In this project, we have successfully developed a 3D bioprinting technology to create functional cardiac tissues via encapsulation of cardiomyocytes derived from human embryonic stem cells (hESC). To further improve their viability and cardiac functionality, we have developed a new vascularization strategy to enhance the cardiac tissue model through the incorporation of functional vasculature using 3D bioprinting. We have tested these 3D-printed cardiac patch and scaffolds in mice. Results have shown that these biomaterials are compatible with in vivo applications. Such advanced 3D bioprinting tool and techniques could be translatable for future clinical applications.
In Specific Aim 1, we have successfully developed and optimized the rapid 3D bioprinting technique to create biomimetic 3D micro-architectures using hyaluronic acid (HA)-based biomaterials and hESC-derived cardiomyocytes. We have successfully measured the physiological function of cells embedded within the hydrogel constructs. We further investigated the mechanical forces of the beating heart tissues by cantilever displacement. Additionally, we have measured calcium transients in our 3D printed tissue constructs by live confocal imaging at varying frequencies. In Specific Aim 2, we have created an advanced vascularization techniquefor 3D pre-vascularized cardiac tissues with precise control of spatial organization. Cells in this bioprinted configuration showed proliferation and viability. In Specific Aim 3, we implanted the 3D bioprinted pre-vascularized cardiac tissue in mouse models. Results shows that these cardiac tissues can integrate well with the host tissue.