Modular tissue engineering creates a three-dimensional (3D) macroscale tissue construct from modular microscale units for complex 3D tissue reconstruction. In particular, a hydrogel sheet that is one of the module types allows easy and controllable assembly of 3D microenvironments as compared to other module types such as a microcapsule and a microfiber. However, it is difficult to manipulate a hydrogel sheet made of extracellular matrix (ECM) proteins. Thus, in this study, we propose a fabrication technique for the manipulation of thin collagen sheet containing cells with a paper support. A donut-shaped paper support was combined with the micropatterned collagen sheet by permeation of cell-collagen mixture passing through a micropatterned mold into the paper. We established a sterile method for the paper support to maintain high cell viability and intrinsic cell morphology and demonstrated an endothelial module having 3D tubular networks. The endothelial module also showed that control of the pattern length resulted in a change in the tubular size and network density within a sheet. The geometrically controlled collagen sheet modules are expected to be used for improved implantation and biologically relevant drug testing.
Keywords: 3D tissue; collagen; hydrogel sheet; micropattern; modular tissue engineering.