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 3D microenvironment that significantly differs from the human endometrium, limiting their applicability in bioengineering. This study presents a hybrid endometrial-derived hydrogel that combines the rigidity of PuraMatrix (PM) with the natural scaffold components and interactions of a porcine decellularized endometrial extracellular matrix (EndoECM) hydrogel. This hydrogel provides outstanding support for hEO culture, enhances hEO differentiation efficiency due to its biochemical similarity with the native tissue, exhibits superior in vivo stability, and demonstrates xenogeneic biocompatibility in mice over a 2-week period. Taken together, these attributes position this hybrid endometrial-derived hydrogel as a promising biomaterial for regenerative treatments in reproductive medicine. This work presents a novel hybrid endometrial-derived hydrogel that combines the rheological properties of PM with the biochemical cues of porcine EndoECM hydrogel. This hydrogel not only provides a suitable support for hEO culture and differentiation, but also exhibits in vivo compatibility and stability, presenting it as a promising biomaterial for regenerative treatments in reproductive medicine.image