Monday Article #6: 3D Bioprinting: A technology that could print tissues and organs?

Tanessri Muni

Do you know how many lives are lost every day waiting for an organ in the transplantation cube? And how many years of average do you think it takes to bring a drug from lab bench to market?

Current problems that we face in medical industry

The organ donation statistics reported by Health resources and services administration (HRSA) shows that there are almost 100,000 to 200,000 of men, women and children on the national transplant waiting list, and at least 17 people die each day due to end-stage organ failure, or die before an organ becomes available. This organ shortage crisis has deprived thousands of patients of a new and better quality of life and has caused a substantial increase in the cost of alternative medical care such as dialysis. Even though the patients undergo alternative treatments or medications, their life span and survival rate depends on how the body responds to medication. Besides that, there are limitations of only several patient responding well towards the treatment or medications as they have unacceptable side effects. These leads to the urgency of new drug development or repurposing. However, it takes an average of 12 years for an experimental drug to progress from bench to market, according to the US Food and Drug Administration (FDA). It is therefore, timely to consider how new technologies, namely functional genomics or the integration of technologies from the fields of engineering, specifically on biomaterials science can help to speed up drug development and make it more efficient.

3D Bioprinting and its application

• 3D Bioprinting, is a process of fabricating cell-laden bioinks into functional tissue constructs and organs from 3D digital models. It is an additive manufacturing process which is similar to 3D printing. However, instead of printing with plastics, 3D bioprinting prints with cells and biomaterials to create organ-like tissue structures.

• Given its potential to fabricate three-dimensional biomimetic functional tissue constructs, 3D Bioprinting has multi-fold application in the healthcare sector, including disease modelling, drug discovery and testing, high-throughput screening, and regenerative medicine.

• Though bioprinting of fully functional organs are still being researched more, considerable progress has been made to realize the greater goal of organ printing. Bioprinted tissues could be used as in vitro testing. Given the ethical concerns surrounding animal testing and the high cost involved, bioprinting is a viable alternate.

• In pharmaceutical research, bioprinting could be used as in vitro models for testing of drug efficacy, toxicity, chemotherapy or chemo-resistance to reduce the high cost and shorten the time of drug discovery.

Steps in 3D Bioprinting

The process follows a general outline in the form of three basic steps as shown in figure 1 and 2: Preparatory phase, Printing phase and Post-handling.

1. Preparatory phase is the designing of anatomically accurate 3D models via computer graphics software such as CAD/CAM and rendering it into stack of 2D layers of user-demarcated thickness which will be fed into the bioprinter for printing. This step also included the material or bio-ink selection.

2. The processing step involves the actual printing of the tissues by additive manufacturing techniques.

3. Post-processing refers to the maturation of the fabricated construct in a bioreaction and its structural and functional characterization.

Figure 1 shows the flow diagram for the process of 3D Bioprinting

Figure 2 shows the image flow diagram for the process of 3D Bioprinting

Advances in 3D Bioprinting techniques

Several kinds of additive manufacturing techniques have been developed for selective patterning of cells and biomaterials for fabrication of viable tissue constructs such as inkjet based 3D bioprinting, extrusion based 3D bioprinting, laser assisted 3D bioprinting, and stereolithographic based 3D bioprinting.

• Inkjet based 3D bioprinting, employs the use of bioink which forces out of a nozzle onto the substrate. This technique has already been effectively used for mammalian cell printing and patterning in addition to DNA and proteins.

• Extrusion based 3D bioprinting, can be done by Direct Ink Writing in which the apparatus continuously extrudes material out of the nozzle generating 3D architectures layer-by-layer. Researchers have encapsulated rodent hepatocytes in gelatin hydrogels in conjunction with alginate, chitosan and fibrinogen for fabrication of a functional liver.

• Laser assisted 3D bioprinting, utilizes pulsed laser beam in this process for deposition of bio-ink including cells onto a substrate. Utilization of laser for deposition of materials provides a non-contact direct writing process for 3D printing.

• Stereolithographic based 3D bioprinting, has been coordinated with clinical imaging techniques such as CT scan/MRI for improvement of diagnostic techniques, quality and design of prosthesis and implants and useful achievement of complex surgeries.

Why would these application be so revolutionary?

• With the technological advancement in the printing technique and development of efficient and cost-effective printing methods, it becomes necessary to regulate the quality control standard before transplantation in each step during the process, such as while designing a model, selection of bioink, printing validation, maturation of post-printing and assessment of product quality.

• Future developments in bioprinting is expected to witness rapid developments in bioprinters which can be readily deployed in hospitals. The bioprinters will be expected to perform bioprinting with high resolution, mechanical strengths and cell viability.

• Since the ultimate aim of bioprinting is to provide functional tissue constructs there is also need to develop better assays, which can analyze cell functionality in 3D constructs. Given the rapid pace at which bioprinting is emerging and the tremendous interest in this technology cutting across different scientific disciplines, it is expected that the above challenges could be overcome and bioprinted constructs will become available for translational studies as well as speed up the drug development process.

• It is expected that in the future, 3D Bio bioprinters can cheapen this expense and quicken testing time with better prediction of drug reaction and without waste money or time.

References

• Abouna G. M. (2008). Organ shortage crisis: problems and possible solutions. Transplantation proceedings, 40(1), 34–38. https://doi.org/10.1016/j.transproceed.2007.11.067.

• Agarwal, S., Saha, S., Balla, V. K., Pal, A., Barui, A., & Bodhak, S. (2020). Current Developments in 3D Bioprinting for Tissue and Organ Regeneration–a Review. Frontiers in Mechanical Engineering, 6, 90.

• Vijayavenkataraman, S., Yan, W. C., Lu, W. F., Wang, C. H., & Fuh, J. Y. H. (2018). 3D bioprinting of tissues and organs for regenerative medicine. Advanced drug delivery reviews, 132, 296-332.