Intrauterine adhesion (IUA) is a prevalent gynecological disorder characterized by endometrial fibrosis and compromised regeneration, lacking 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 TGF-β stimulation. Transcriptomic profiling revealed that the presence of endothelial cells alleviated hypoxia-induced inflammation and promoted epithelial homeostasis. In vivo 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.
GU et al. (Mon,) studied this question.