A microfluidic-engineered vascularized endometrium micro-organoid platform for functional repair of intrauterine adhesion.

Abstract

Intrauterine adhesion (IUA) is a prevalent gynecological disorder characterized by endometrial fibrosis and compromised regeneration, with a lack of effective clinical treatments. Here, we present a microfluidic biofabrication strategy to engineer vascularized endometrial micro-organoids that recapitulate the cellular complexity and function of native tissue. By co-encapsulating human endometrial stromal cells, epithelial organoids, and endothelial cells (HUVECs) in biocompatible hydrogel microspheres, we created 3D constructs supporting hormone responsiveness, decidualization, and pathological remodeling upon transforming growth factor-<i>β</i>stimulation. Transcriptomic profiling and single-cell sequencing revealed that the presence of endothelial cells alleviated hypoxia-induced inflammation and promoted epithelial homeostasis.<i>In vivo</i>transplantation into a murine IUA model led to improved engraftment, endometrial regeneration, and fertility recovery. This vascularized organoid system offers a scalable and translational platform for endometrial repair and disease modeling, highlighting the promise of biofabrication in reproductive regenerative medicine.