3D bioprinting is evolving rapidly since researchers have innovated and driven the field forward. However, as a technology, 3D printing is not a new invention. The first steps in 3D printing were taken in 1980s, when in 1984 Charles Hull filed a patent for the first commercial 3D printing technology. This has been a symbol of the birth of 3D printing, and it created the base for 3D bioprinting as well. Bioprinting came into picture in 1988, when Robert J. Klebe used inkjet printer for printing cells.1 After these first steps, the field has constantly evolved, and new methods and techniques have been discovered. The countless possibilities and opportunities to create something ground-breaking keep intriguing scientists, and thus bioprinting has become a popular technology.
What is 3D bioprinting?
3D bioprinting is a technology where bioinks, mixed with living cells, are printed in 3D to construct natural tissue-like three-dimensional structures. Currently, this technology can be used in various research areas, such as tissue engineering and new drug development.
What is 3D bioprinting and how does bioprinting work?
3D bioprinting is an additive manufacturing process that uses bioinks to print living cells developing structures layer-by-layer which imitate the behavior and structures of natural tissues. Bioinks, that are used as a material in bioprinting, are made of natural or synthetic biomaterials that can be mixed with living cells.
The technology and bioprinted structures enable researchers to study functions of the human body in vitro. 3D bioprinted structures are more biologically relevant compared to in vitro studies performed in 2D.
Mostly, 3D bioprinting can be used for several biological applications in the fields of tissue engineering, bioengineering and materials science. The technology is also increasingly used for pharmaceutical development and drug validation. Clinical settings such as 3D printed skin and bone grafts, implants and even full 3D printed organs are currently at the center of bioprinting research.
3D bioprinting of tissues and organs for regenerative medicine
Three-dimensional bioprinting plays an important role in tissue engineering which aims to fabricate functional tissue for applications in regenerative medicine and drug testing. Tissue regeneration and reconstruction could enable the possibility to repair or replace damaged tissues and organs.
Advantages and disadvantages of 3D bioprinting
Advantages of 3D bioprinting
- Allows mimicking the real structure of desired tissue/organ etc.
- Possibility to revolutionize future medical treatment capabilities
- Possible creation of patient-specific and organ-specific treatments
- Effects of drugs can be examined more accurately
- Decreases animal testing
- Biocompatibility with human cells and tissues
- Automating complex processes
- Consistency, less human errors
Disadvantages of 3D bioprinting
- Pricing, expensive technology
- Complexity
- Maintaining cell environment can be difficult
- Ethical concerns
- Energy consumption
3D bioprinting bioinks
Bioinks are used as the base material when bioprinting tissue-, organ-, or bone-like structures with bioprinters. 3D bioinks can be cell-laden, scaffold-free, or cell-free, like GrowInk™, which is an easily customizable hydrogel-based bioink made of nanofibrillar cellulose and water.
GrowInk’s cell-free form allows it to be tailored well to fit multiple research areas and purposes.
Choosing the right composition of bioink, and the bioink density can affect the cell viability and cell density, hence, selecting the most suitable bioink for each research purpose is essential.
3D bioprinters
3D printers and 3D bioprinters are similar to each other, but 3D printers are designed to print solid materials, where 3D bioprinters are designed to print liquid or gel. 3D bioprinters are also designed to handle sensitive material that contain living cells, without creating too much damage on the end result. Bioprinters can be inkjet based, laser assisted, or extrusion based. Each printer type has its pros and cons when it comes to cost, cell viability, cell density, resolution, and so on. Bioprinters’ compatibility with bioinks also varies, and therefore it is important to ensure the bioprinter and bioink work well together.
Commercially available cell printers
| Company | Instrument |
|---|---|
| 3D biopriting solutions | Fabion |
| 3D cultures | Tissue Scribe |
| Advanced Solutions | BioAssemblyBot |
| Allevi3D | Allevi |
| Aspect Biosystems | RX |
| Bioprinting solutions | Brinter |
| CellInk | Inkredibe, Bio X |
| Digilab | CellJet |
| Envision Tec | 3D-bioplotter |
| Felix Printers | FELIX Bioprinter |
| Fluicell | Biopixlar |
| GeSim | BioScaffolder |
| Inventia | Rastrum |
| Organovo | NovoGen |
| Poietis | NGB-R |
| Regemat3D | Bio V1 |
| RegenHU | R-Gen |
| Rokit | Dr Invivo 4D |
| Shibuya Kogyo / Cyfuse | Regenova |
| SunP Biotech | BioMaker, Alpha |
| Tissuelabs | TissueStart |
| WeBio | WeBio |
3D Bioprinting solutions – hints and tips for bioprinting
- Select the most suitable bioink for your research purpose and ensure the bioink you are using is compatible with the selected printing method and cell types
- Know what you are printing – create a new digital 3D model of the structure you want to print or get a license for an existing model
- Use fresh or new printer tips that are specifically fitted for your system
- Test different nozzle/needle sizes, printing speeds, and layer heights and optimize them based on the results
- Make sure the working temperature is suitable for the printer and the used materials
- Set an optimal printing pressure. A bit higher pressure is usually needed when printing with cells
Future of 3D bioprinting
The rapid development of technology can also be seen in the advancement of bioprinting. Three-dimensional bioprinting technology has the potential to solve numerous problems in areas such as healthcare. Functioning bladders, which have been grown using bioprinted tissue from patients’ own cells have already been transplanted into human body successfully2,3. Researchers are constantly researching the possibility of bioprinting other functioning organs.
One future scenario of 3D bioprinting could be that no-more organ donors are needed, as personalized human organs can be printed using the patients’ own cells or stem cells as a base. This technology can be revolutionizing in preventing and fixing diseases. Eventually, it is hoped that bioprinting technology will enhance medical care and make it more efficient.
Bioprinting publications
Wang, Q., et al., (2021). Rheological and Printability Assessments on Biomaterial Inks of Nanocellulose/Photo-Crosslinkable Biopolymer in Light-Aided 3D Printing. Available from: https://doi.org/10.3389/fceng.2021.723429.
Fonseca, A.C., et al., (2020). Emulating Human Tissues and Organs: A Bioprinting Perspective Toward Personalized Medicine. Chemical Reviews. Available from: https://doi.org/10.1021/acs.chemrev.0c00342.
Wang, X., Q. Wang, and C. Xu, (2020). Nanocellulose-Based Inks for 3D Bioprinting: Key Aspects in Research Development and Challenging Perspectives in Applications-A Mini Review. Bioengineering (Basel), 7(2). Available from: https://doi.org/10.3390/bioengineering7020040
Yadav, C., et al., (2020). Plant-based nanocellulose: A review of routine and recent preparation methods with current progress in its applications as rheology modifier and 3D bioprinting. International Journal of Biological Macromolecules. Available from: http://www.sciencedirect.com/science/article/pii/S0141813020349631.
Ashammakhi, N., et al., (2019). Bioinks and bioprinting technologies to make heterogeneous and biomimetic tissue constructs. Materials Today Bio, 1: p. 100008. Available from: https://www.sciencedirect.com/science/article/pii/S2590006419300146.
Di Marzio, N., et al., (2020). Bio-Fabrication: Convergence of 3D Bioprinting and Nano-Biomaterials in Tissue Engineering and Regenerative Medicine. Frontiers in Bioengineering and Biotechnology, 8(326). Available from: https://www.frontiersin.org/article/10.3389/fbioe.2020.00326.
Jovic, T.H., et al., (2019). Plant-Derived Biomaterials: A Review of 3D Bioprinting and Biomedical Applications. Frontiers in Mechanical Engineering, 5(19). Available from: https://www.frontiersin.org/article/10.3389/fmech.2019.00019.
References
1Gu, Z., Fu, J., Lin, H. and He, Y., 2020. Development of 3D bioprinting: From printing methods to biomedical applications. Asian Journal of Pharmaceutical Sciences, 15(5), pp.529-557.
2Atala, A., Bauer, S., Soker, S., Yoo, J. and Retik, A., 2006. Tissue-engineered autologous bladders for patients needing cystoplasty. The Lancet, 367(9518), pp.1241-1246.
3 Belton, P., 2018. 'A new bladder made from my cells gave me my life back'. BBC, [online] Available at: <https://www.bbc.com/news/business-45470799> [Accessed 6 August 2021].