Development of cell-laden multimodular Lego-like customizable endometrial tissue assembly for successful tissue regeneration

Abstract

Background: The endometrium, the inner lining of the uterine cavity, plays essential roles in embryo implantation and its subsequent development. Although some positive results were preliminarily archived, the regeneration of damaged endometrial tissues by administrating stem cells only is very challenging due to the lack of specific microenvironments and their low attachment rates at the sites of injury. In this context, various biomaterial-based scaffolds have been used to overcome these limitations by providing simple structural support for cell attachment. However, these scaffold-based strategies also cannot properly reflect patient tissue-specific structural complexity and thus show only limited therapeutic effects. Method: Therefore, in the present study, we developed a customizable Lego-like multimodular endometrial tissue architecture by assembling individually fabricated tissue blocks. Results: Each tissue block was fabricated by incorporating biodegradable biomaterials and certain endometrial constituent cells. Each small tissue block was effectively fabricated by integrating conventional mold casting and 3D printing techniques. The fabricated individual tissue blocks were properly assembled into a larger customized tissue architecture. This structure not only properly mimics the patient-specific multicellular microenvironment of the endometrial tissue but also properly responds to key reproductive hormones in a manner similar to the physiological functions. Conclusion: This customizable modular tissue assembly allows easy and scalable configuration of a complex patient-specific tissue microenvironment, thus accelerating various tissue regeneration procedures.