Densely vascularized thick 3D tissue shows enhanced protein secretion constructed with intermittent positive pressure.

Constructing a dense vascular endothelial network within engineered tissue is crucial for successful engraftment. The present study investigated the effects of air-compressing intermittent positive pressure (IPP) on co-cultured mesenchymal stem cells and vascular endothelial cells and evaluated the potential of IPP-cultured cell sheets for transplantation therapy. The results demonstrated that the IPP (+) group exhibited a denser vascular endothelial network and significantly increased cell sheet thickness compared to the IPP (-) group. Furthermore, in vivo experiments showed that IPP-cultured cell sheets enhanced the secretion of Gaussian luciferase by genetically modified mesenchymal stem cells. These findings highlight the IPP method as a technique that simultaneously enables the thickening of planar tissues and the construction of vascular networks. This approach demonstrates promise for fabricating functional, transplantable, and thick tissues with dense vascularization and a high capacity for protein secretion, paving the way for novel applications in regenerative medicine.