3D Printing of Stem-Cell Tissue Matrices
Tissue grafts for replacing blood vessels employ several tissue sources. While stem cells (SC) are a highly accessible totipotent/pluripotent stem cell with enormous clinical applications for restituting cardiovascular structures after injury, they are not often used in such grafts. SCs can however differentiate to smooth muscle and endothelial cells, even cardiomyocytes, showing minimal allorecognition and excellent engrafting. Although subcutaneous SC administration restores tissue functions in some models, this approach requires homing and differentiation in host tissues and cannot generate specific complex 3D structures e.g. blood vessels. Blood ‘vessels’ can however be created using collagen matrices, yet scaffold manufacturing integrating SC remains technically challenging and largely untested. Technologies which differentiation SCs in 3D-collagen scaffolds can create individualized ‘on-demand’ tissue grafts based on CT-scans of patient anatomy and MR imaging. This project will incorporate SC into 3D-printed scaffolds and differentiate them to specific lineages to create muscular grafts. This collaboration brings together experts working in smooth muscle/endothelial biology-(Alexander), 3D printing (Mills), stem cell biology (Wang/Dong) and cardiology (Paari) who together will design and fabricate 3D collagen-tissue matrices and analyze properties of these living scaffolds. We will use standard 3D design platforms (CAD/MayaTM) to create scaffolds which will employ differentiated SC to create living vascular grafts containing smooth muscle and endothelial cells. These will be analyzed mechanically (microscopy, strength, burst pressure) and functionally (contractility, blood cell interactions) as a function of time, pharmacological treatment, differentiation and cell type. Once validated, these technologies will provide competitive advantages for national funding and design commercialization.
Principal Investigator: Mills, David -- Biological Sciences
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