Hybrid endometrial-derived hydrogel and human endometrial organoids synergize for uterine regeneration in an immunocompetent murine model

• A hybrid hydrogel combining PuraMatrix® and endometrial extracellular matrix (EndoECM) provides a biocompatible and mechanically stable scaffold for human endometrial organoid delivery in vivo. • Co-injection of human endometrial organoids with the hybrid hydrogel significantly improved endometrial thickness, gland density, and vascularization while reducing fibrosis and ferroptosis in a murine model of uterine damage. • The dual regenerative strategy did not fully restore fertility outcomes, likely due to incomplete resorption of the synthetic hydrogel component, highlighting the need for optimization of hydrogel degradation. • This study provides the first in vivo evidence of the synergistic potential of endometrial organoids and hybrid hydrogels for uterine regeneration, paving the way for future translational research.