A recent report from IDTechEx Research states that regenerative medicine will be the biggest growth market for 3D bioprinting. However, while using the technology for the replacement of damaged and failing organs is far more advanced than being purely a fantasy based in the realms of science fiction, the report suggest there are some hurdles to making the technology a significant player in the market, and it may be some years before it can realise its potential.
One of the limits in achieving 3D bioprinted organs for transplant is size. Currently, researchers can create miniaturised tissue resembling natural tissue, but many of these constructs are not capable of achieving therapeutic impact due to their small size. There are several hurdles to creating large 3D bioprinted tissues, as follows:
Though there are a variety of methods to deposit cells in 3D bioprinting, the most popular techniques, and also those available commercially, are still inkjet and extrusion. Both types of printheads feature nozzles, and for that reason, the viscosity of cell-laden bioink must remain low. Cells are sensitive to mechanical stress, which can become significant when cell-laden bioinks are forced through a small orifice such as the printing nozzle. Thus, bioinks are usually shear-thinning, to ensure that cells can be deposited with high viability.
This need for low viscosity during the deposition process is directly in contradiction with the printing of large constructs. To ensure that large structures are appropriately supported, each layer must maintain its shape when printed. However, this is almost impossible with low viscosity bioinks, as they quickly flow and spread after ejection from the nozzle.
Currently, numerous materials and strategies are being explored to cover the conflicting needs of viscosity. A popular strategy is to use biocompatible polymers capable of crosslinking, and research efforts are focused on increasing the speed, reliability and biocompatibility of the crosslinking step. The majority of the research in this area focuses on developing novel functional side groups for existing bioink polymers.
A second hurdle to the fabrication of large 3D bioprinted constructs is the speed at which the tissue can be built. Due to the high resolution of 3D bioprinting, of which droplets can be as small as 20μm in diameter, large constructs may require hours, if not days to complete. The problem here is in maintaining the cells in a physiological environment throughout the long printing process. This involves strict control over the temperature and humidity of the printed construct, as cells are fragile and sensitive to changes in their environment. Therefore, there is a need for both advancements in 3D bioprinters to support the construct, but also in increasing the printing speed.
A third hurdle, and one that is the most often cited, is the need for vasculature in large tissues. Without vasculature to bring nutrients and oxygen to the centre of large tissues, and similarly, to remove the waste, the size of the tissue is limited to the diffusion limit of oxygen, which is approximately 150μm. There are several 3D bioprinting techniques to create artificial vasculature, such as using coaxial nozzles to create tubular structures with sacrificial cores, but it is the complex design of vasculature throughout organs that may prove difficult to replicate through 3D bioprinting.