Piezo-herbal microneedle patches enable wireless endometrial regeneration and fertility recovery
摘要
Endometrial injury is a major cause of female infertility and recurrent miscarriage. Conventional treatments often fail to dynamically regulate the local immune microenvironment or effectively promote angiogenesis and functional regeneration. Here, we developed an ultrasound-responsive microneedle (MN) patch for wireless endometrial repair, integrating the natural compound curcumin and piezoelectric potassium sodium niobate (KNN) nanoparticles into a photopolymerized hydrogel. This design enables spatiotemporally controlled drug release, antioxidant activity, and piezoelectric stimulation under ultrasound activation. In vitro, the Cur@KNN MN exhibited excellent biocompatibility, potent reactive oxygen species scavenging, anti-inflammatory effects, and pro-angiogenic capacity, as validated in macrophage and vascular-on-a-chip models. In a rat endometrial injury model, implantation of the patch combined with ultrasound exposure promoted KNN-mediated microcurrent generation, which synergistically enhanced curcumin release and significantly improved regeneration of smooth muscle and microvessels. Notably, the treated endometrium showed increased thickness, reduced fibrosis, and restored fertility, with a marked increase in embryo implantation rates. These results demonstrate that the traditional Chinese medicine-based piezoelectric MN system not only supports structural reconstruction of the injured uterus but also effectively restores reproductive function, offering an innovative and minimally invasive strategy for in situ tissue regeneration.
Graphical Abstract