Continued Incremental Progress Towards Printed Tissue with Vasculature
Organoid tissues generated by 3D printing are limited in size because it remains challenging to print capillary networks. Without capillaries, nutrients and oxygen can only perfuse a few millimeters into a tissue. Cells will perform some self-assembly, so printed tissue doesn't have to be perfect, but it does need a complex and extensive blood vessel network. This is at present the biggest roadblock on the way to printing entire replacement organs, and has been for more than a decade. It is why considerable effort still goes into the development of alternatives that focus on improving logistics and capabilities for the transplantation industry, such as recellularization of donor organs with patient-matched cells, and xenotransplantation of organs grown in genetically engineered pigs.
"In prior work, we developed a new 3D bioprinting method, known as "sacrificial writing in functional tissue" (SWIFT), for patterning hollow channels within a living cellular matrix. Here, building on this method, we introduce coaxial SWIFT (co-SWIFT) that recapitulates the multilayer architecture found in native blood vessels, making it easier to form an interconnected endothelium and more robust to withstand the internal pressure of blood flow." The key innovation developed by the team was a unique core-shell nozzle with two independently controllable fluid channels for the "inks" that make up the printed vessels: a collagen-based shell ink and a gelatin-based core ink. The interior core chamber of the nozzle extends slightly beyond the shell chamber so that the nozzle can fully puncture a previously printed vessel to create interconnected branching networks for sufficient oxygenation of human tissues and organs via perfusion. The size of the vessels can be varied during printing by changing either the printing speed or the ink flow rates.
The team used a shell ink that was infused with smooth muscle cells (SMCs), which comprise the outer layer of human blood vessels. After melting out the gelatin core ink, they then perfused endothelial cells (ECs), which form the inner layer of human blood vessels, into their vasculature. After seven days of perfusion, both the SMCs and the ECs were alive and functioning as vessel walls - there was a three-fold decrease in the permeability of the vessels compared to those without ECs.
Finally, they were ready to test their method inside living human tissue. They constructed hundreds of thousands of cardiac organ building blocks (OBBs) - tiny spheres of beating human heart cells, which are compressed into a dense cellular matrix. Next, using co-SWIFT, they printed a biomimetic vessel network into the cardiac tissue. Finally, they removed the sacrificial core ink and seeded the inner surface of their SMC-laden vessels with ECs via perfusion and evaluated their performance. Not only did these printed biomimetic vessels display the characteristic double-layer structure of human blood vessels, but after five days of perfusion with a blood-mimicking fluid, the cardiac OBBs started to beat synchronously - indicative of healthy and functional heart tissue.
Link: https://wyss.harvard.edu/news/3d-printed-blood-vessels-bring-artificial-organs-closer-to-reality/