Artificial uterus with fluidics-driven system using material-switching digital light processing 3D bioprinting.

Abstract

Despite various attempts to replicate complex organ structures using 3D bioprinting technologies, the fabrication of a tissue-engineered endometrium with integrated vasculature remains a significant challenge in the field. In this study, we developed three bioinks by combining glycidyl methacrylate-modified GelMA (GelMAGMA) hydrogel precursor with endometrial stem cells, stromal cells, and endothelial cells to create a vascularized endometrial construct. Utilizing a one-step material-switching DLP 3D bioprinter capable of multi-material printing, we successfully fabricated an engineered endometrial construct with a vascular channel extending through both the functional and basal layers. The use of a perfusion culture system to circulate medium through the vascular network promoted cell activation, and estrogen treatment further validated the functionality of the construct. Additionally, in vivo subcutaneous implantation demonstrated the biocompatibility of the engineered tissue. This platform offers significant potential for tissue-engineered endometrial implants as well as research into various vascularized implantable tissues. STATEMENT OF SIGNIFICANCE: This study aims to develop a vascularized tissue-engineered endometrium for use in disease research and tissue implantation. Key findings include the development of GelMAGMA-based bioinks, fabrication of a vascularized endometrial construct, validation of its functionality, and proof of biocompatibility. The results advance tissue engineering and personalized medicine, with significant implications for endometrial disease studies and vascularized tissue model development.