Imagine having the power to communicate directly with cells, commanding a vat of cellular liquid to form an intricate biological construct. While this seems like an ideal mechanism for ordering a hot meal à la Star Trek replicator, it turns out this is being done today by a number of research labs around the world, thanks to a bioprinting technique that relies on light to control the formation of biomaterial structures.
2016 was named the year for additive manufacturing in the medical sector, and 3D printing in the medical industry has already seen great advances in the production of orthopedic devices, prosthetics, dental implants, and 3D models for surgical assistance and preparation. Simultaneously, bioprinting is advancing rapidly, having achieved recent breakthroughs such as the ability to 3D print blood vessels, placental tissue, and stem cells, as I’ve previously written about.
Today I want to focus on a new and evolving technique: light-assisted bioprinting. Though it has some limitations to overcome – it’s still in its early days – it has already demonstrated that it is a serious contender for future bioprinting development due to its unique ability to produce biological structures with micro- and nano-scale precision. This fascinating innovation has great potential to support medical, bioengineering, and biochemistry research as it is the only bioprinting method capable of producing structures at single-cell resolution. Let’s take a look at how it works, and its applications.
How Light-Assisted Bioprinting Works
Light-assisted bioprinters fuse biomaterials into functional 3D scaffolds, similar to the way industrial 3D printers leverage light to fuse plastic filament in stereolithography and metal powders in selective laser sintering. Until recently, bioprinting has relied mainly on inkjetting and extrusion-based methods. The vast majority of commercially available bioprinters utilize one or both of these methods to deposit biomaterial onto a build plate or into a micro-well.
In contrast, light-assisted bioprinting relies on laser energy to trigger polymerization of photosensitive biomaterials contained in a vat or tank. These materials are hydrogels laden with cells that form crosslinked chemical bonds when stimulated with light. Software is used to deconstruct a 3D model into 2D slices, which are then either imaged by a UV laser and a DMD projector in sequence onto the surface of the hydrogel, or else traced one voxel at a time by an infrared femtosecond laser. A motorized stage manipulates the sample in stages until the fabrication is complete, and the model builds progressively layer-by-layer. UV and infrared light are utilized most often as these provide the best rates of cell viability during and after light exposure.
How Are Light-Assisted Bioprinters Unique?
- Scale: Through light-assisted bioprinting, it is possible to generate biological structures, such branching blood vessels, just 1 micron thick. This is a monumental feat, and enables the generation of biomaterial scaffolds with precise micro- and nano-architectures controllable at the voxel level. Such precision can much more accurately imitate native tissues, enabling greater degrees of biomimicry. This is useful in single-cell studies, such as examining cell division rates in cancer cells.
- Mechanical and Chemical Tuning: The scaffolds light-assisted bioprinting produces are tunable across a variety of mechanical and chemical factors including stiffness, elasticity, porosity, swelling, and topography. Researchers can thus control a range of physical attributes, including a scaffold’s response to tensile pressure such that it expands under stress, as native blood vessels do. It is crucial for bioprinted tissues to behave as native tissues do in order to ensure accuracy in drug testing and the study of disease models.
- Speed: Projection-based light-assisted bioprinters (those that project 2D slices onto biomaterial through a DMD projector) are capable of printing entire scaffolds in seconds. This is a truly amazing ability that can be utilized in many current applications of bioprinting. Unfortunately the same is not true of the more precise, femtosecond laser-based light-assisted bioprinters, whose greatness weakness is speed – they can take several hours to print a part. Further development in optics and biomaterials may help address this limitation.
Organs-on-Chips are small devices that emulate entire organ function and are made of polymer chips engraved with microfluidic channels, lined with living cells in specific configurations. A lung, heart, kidney, and most recently cancer metastasis have been modeled on chips, and the list continues to grow.
Organs-on-Chips provide a highly useful tool for studying the effects of drugs and toxins as well as the development of pathophysiology. The degree of control researchers have over the experimental environment is greatly enhanced in comparison with native organs, and studies can be undertaken that would not be ethical in other contexts, such as purposefully infecting live lung tissue with cancer cells so as to study its evolution, and gain insights for future treatments. Organs-on-chips are currently being used to help researchers find a cure for several diseases, including Hepatitis B.
Though they have many advantages, organs-on-chips currently lack biological similitude to their native organ counterparts. Thanks to its unique precision and ability to produce tissues with tunable chemical and mechanical properties, light-assisted bioprinting could be utilized for the fabrication of biologically accurate organs-on-chip systems, thus improving their predictive value to drug developers and biomedical researchers. Researchers at Wake Forest Institute of Regenerative Medicine already plan to improve the bio-similitude of their organs-on-chips using 3D printing. The Institute said in a statement, “When cancer spreads in the human body, the tumor cells must break through blood vessels to enter the blood steam and reach other organs… [We] plan to add a barrier of endothelial cells, the cells that line blood vessels, to the model. We are trying to make it as realistic as we can.”
The potential for bioprinting to improve medical outcomes is truly awe-inspiring. As the field develops, I’m sure there will be many more applications that we can only imagine today. What do you think bioprinting could be used for in the future? I’d love to hear your thoughts in the comments.