Developing and characterising bovine decellularized extracellular matrix hydrogels to biofabricate female reproductive tissues

Abstract

This study investigated the development and characterization of decellularized extracellular matrix (dECM) hydrogels tailored for the biofabrication of female reproductive tissues, specifically targeting ovarian cortex, endometrium, ovarian medulla, and oviduct tissues. We aimed to evaluate the cytocompatibility, biomechanical properties, and overall efficacy of these dECMs in promoting cell viability, proliferation, and morphology using the bovine model. Bovine species provide a valuable model due to their accessibility from slaughterhouse tissues, offering a practical alternative to human samples, which are often limited in availability. Additionally, bovine tissue closely mirrors certain physiological and biological characteristics of humans, making it a relevant model for translational research. Our findings revealed that these dECMs exhibited high biocompatibility with embryo development and cell viability, supporting micro vascularization and cellular morphology without the need for external growth factors. It is important to note that the addition of alginate was crucial for maintaining the structural integrity of the hydrogel during long-term cultures. These hydrogels displayed biomechanical properties that closely mimicked native tissues, which was vital for maintaining their functional integrity and supporting cellular activities. The printability assessments showed that dECMs, particularly those from cortex tissues, achieved high precision in replicating the intended structures, though challenges such as low porosity remained. The bioprinted constructs demonstrated robust cell growth, with over 97% viability observed by day 7, indicating their suitability for cell culture. This work represented a significant advancement in reproductive tissue biofabrication, demonstrating the potential of dECM-based hydrogels in creating structurally and viable tissue constructs. By tailoring each dECM to match the unique biomechanical properties of different tissues, we paved the way for more effective and reliable applications in reproductive medicine and tissue engineering.

Statement of Significance

This research explores the use of decellularized extracellular matrix (dECM) hydrogels as bio-inks for creating reproductive tissues. Ovarian cortex and medulla, oviduct and endometrium dECMs demonstrated biomechanical properties that mimicked native tissues, which is essential for maintaining functional integrity and supporting cellular processes. Notably, these hydrogels exhibited high biocompatibility with embryo development and cell viability, promoting microvascularization and cell differentiation without the need for supplemental growth factors. The successful bioprinting of these bio-inks underscores their potential for creating more complex models. This work represents a significant advancement in tissue engineering, offering promising new avenues for reproductive medicine.