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Organ Printing: A Dream Coming True?
#1
This is post no. 1 under the main topic.
A Printed Liver?

A press release issued in April 2013, by Organovo Holdings, Inc., USA, a manufacturer of 3D human tissues, announces the creation of a three dimensional human liver tissue using a technology called “bioprinting”.

These tissues were engineered using a bioprinting platform branded “NovoGen by the Organovo. As Dr. Sharon Presnell, Chief Technology Officer and Executive Vice President of Research and Development, at Organovo has stated in the press release; “They actually look and feel like living tissues."

The printed liver tissues which are comprised of about 20 cell layers, successfully imitate the characteristic cellular patterns of the natural liver tissues. Furthermore, these tissues could carry out essential liver functions such as production of albumin, fibrinogen and transferrin, inducible enzyme activities etc. Organovo claims that their bioprinted liver tissues were even capable of carrying out Cholesterol biosynthesis, which has not previously shown feasible in vitro in a multi-cellular 3D human liver system.

[Image: organovo-liver-tissue-model-1.jpg]
A stained Cross-section of the human liver tissue bioprinted by Organovo

Bioprinting- An Introduction

Bioprinting is a process essentially similar in principle to the digital 3D printing technology. Instead of ink droplets or materials like plastic or metal, the printer heads of these “bioprinters” deposit several layers of cellular aggregates-termed as “bioink”- along with a cell-free dissolvable supporting medium-termed as “bio-paper’-in both horizontal and vertical directions, creating a three-dimensional cellular organ.

Bioink

Bioink particles are the building blocks of the bioprinting process. These bioink units are masses of cells of either spherical or cylindrical shapes. These can be composed of a single cell type (homogenous) or of different types of cells (heterogeneous). Bioink can be prepared using several methods. One such method involves culturing cells in an appropriate medium followed by centrifuging into pellets. These pellets are then transferred into micropipettes and incubated in order to re-establish the cellular interactions. Finally, these cell pellets are extruded into cylindrical bioink particles. Alternatively, these extruded cylinders can be cut into fragments of uniform size and placed overnight in a gyratory shaker allowing them to be shaped into spherical bioink droplets.
The type of cells in the bioink depends upon the type of tissue to be printed. A bioprinter can also carry different kinds of bioinks in different cartridges in the same way a conventional printer contains inks of different colours.

Bio-paper

Bio-paper-a support matrix usually composed of biocompatible hydrogel- acts as the framework and protects the cells during the printing process. However, this is different from the traditional solid scaffold-based tissue engineering, where cells are seeded into a natural or synthetic scaffold followed by culturing in a bioreactor. In the bioprinting process, the bio-paper is ultimately removed, thus making the printed organ ‘scaffold-free’, implying that it does not depend on the scaffold for its three-dimensionality. The hydrogel particle may also be used to as gap-fillers in the printing process to create the hollows and grooves within organs where necessary.

Bioprinting- The Process

In the process of printing the tissue, ‘an image’ i.e. a computer-based model of the target tissue has to be first created. Then, the bioink particles required for printing have to be developed using a suitable protocol. The types of bioink are determined based on the type tissue that is to be printed. For example, for the printing of the liver tissue, three main types of cells found natural liver tissues-namely hepatocytes, endothelial cells and hepatic stellate cells- were used as bioinks. Then these bioinks are loaded into the bioprinter along with the bio-paper. The cell aggregates and the supporting hydrogel matrix are deposited layer-by-layer as directed by the digital design. After the printing process is completed the cells-by themselves-rearrange and fuse into a functioning tissue. This self-assembling, which is entirely a natural phenomenon, increases the efficiency of the bioprinting by making it sufficient to deposit the bioink particles roughly at the required position without having to print all the intricate details of the natural tissue. After the post–printing assembly has taken place, the tissue is further matured in an incubator. The supporting gel matrix is either dissolved away or removed by some other means.

[Image: bioprinting_stages.jpg]

Layer-by-layer approach of bioprinting Image source: http://www.explainingthefuture.com/bioprinting.html

Bioprinting-The Advantages

Since the printed tissues are scaffold-free, they eliminate the risk inducing of immunogenic reactions which are common with other engineered tissues. There is the possibility of manufacturing bioink particles using the cells of the recipient, thus making them better candidates in organ transplanting. Bioprinting enables the creation of complex organs composed of multiple cell types with vascular architecture. Furthermore, bioprinting is an automated process making the fabrication of engineered tissues reproducible, scalable and economical.

Bioprinting- The Future Promises

With the ultimate goal of printing a complete, functioning human organ that can be used in organ transplant, scientists are envisioning an array of possibilities bioprinting will bring about. One of the proposed uses is to fabricate tissues that are to be used as models in drug testing and development. Rather than the currently used animal models or the two dimensional cell cultures, these 3D organs will provide better models for such experiments since they closely resemble the natural tissues in their structure and functionality. There is also hope of using this technology in the fields of regenerative medicine. Cosmetics is also another prospective area which will benefit from the bioprinting technology. Moreover, there is the prospect of developin in-situ bioprinting that will enable tissue regeneration by directly depositing the bioink on the body of the patient. Studies are also ongoing about manufacturing food products such as artificial raw meat using the bioprinting technique.

[Image: skin_printer_500x282.jpg]

In-situ bioprinting Image source: http://www.explainingthefuture.com/bioprinting.html

[Image: face_printer_550x203.jpg]

Bioprinting in Cosmetics Applications Image source: http://www.explainingthefuture.com/bioprinting.html

Sources

1.Jakab, K., Norotte, C., Marga, F., Murphy, K., Vunjak-Novakovic, G., & Forgacs, G. (2010). Tissue engineering by self-assembly and bio-printing of living cells. Biofabrication, 2(2), 022001.

2.Marga, F., Jakab, K., Khatiwala, C., Shepherd, B., Dorfman, S., Hubbard, B., ... & Gabor, F. (2012). Toward engineering functional organ modules by additive manufacturing. Biofabrication, 4(2), 022001.

3.http://ir.organovo.com/news/press-releases/press-releases-details/2013/Organovo-Describes-First-Fully-Cellular-3D-Bioprinted-Liver-Tissue/default.aspx

The following videos will provide a better understanding of the bioprinting process and its applications:










Reference:
http://www.organovo.com/3d-human-tissues...issue-mode
 
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#2
This is post no. 2 under the main topic.
Some labs and private companies have already taken the first steps by using 3D-printing technology to build tiny chunks of organs.

Regenerative medicine has already implanted lab-grown skin, tracheas and bladders into patients, body parts grown slowly through a combination of artificial scaffolds and living human cells. By comparison printing technology offers both greater speed and computer guided precision in printing living cells. The ultimate goal is to make replacement skin, body parts and eventually organs such as hearts, livers and kidneys.

There are four levels of complexity in building organs with 3D printing. Skin and similar flat structures with mostly one type of cell represent the easiest organs so they are in first group. In second group we can put blood vessels and any other structures with two major cell types. After this two follow more difficult third level. This group includes hollow organs such as the stomach or bladder every with more complicated functions and interactions with other organs. Most complicated organs with main role such as heart, liver or kidneys are members of fourth level and they represent ultimate goal for bioprinting.

Scientists previously built lab grown organs by creating artificial scaffolds and seeding the scaffold with living cells. The technique they used for grow was first implanted in patients in 1999. Last decade they were busy with building 3D printers that can at the same time print both an artificial scaffold and living cells. Some other labs and scientists think they can bypass the artificial scaffolds by harnessing living cells tendencies to self organize. Scientists have experimented with building tiny slices of livers by first creating "building blocks" with the necessary cells. Then they can situate the building blocks in layers that allow the living cells to start growing together. Stem cells taken from a patient's fat or bone marrow can provide the material for making an organ that the body won't reject.
Sasa Milosevic
 
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#3
This is post no. 3 under the main topic.
Soon we can have organic living space ships perhaps that we can use to get around in. Sounds quite fun if we can print body parts and rejuvenate we could find more interesting scenery and more interesting genetics out there.

Oh no I am starting to sound like an alien traveler already watch out multi-verse here we come.
 
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