Exploring the World of 3D Bioprinters

In the realms of science fiction, we've witnessed awe-inspiring technologies that defy the boundaries of imagination. From the mesmerizing replicators aboard the Starship Enterprise to the birth of a cloned dinosaur in Jurassic Park, these cinematic wonders have tantalized our sense of possibility. Yet, what if I told you that one of these remarkable concepts has taken a quantum leap into reality? Welcome to the world of 3D bioprinting, where science fiction meets groundbreaking science facts, and the boundaries of possibility are redrawn with every layer.

3D bioprinting, a revolutionary technique, combines the engineering genius of 3D printing and the potential of biological sciences, to print complex, functional tissue and organ systems using building blocks like cells. No, you did not read that wrong. Yes, you can print entire fully functional organs using a 3D bioprinter. It can do wonders for those unfortunate folks stuck on the long, nightmarish waiting lists for organ transplants. It’s definitely no wonder that 3D bioprinting finds applications in healthcare, regenerative medicine as well as in research. We have previously published an article on the basics of 3D bioprinting. You can read it here.

In this article, we shall explore the wonderful world of 3D bioprinting by looking at the different types of 3D bioprinting along with their merits and limitations. Hold on to your hats!

Before we dig deeper into bioprinters and their types, let's learn a little bit about bioinks. Bioink is essentially a combination of cells and a polymer, natural or synthetic, along with biocompatible constituents facilitating good rheology to enable the adhesion, proliferation, and differentiation of the cells. Multiple formulations of bioinks exist varying in their cell types, polymer types, and the associated growth factors [8]. It is crucial that bioink formulations are optimized to ensure cell viability and growth while not compromising printability and mechanical strength [7].

The following characteristics are vital for a functional bioink formulation: [9]

1. It should be able to create strong and robust tissue structures.
2. It should be adjustable in terms of its gelation while maintaining stability to be able to construct structures with high shape fidelity.
3. It should be biocompatible and in some cases, biodegradable.
4. Furthermore, it should be amenable to chemical modifications based on the requirements of the tissue
5. The bioink should pass the test of scalability to generate a large number of products with minimal variations.

Types of 3D Bioprinters

Inkjet Bioprinters

Inkjet bioprinters operate on a similar principle to traditional inkjet printers but use bioinks containing cells and biomaterials. This is a non-contact jetting-based printing technique wherein printers deposit tiny droplets of bioink layer by layer to build 3D structures [1]. There are two types of inkjet bioprinters: Piezoelectric and thermal bioprinters. In the case of the former, a piezoelectric transducer, when an electric voltage is applied, contracts and causes shape distortion in the vibration plate which pushes the bioink droplet out of the printer nozzle. In case of the latter, a heater heats up the heat resistor generating an air bubble that again expands to push the droplet from the nozzle [3].

Advantages: [2]

• Speed: Inkjet bioprinters are known for their rapid printing speed, making them suitable for high-throughput applications.
• Multimaterial Printing: They are capable of printing multiple materials simultaneously, enabling the creation of complex tissue structures [3].
• Cost-Efficiency: Inkjet bioprinters are relatively cost-effective, making them accessible for research purposes.
• This technique also provides high resolution while also providing fast fabrication [4].?

Disadvantages:

• Lack of precision in droplet placement and size can impact the accuracy of fine details in tissue constructs [3].
• Cell Viability: The mechanical forces exerted during droplet ejection can damage fragile cells, affecting their viability2. Additionally, inkjet printers can only hold lower cell densities [4].
• Material Compatibility: Not all bioinks are suitable for inkjet printing, limiting the choice of materials for certain applications. The inks need to be of low viscosity because high-viscosity bioinks can lead to nozzle clogging [3].

Extrusion Bioprinters

Extrusion-based bioprinters utilize a syringe or a micronozzle to extrude bioinks onto a substrate, creating layered structures. This technique utilizes pneumatic or mechanical forces (piston or corkscrew) to pass the bioink through the printer nozzle into a design under computerized control.

Advantages: [3,4]

• Versatility: Extrusion bioprinters can handle a wide range of bioinks, including hydrogels, polymers, and cell suspensions, offering flexibility in material choices.
• Cost-Effective: These printers are often more cost-effective than their laser-based counterparts, making them accessible for research purposes.
• Cell density: Extrusion bioprinters can work with high cell densities.

Disadvantages: [3]

• Limited Speed: Extrusion-based systems tend to be slower than inkjet printers, which may be a drawback for large-scale production.
• Cell Damage: The mechanical pressure applied during extrusion can damage sensitive cells, affecting cell viability.
• Lower Resolution: This technique has a lower resolution compared to its alternatives.
• Extrusion bioprinting doesn’t do well with low-viscosity materials [4].

Laser-Assisted Bioprinters

Laser-based bioprinters use lasers to precisely pattern cells and biomaterials onto substrates. The laser-generated pulse, when focused at a specific point, causes the metal ribbon-associated bioink to form droplets which then fall onto the substrate in a set pattern.?

Advantages: [6]

• High Precision: Laser-based bioprinters offer exceptional precision and control, facilitating the creation of intricate tissue structures.
• Speed: They can print at high speeds, making them suitable for rapid prototyping and production.
• Minimal Cell Damage: Laser-based systems apply less mechanical stress to cells, preserving their viability [7].
• This technique completely eliminates the use of nozzles bypassing the issue of nozzle clogging making it a non-nozzle non-contact bioprinting technology.

Disadvantages:

• Costly: Laser-based bioprinters are often more expensive than other options, potentially limiting access for some researchers and institutions [6].
• Safety Concerns: Safety precautions are crucial due to the use of high-powered lasers, which can increase operational complexity.
• Contamination: The metal layer associated with the bioink is irradiated to create droplets. This, however, generates the risk of metal particle contamination.6

3D bioprinting represents a promising frontier in healthcare, regenerative medicine, and research. Each type of 3D bioprinter has its unique advantages and disadvantages, necessitating careful consideration when choosing the appropriate technology for specific applications. As the field continues to advance and address its challenges, it holds the potential to bring about groundbreaking changes in healthcare and personalized medicine. Simply put, with printed organs and medicines created just for you, the world of muggles is slowly but surely becoming more and more magical!

Written by Vishakha Kurlawala , Science Communicator, Nanomedicine Research Group, ICTMumbai

References:

1. Rider P, Ka?arevi? ?P, Alkildani S, Retnasingh S, Barbeck M. Bioprinting of tissue engineering scaffolds. Journal of Tissue Engineering. 2018;9:204173141880209. doi:https://doi.org/10.1177/2041731418802090
2. Bishop ES, Mostafa S, Pakvasa M, et al. 3-D bioprinting technologies in tissue engineering and regenerative medicine: Current and future trends. Genes & Diseases. 2017;4(4):185-195. doi:https://doi.org/10.1016/j.gendis.2017.10.002
3. Suntornnond R, An J, Chua CK. Bioprinting of Thermoresponsive Hydrogels for Next Generation Tissue Engineering: A Review. Macromolecular Materials and Engineering. 2016;302(1):1600266. doi:https://doi.org/10.1002/mame.201600266
4. Derakhshanfar S, Mbeleck R, Xu K, Zhang X, Zhong W, Xing M. 3D bioprinting for biomedical devices and tissue engineering: A review of recent trends and advances. Bioactive Materials. 2018;3(2):144-156. doi:https://doi.org/10.1016/j.bioactmat.2017.11.008
5. Li J, Chen M, Fan X, Zhou H. Recent advances in bioprinting techniques: approaches, applications and future prospects. Journal of Translational Medicine. 2016;14(1). doi:https://doi.org/10.1186/s12967-016-1028-0
6. Gruene M, Deiwick A, Koch L, et al. Laser Printing of Stem Cells for Biofabrication of Scaffold-Free Autologous Grafts. Tissue Engineering Part C: Methods. 2011;17(1):79-87. doi:https://doi.org/10.1089/ten.tec.2010.0359
7. What is a bioink? - Easy explanation. CELLINK. https://www.cellink.com/what-is-bioink/
8. Sigma Aldrich. 3D Bioprinting: Bioink Selection Guide. Merck. 2021;1(1). https://www.sigmaaldrich.com/IN/en/technical-documents/technical-article/cell-culture-and-cell-culture-analysis/3d-cell-culture/3d-bioprinting-bioinks
9. Gungor-Ozkerim PS, Inci I, Zhang YS, Khademhosseini A, Dokmeci MR. Bioinks for 3D bioprinting: an overview. Biomaterials science. 2018;6(5):915-946. doi:https://doi.org/10.1039/c7bm00765e?