Towards Faster Bioprinting of Replacement Tissue
3-D tissue printing has been a work in progress for going on twenty years at this point. The biggest challenges are (a) that it remains slow and expensive, and (b) producing sufficient microvasculature to support the printed tissue. Inroads are being made on both of these issues, such as the work noted here, but progress is incremental. It remains to be seen as to when the much anticipated 3-D printed organs made from a patient's own cells and ready for transplantation will emerge - at this point, the creation of functional tissues much larger than a few millimeters is not a practical proposition for most use cases.
Bioprinting allows researchers to build 3D structures from living cells and other biomaterials. Living cells are encapsulated in a substrate like a hydrogel to make a bioink, which is then printed in layers using a specialized printer. These cells grow and proliferate, eventually maturing into 3D tissue over the course of several weeks. However, it's difficult to achieve the same cell density as what's found in the human body with this standard approach. That cell density is essential for developing tissue that's both functional and can be used in a clinical setting. Spheroids, on the other hand, offer a promising alternative for tissue bioprinting because they have a cell density similar to human tissue.
While 3D printing spheroids offers a viable solution to producing the necessary density, researchers have been limited by the lack of scalable techniques. Existing bioprinting methods often damage the delicate cellular structures during the printing process, killing some of the cells. Other technologies are cumbersome and don't offer precise control of the movement and placement of the spheroids needed to create replicas of human tissue. Or the processes are slow.
To address these issues, researchers developed a new technique called High-throughput Integrated Tissue Fabrication System for Bioprinting (HITS-Bio). HITS-Bio uses a digitally controlled nozzle array, an arrangement of multiple nozzles that moves in three dimensions and allows researchers to manipulate several spheroids at the same time. The team organized the nozzles in a four-by-four array, which can pick up 16 spheroids simultaneously and place them on a bioink substrate quickly and precisely. The nozzle array can also pick up spheroids in customized patterns, which can then be repeated to create the architecture found in complex tissue. To test the platform, the team set out to fabricate cartilage tissue. They created a one-cubic centimeter structure, containing approximately 600 spheroids made of cells capable of forming cartilage. The process took less than 40 minutes, a highly efficient rate that surpasses the capacity of existing bioprinting technologies.