Spatiotemporal piezoelectric microspheres for wireless endometrial repair with improved pregnancy outcomes

Endometrial injury is a pathological damage caused by intrauterine infection, repeated miscarriage, or curettage, which can seriously impair fertility. Effective repair of damaged endometrium is crucial. Traditional interventions often only bring moderate improvements; therefore innovative repair strategies are needed. Herein, we propose a novel spatiotemporally responsive piezoelectric microsphere platform, which could be applied for ultrasound-guided endometrial regeneration and fertility recovery. These microspheres are manufactured by microfluidic technology, producing a core-shell structure: a Chinese herb-laden hydrogel embedded in piezoelectric nanoparticles, and wrapped by a viscous polydopamine (PDA) shell. The herbal hydrogel inhibits the release of inflammatory cytokines, and play the role of phytoestrogen to synergistically enhancing sexual function and tissue repair. The PDA shell scavenges reactive oxygen species (ROS), dampening oxidative stress and chronic inflammation. Meanwhile, the encapsulated gold-decorated tetragonal barium titanates (Au@BTO) nanoparticles generate bactericidal ROS upon ultrasonic activation, ensuring sterile local microenvironments. Vessel-on-a-chip and endometrium-injury rats model confirm the microspheres's outstanding compatibility, and their capacity to stimulate cell proliferation, migration and angiogenesis. Intrauterine delivery of the microspheres accelerates endometrial re-epithelialization, amplifies angiogenesis, restores myometrial integrity, and ultimately preserves fertility. With its precise spatiotemporal control and multimodal therapeutic functions, this microsphere system represents a transformative approach for localized treatment of gynecological diseases.