedovarian weight, improved follicle counts, and restored fertility. Our workestablishes a novel synergistic anti‐NETs paradigm and presents a promisingtherapeutic platform for addressing chemotherapy‐induced fertility impairment.