Hybrid Endometrial-Derived Hydrogels: Human Organoid Culture Models and In Vivo Perspectives.

The endometrium plays a vital role in fertility, providing a receptive environment for embryo implantation and development. Understanding the endometrial physiology is essential for developing new strategies to improve reproductive healthcare. Human endometrial organoids (hEOs) are emerging as powerful models for translational research and personalized medicine. However, most hEOs are cultured in a three-dimensional microenvironment that significantly differs from the human endometrium, limiting their applicability in bioengineering. In this study, we present a hybrid endometrial-derived hydrogel that combines the rigidity of PuraMatrix with the natural scaffold components and interactions of a decellularized porcine endometrial extracellular matrix hydrogel. This hydrogel provides outstanding support for hEO culture, enhances hEO differentiation efficiency due to its biochemical similarity with the native tissue, exhibites superior in vivo stability, and demonstrates xenogeneic biocompatibility in mice over a two-week period. Taken together, these attributes position this hybrid endometrial-derived hydrogel as a promising biomaterial for regenerative treatments in reproductive medicine. This article is protected by copyright. All rights reserved.