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Written by: Christophe Pellisier
Written on: March 1st, 2014
Tags: biomedical engineering, health & medicine, material science
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About the Author
Christophe Pellisier is a student studying Biomedical engineering at USC as of 2014.
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Volume XVI Issue I > 3D Printed Organs
The field of tissue engineering has allowed developments in 3D printing organic parts and materials. 3D printing has become a widely popular means of manufacturing over the past decade, combining ease of design on a computer with fast production of custom parts. In regards to tissue engineering, these advantages have staggering implications in terms of their applications, potentially allowing completely new methods of treatment.
The field of tissue engineering has allowed developments in 3D printing organic parts and materials. 3D printing has become a widely popular means of manufacturing over the past decade, combining ease of design on a computer with fast production of custom parts. In regards to tissue engineering, these advantages have staggering implications in terms of their applications, potentially allowing completely new methods of treatment.

Introduction

The process of organ donation and transplant is a long and complicated one, requiring very exact matches between the donor and the recipient. As of August 2013, the national donor waiting list had more than 118,00 individuals waiting matches, a number which grows by approximately 300 people every month [1]. The ability to create organs that are identical matches by using cells derived from these patients would allow doctors and tissue engineers to save many lives. One way to do this is through 3D printing organs, a process that allows doctors to create organs from the intended recipient’s own cells.

Principles of Organic Printing

The science behind 3D printing organs got its start in the wider field of bio- printing, which, originally, closely resembled regular printing. The original bio- printer was, in fact, a modified inkjet printer with an ink cartridge filled with collagen, a protein found in connective tissues. The collagen molecules were deposited in a single layer onto a modified piece of paper, allowing scientists to print proteins in any shape they desired [1]. This basic principle of depositing layers of organic material has been adapted over the years, eventually allowing for 3D printing.
At its core, the process behind printing a 3-dimensional object is the same as printing a single 2-dimensional image. The main difference is that the final object is composed of multiple layers, each stacked on top of one another. To provide the structure for each layer, as well as for the completed organ, a biocompatible scaffold is used in many cases. This scaffold had enough space within it for the implanted cells to grow within and eventually dissolve as mature tissue fills in the blueprint that the scaffold specifies as shown in Fig. 1. In this way, each layer of the organ can be printed on the scaffold, similar to the concept of ink on paper [4].
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Figure 1: Example of the blueprint being created and filled.
Additionally,​ like different colors of ink, each layer is composed of several biological components that will eventually comprise the entire organ. Organs, by definition, are made up of multiple different types of tissue, each containing specific types of cells. Kidneys, for example, contain over 30 unique types of cells, and unless these cells are in their exact positions, the organ will not work [1]. In order to place the cells precisely, the printer contains a different cartridge and delivery needle for each cell type, which can alternate depending on the needs at the time.
All these aspects of the technology represent the current level to which scientists have developed the art of 3D printing organs. Moving forward, there are still many challenges to overcome, as well as technologies we must develop further, in order to reach the goal of printing organs customized for their intended recipients.

Advances and Challenges

Before we can say that the 3D printing of organs has been developed to a point being a commercially viable technology, scientists must first create several types of organs that can actually be implanted. Thus far, the only organs that have been successfully transplanted have been bladders [6]. In order to reach a point where other printed organs or constructs can be implanted, several other technologies must be developed.
The main reason that bladders have already been successfully printed and transplanted is because of the comparative simplicity of the organ. Bladders comprise two types of cells-urolithelial cells lining the exterior and interior, and smooth muscle cells providing a means to drain the organ by contraction [6]. Because of this, seeding the scaffold and getting the cells to grow properly is relatively simple compared to the challenge of predicting the growth and spread in the scaffold of the 30+ cell types present in a kidney. Each of these unique cell types grows differently in the scaffolding; printing must be very precise in terms of where the cells are placed. It is possible, however, that we will never be able to predict how tissues will grow to fill out the scaffold, so alternative printing methods are desirable for a few distinct reasons. You can find a visual of this in Fig. 2 .
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Figure 2: A researcher dips a bladder-shaped mold, seeded with human bladder cells, into a growth solution. Brian Walker (AP).
Since the scaffolding is initially composed of a material like collagen that would not normally be found in the organ, it carries a risk of rejection [1,6]. Although it does degrade over time, this potential rejection coupled with the difficulty of predicting the growth of multiple types of cells in it means we should look into alternative ways of printing (See Fig. 3) . One promising technique that several groups have begun researching involves printing without the scaffold, instead relying on what are referred to as tissue spheroids for structure.
Printing with tissue spheroids is best likened to inkjet printing, wherein tiny droplets of ink are deposited on the substrate that you are printing on. In 3D organ printing, those droplets are clusters of cells mixed with some amount of growth nutrient, but there is the possibility of different inks mixing for undesirable results [2]. To prevent this, each group of spheroids, collectively known as a cell aggregate, is encapsulated in a hydrogel mold [4]. This hydrogel mold does not serve the same function as a traditional scaffold, as rather than providing mechanical stability, it provides a barrier that allows for the cell aggregates to fuse into tissues without combining. This technique would allow for printing of entire organs without the use of scaffolds, as well as a higher degree of control over how the tissues develop [3].
Some labs have already begun to experiment with this technology, and recently have been able to print vascular tissue without using scaffolding. Rather, the printer lays down layer-by-layer of these spheroids in droplet-sized portions, allowing the individual droplets to grow and fuse together, forming an aggregate [5]. In the case of printing a vascular tissue such as an artery, two concentric rings would be printed on each layer, separated by a layer of hydrogel. One ring would be comprised of endothelial cells that would make up the inner lining of the vessel, and the other ring would be comprised of smooth muscles. The individual droplets comprising each ring fuse over time, forming solid tubes of cells, before eventually the hydrogel is removed, leaving an intact vascular construct [3]. This technology of utilizing tissue spheroids to print complete organs is still years from perfection; however, although in its current state it represent a significant level of technological development in the field of tissue engineering.
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Figure 3: Scaffolding by the printing process can create stuctures for organs as shown here.

Conclusion

While the technology today is capable of replacing some organs in patients, tissue engineering still has a long way to go in the field of 3D printing organs. As the technology continues to develop, however, we can expect to see advances in how we treat patients suffering from organ failure, and hopefully someday we will be able to prevent many deaths from such diseases.

References

    • [1] S. Leckart. “How 3-D Printing Body Parts Will Revolutionize Medicine” Popular Science 6 August, 2013. http://www.popsci.co​m/science/article/20​13-07/how-3-dprintin​g-body-parts-will-re​volutionize-medicine​
    • [2] I.T. Ozbolat. “3D Functional Organ Printing: Promises and Future Challenges” Proceedings of 2013 Industrial and Systems Engineering Research Conference 2013. Print.
    • [3] V. Mironov. “Organ Printing: computer-aided jet-based 3D tissue engineering” Trends in Biotechnology Vol. 21, No.4, 4 April 2003. http://www.sciencedi​rect.com.libproxy.us​c.edu/science/articl​e/pii/S0167779903000​3 37
    • [4] T. Boland. “Cell and Organ Printing 2: Fusion of Cell Aggregates in ThreeDimensional Gels” The Anatomical Record Part A 272A:497–502, 2003. http://onlinelibrary​.wiley.com/doi/10.10​02/ar.a.10059/pdf
    • [5] V. Mironov. “Organ printing: Tissue spheroids as building blocks” Biomaterials 30(12):2164-2174, April 2009. http://www.ncbi.nlm.​nih.gov/pmc/articles​/PMC3773699/
    • [6] A. Atala. “Tissue-engineered​ autologous bladders for patients needing cystoplasty” The Lancet, Vol. 367, 9518:1241-1246, 15-21 April 2006. http://www.sciencedi​rect.com.libproxy.us​c.edu/science/articl​e/pii/S0140673606684​389
    • [7] https://www.youtube.​com/watch?v=N5xQB7Rg​d98
    • [8] http://www.washingto​npost.com/wp-srv/spe​cial/science/how-bio​printing-works/
    • [9] http://www.patheos.c​om/blogs/godandthema​chine/2012/06/printi​ng-a-humanbladder-an​d-kidney/