Impact of 3D Bioprinting of Organs

Translation Report

Biomedical Engineering

Prepared by Kaisei Tokita

October 2019

Figure 1: Fabrication of tissue structure

Source: https://medium.com/@shadabhassan/the-feasibility-of-3d-bioprinting-2bc1d434222f

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Table of Contents

Introduction...................................................................................................................................... 1

Applications...................................................................................................................................... 3

Obstacles.......................................................................................................................................... 5

Conclusion........................................................................................................................................ 6

Table of FiguresFigure 1: Fabrication of Tissue Structure.......................................................................................... 1

Figure 2: Variations of bioink categories and possible products.......................................... 1

Figure 3: Different methods of bioprinting.......................................................................... 2

Figure 4: Process of 3D Bioprinting...................................................................................... 3

Figure 5: Process of 3D bioprinting skin............................................................................... 4

Figure 6: Challenges within printing of organs..................................................................... 5

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Introduction

The impact of 3D bioprinting will revolutionize the healthcare industry and bolster research of a vast range of products and treatments. With the growing need for organ donations and advancements in medicine needing testing upon representative models, the possibilities for bioprinted organs are immense. 3D bioprinting is the process of fabricating functional tissues and organs from a 3D model with material containing cells [1 regen]. The deposited material is called bioink, a material that provides the architectural structure and the environment for the cells to mature [2 progress tissue]. Different types of bioink present strengths and weaknesses for varying fabrications. Bioinks are acquired with varying levels of difficulty and have influential impact to their possible implementation. Bioinks are naturally and synthetically sourced, presenting differences that determine their use case.

Figure 5: Variations of bioink categories and possible products

Source: Adapted from [4]

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The process of bioprinting includes pre-processing, processing, and post-processing. Within pre-processing, the tissue or organ of issue is imaged with methods such as CT scans and ultrasound. Next, the desired print is modeled with CAD (computer-aided design) software and typically presented in .stl (stereolithography) format due to its large range of compatibility. The processing stage involves the actual printing of the models.

The main styles of printing are laser-based, extrusion-based, droplet-based, and stereolithography. Laser-based printing uses a high-powered laser that directs energy onto a layer of bioink in the directed pattern creating a print without any contact. Extrusion-based printing pushes bioink and cell laden layers out onto a surface in a desired pattern, showing promise to printing organs due to its scalability and speed as the most popular method. Droplet-based printing is based on inkjet printers commonly found today, ejecting material in the form of droplets following a pattern. Stereolithography printing uses UV light that cures a layer of sensitive resin and the 3D shape forms as more layers are cured in the vertical direction, producing the highest quality prints of all methods.[1]

Figure 6: Different methods of bioprinting

Source: Adapted from [2]

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The post-processing stage comprises of putting the finished print into an environment for the cells to further bond and maturate. Different environments such as incubators or sterile environments are required based on the cells used during the print. Once this is complete, the printed tissues/organs are ready to be used in vitro as materials to be tested on for research or transplanted into a patient.

Applications

The development of this technology promises to provide aide to the fabrication of organs for transplant as well as research. Efforts to bioprint skin tissue have been pursued for transplant and research. This would allow for skin grafts to be applied onto wounds to provide a natural barrier for the wound to heal [3 skin tissue]. There are cosmetic opportunities with this development for individuals looking to change their appearance in a much more natural manner and provides an option for burn victims. Advancements in research can be made with readily available realistic human skin tissue for testing. The engineered skin can show the effects of drugs through the skin as well as provide substance with which to better understand skin diseases and develop new drugs to combat such issues [3]. Hydrogels are the main bioink commonly used for skin tissue printing because they contain mainly collagen at about 70% of the protein in the skin [3]. The basic model of skin tissue fabrications is a double layered structure with dermis and epidermis [4 novel]. Laser assisted printing is the most common approach with this organ but does not have the highest rate of viability during post-processing [3]. While this method produces high resolutions and higher cell densities, there is limited understanding on the effects of the laser exposure on the cells [3]. It will need to be further investigated for the possibility of skin grafts to ensure the safety and health of its recipient [3].

Figure 7: Process of 3D Bioprinting

Source: [1]

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Another area for application is the development of fabricating a liver. Given the wide array of functions the liver serves from digesting fats to detoxifying and metabolizing drugs, liver disease and failure cases are growing [1]. Often the most effective treatment for these diseases is to have a full liver transplant once the liver loses its regenerative values rather than treat it in hopes of recovery. [1]. Fabricating liver tissues would also allow researchers to test and examine the effects of drugs on diseases liver cirrhosis and hepatocellular carcinoma to better improve their effects and limit negative effects [2]. The need for livers is vastly increasing and this technology promises to aid with this lingering issue.

Obstacles

Figure 5: Process of 3D bioprinting skin

Source: doi: 10.1186/s41038-017-0104-x

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There are many barriers to this technology truly breaking through to mainstream usage by hospitals and patients. One issue is the cost of fabricating organs in this manner. The upfront work on equipment and time needed to ensure equipment is working properly can be a large task. In an interview with Colleen Richards, a graduate student at Cal Poly, she exclaimed that the largest issue she faced with managing a bioprinter on campus was the troubleshooting and maintenance. Most of her time was spent calibrating the machine as it would fail to move the extrusion needle properly or the pressure that material was being deposited was incorrect. She also struggled with the costs of materials and bioink to use in projects, producing a significant pressure on her work and the availability of resources. There are also issues with the fabrications themselves as they are not naturally created and lack the complexity or the strength of original organs. While this technology presents a viable alternative to current methods of patient care and research, it needs further development to become a reasonable method for the public.

Figure 6: Challenges within printing of organs

Source: Adapted from [4]

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ConclusionThe developing field of 3D bioprinting presents a new solution to issues within healthcare and within research, but currently is not entirely structured. As new methods of development of materials arise and resolution of printers increase there are greater improvements possible to the quality of prints and their viability to replace original human organs. While the technology is not fully developed yet, the field is expanding and promises to fix great issues ailing patients worldwide.

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Works Cited

[1] S. Vijayavenkataraman et al., “3D Bioprinting of tissues and organs for regenerative medicine,” Advanced Drug Delivery Reviews, vol. 132, p. 296-332, July 2018. [Online]. Available: Science Direct, DOI: 10.1126/sciadv.aaw2459. [Accessed: October 21, 2019].

[2] I. Matai et al., “Progress in 3D bioprinting technology for tissue/organ regenerative engineering,” Biomaterials, vol. 226, p. 1-32, January 2020. [Online]. Available: Science Direct, DOI: 10.1016/j.biomaterials.2019.119536. [Accessed: October 21, 2019].

[3] W. Yan et al., “3D bioprinting of skin tissue: From pre-processing to final product evaluation,” Advanced Drug Delivery Reviews, vol. 132, p. 270-295, July 2018. [Online]. Available: Science Direct, DOI: 10.1016/j.addr.2018.07.016. [Accessed: October 21, 2019].

[4] B. Zhang et al., “3D Bioprinting: A Novel Avenue for Manufacturing Tissues and Organs,” Engineering, vol. 5, p. 777-794, August 2019. [Online]. Available: Science Direct, DOI: 10.1016/j.eng.2019.03.009. [Accessed: October 26, 2019].

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Figures Cited

[1] “The Feasibility of 3D Bioprinting,” Medium, 2017. [Online]. Available: https://medium.com/@shadabhassan/the-feasibility-of-3d-bioprinting-2bc1d434222f. [Accessed: October 28, 2019].

[4] S. Vijayavenkataraman et al., “3D Bioprinting of tissues and organs for regenerative medicine,” Advanced Drug Delivery Reviews, vol. 132, p. 296-332, July 2018. [Online]. Available: Science Direct, DOI: 10.1126/sciadv.aaw2459.

[5] P. He et al., “Bioprinting of skin constructs for wound heal,” Burns Trauma, BioMed Central, January 2018. [Online].

Available: Science Direct, doi: 10.1186/s41038-017-0104-x. [Accessed: October 25, 2019].