Fig. 1

The basic concept of a Lego-like multimodular tissue assembly recapitulates the multicellular structural complexity of human endometrial tissue. The basic concept of this study is to develop customized multimodular endometrial tissue architectures by assembling individual tissue blocks that encapsulate certain endometrial cell types according to patient-specific tissue microenvironments or injured tissue requirements. As a first step for this object, various cell types constituting the human endometrial tissue were isolated or established (A). Each tissue block (module) encapsulating individual endometrial cells was synthesized by casting using a 3D printed PLA mold to effectively and stably produce a large amount of tissue blocks. Briefly, the biomaterial mixture (collagen and hyaluronic acid) with coagulation factors (fibrinogen and thrombin) and approximately 1 × 10⁶ endometrial cells were mixed and injected into a 3D printed PLA mold and then polymerized and cooled to room temperature for 1 h. The polymerized individual tissue blocks were effectively released from the PLA mold by slowly pushing them with a separator (B). Next, individually synthesized tissue blocks were assembled into the multimodular endometrium architecture by inserting them into multiple empty slots on the assembly sheet based on patient-specific tissue microenvironments or injured tissue requirements (C). Finally, the multimodular endometrial tissue assembly encapsulating various endometrial cells was directly transplanted into the tissue injury mouse model, and its therapeutic effects were analyzed in vivo(D)