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Abstract: 3D bioprinting is a new generation technology that was first demonstrated in the 1980s, rapidly growing as scientists drive through this field. This is an advanced level of tissue engineering and regenerative medicine research. 3D bioprinting is a technology where a suitable ink known as bio-ink is used to print an organ layer by layer on a predesigned tissue scaffold. This interdisciplinary technology includes biology, medicine, mechanical engineering, and material science. The present utilization of this technology is first to exploit it for organ transplantation deficit, as this is far too optimistic to talk about now due to the complexity of human organs. Secondly, traditional methods like 2D cell culture and animal experiments for drug delivery techniques and drug screening are far more complex than in a 2D environment. 3D bioprinting has become the perfect approach to solve these upfront issues. This revolutionary innovation in the clinical field now becomes the initiator of the personalized medicine era.
Introduction:
3D Bioprinting is a novel technology to print any organ or specific human organs and tissues using bio-inks and biomaterials. This is an advanced level in tissue engineering and regenerative medicine. This game-changing technique can eradicate the organ transplantation waiting time forever.
According to the statistics, 17 people die each day waiting for an organ transplant in India. And about 106,363 men, women, and children are on the waiting list of the national transplantation network. Every patient is waiting for a suitable organ donor for their successful transplantation. 3D bioprinting can be the most brutal way to put a full stop to all organ shortage problems faced worldwide. Many models of 3D printed organs have been published like heart, ear, kidney, liver, etc. The University of Korea and Asan medical center have successfully 3D printed a device that can keep liver patients alive. The SRM University Chennai, India, has grown an ear on a 3D printed scaffold [1].
3D bioprinting is based on three approaches
1. Bio-mimicry,
2. Autonomous self-assembly,
3. Mini tissue building blocks.
Bioprinting utilizes cells and cell factors as bio-ink to fabricate the necessary structure. Scaffolds are one of the key elements for tissue regeneration as it gives the essential support and physical form for the cells.[1]
Fig 1: 3D bioprinting technologies explained. (Source: Merck)
The parameter that needs to be considered while fabricating scaffolds and bio-inks is the Biocompatibility of biomaterials. The scaffold material must accommodate encapsulated cells and the recipient’s body. Thus the bio-printed organ or implant should be cytocompatible and histo-compatible [2],[3].
Hydrogels are an attractive material for bioprinting as they have very low viscosity and their basic structure of 3D cross-linking of polymer chain containing water mass. Next comes the porosity, volume and geometry, and the behavior of cells after adhesion into a scaffold. Different pore sizes can affect the mobility of substances from implants to other cells and lead to poor extracellular matrix development. It can also hinder oxygen and nutrient transport. Hence, pore size and interconnectivity are significant. Mechanical strength and high elastic molecules are implanted in-situ. They produce stress shielding and can stop new bone formation [3].
Fig 2: Core fabrication technique of 3D bioprinting.
The frequently utilized techniques for bioprinting include
1. Ink-jet based bioprinting:
It is a non-contact printing process that deposits precise droplet (Pico liter) of bio-ink onto a hydrogel substrate-based under computer control. The standard method used is thermal ink-jet technology, where ink drops are created by the heating method so that the inflated bubble forces the ink out of the narrow nozzle onto the substrate [4].
2. Pressure assisted bioprinting:
This technique is based on the extrusion of bio-ink out of the nozzle to create 3D printed structures. This technique is advantageous as it can be processed at room temperature, direct incorporation of cells, and homogenous distribution of cells.
3. Laser-assisted bioprinting (LAB):
As the name suggests, it uses a laser as the energy source to deposit biomaterial onto a scaffold. LAB mainly uses Nano-second lasers with UV or near UV wavelengths as energy sources to print hydrogels, cells, or even proteins. Researchers have used laser-assisted bioprinting technology to print cells. Example: Human dermal fibroblasts, bovine pulmonary artery endothelial cells.
4. Stereolithography:
It is a technology of solid freedom, nozzle-free technology developed in the late 1980s. A photo-sensitive polymer liquid is solidified upon illumination. This technology uses digital micromirror arrays as controllers to polymerize light-sensitive polymer materials.
Software in bioprinting:
Every 3D bioprinting starts with 3D modeling generated on a computer. This computational part is highly crucial. Most of the existing software is Graphical User Interface (GUI) based control system. CELLINK designed their software package named Heartose, DNA cloud, and DNA studio for fast droplets layer by layer printing. Allevi developed the software called Allevi Bio Print Protocol software which runs online and can work from any computer. Digilab Company has developed cell jet printers and windows based software for printers. Nonetheless, software development still lags behind the advancement of bioprinting. Generally, the model creation for bioprinting is CAD software and STL format [5].
Major – challenges:
The narrow range of printable Biomaterial available.
Human tissues and organs are complex physiologically and structurally. So it is impossible to use one as biomaterial throughout.
There is an increasing need for advanced printing techniques and printers with primary biocompatible and cytocompatible materials.
Bio–ink should not cause any side effects.
The products developed using 3D bioprinting should be eco-friendly and should support the proliferation of cells, and should be able to give the space for the growth of cells.
In the future, the research focus will include the Development of 3D bioprinting techniques with better bio compatible materials and greater printability. Overall, an improvement of biological characteristics of material [6],[7].
Conclusion:
At present, 3D bio-printed organs are not ready for transplant. Still, with expansion and better development of bio printable material, it will eventually become a revolutionary change in drug delivery assessing methods in healthcare and regenerative medicine. Over the last decades, 3D bioprinting has been widely applied in constructing many tissues and organs. This technology will become a vital role in the rise of personalized medicine.
References:
1. Gu Z, Fu J, Lin H, He Y. Development of 3D bioprinting : From printing methods to biomedical applications. Asian J Pharm Sci. 2020;15(5):529-557. doi:10.1016/j.ajps.2019.11.003
2. Kačarevi´kačarevi´c ŽP, Rider PM, Alkildani S, et al. materials An Introduction to 3D Bioprinting: Possibilities, Challenges, and Future Aspects. doi:10.3390/ma11112199
3. Vijayavenkataraman S, Yan WC, Lu WF, Wang CH, Fuh JYH. 3D bioprinting of tissues and organs for regenerative medicine. Adv Drug Deliv Rev. 2018;132:296-332. doi:10.1016/J.ADDR.2018.07.004
4. Science B. Bio inks for 3D Bioprinting : An Overview. Published online 2017.
5. Pakhomova C, Popov D, Maltsev E, Akhatov I, Pasko A. Software for bioprinting. Int J Bioprinting. 2020;6(3):41-61. doi:10.18063/IJB.V6I3.279
6. Agarwal S, Saha S, Balla VK, Pal A, Barui A, Bodhak S. Current Developments in 3D Bioprinting for Tissue and Organ Regeneration-A Review. doi:10.3389/fmech.2020.589171
7. Murphy S V, Atala A. 3D bioprinting of tissues and organs. Nat Biotechnol 2014 328. 2014;32(8):773-785. doi:10.1038/nbt.2958
About the Author
Author : Arunaa NG
Bio: A biotech enthusiast, a passionate reader and writer, ever ready to take up challenges and interested in neuroscience, behavioural science, genetics and molecular biology, an aspiring researcher in the field of medicine and science.
Editor: Aarushi Chitkara
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