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[[File:Printer 3D Bioprinting Solutions.jpg|thumb|Three-dimensional bioprinter developed by the Russian company, 3D Bioprinting Solutions.]]
[[File:Printer 3D Bioprinting Solutions.jpg|thumb|Three-dimensional bioprinter developed by the Russian company, 3D Bioprinting Solutions.]]


A '''printable organ''' is an [[artificial organ|artificially constructed]] device designed for organ replacement, produced using [[3D printing]] techniques. The primary purpose of printable organs is in [[organ transplantation|transplantation]]. Research is currently being conducted on artificial [[heart]], [[kidney]], and [[liver]] structures, as well as other major organs. For more complicated organs, such as the heart, smaller constructs such as [[heart valve]]s have also been the subject of research. Some printed organs have already reached clinical implementation, and primarily include hollow structures such as the bladder, as well as vascular structures such as urine tubes.<ref>{{cite journal|last1=Berthiaume|first1=Francois|last2=Maguire|first2=Timothy|last3=Yarmush|first3=Martin|title=Tissue Engineering and Regenerative Medicine: History, Progress, and Challenges|journal=Annual Review of Chemical and Biomolecular Engineering|date=2011|volume=2|pages=403–430|doi=10.1146/annurev-chembioeng-061010-114257|pmid=22432625|url=http://www.annualreviews.org/doi/pdf/10.1146/annurev-chembioeng-061010-114257|accessdate=3 May 2015}}</ref><ref name=A>{{cite web|last1=Cooper-White|first1=Macrina|title=How 3D Printing Could End The Deadly Shortage Of Donor Organs|url=http://www.huffingtonpost.com/2015/03/01/3d-printed-organs-regenerative-medicine_n_6698606.html|website=Huffington Post|accessdate=27 March 2015}}</ref>
A '''printable organ''' is an [[artificial organ|artificially constructed]] device designed for organ replacement, produced using [[3D printing]] techniques. The primary purpose of printable organs is in [[organ transplantation|transplantation]]. Research is currently being conducted on artificial [[heart]], [[kidney]], and [[liver]] structures, as well as other major organs. For more complicated organs, such as the heart, smaller constructs such as [[heart valve]]s have also been the subject of research. Some printed organs have already reached clinical implementation, and primarily include hollow structures such as the bladder, as well as vascular structures such as urine tubes.<ref>{{cite journal |doi=10.1146/annurev-chembioeng-061010-114257 }}</ref><ref name=A>{{cite web|last1=Cooper-White|first1=Macrina|title=How 3D Printing Could End The Deadly Shortage Of Donor Organs|url=http://www.huffingtonpost.com/2015/03/01/3d-printed-organs-regenerative-medicine_n_6698606.html|website=Huffington Post|accessdate=27 March 2015}}</ref>


3D printing allows for the layer-by-layer construction of a particular organ structure to form a cell [[scaffold]]. This can be followed by the process of cell seeding, in which cells of interest are pipetted directly onto the scaffold structure. Additionally, the process of integrating cells into the printable material itself, instead of performing seeding afterwards, has been explored.<ref>{{cite journal|last1=Murphy|first1=Sean|last2=Atala|first2=Anthony|title=3D bioprinting of tissues and organs|journal=Nature Biotechnology|date=August 5, 2014|volume=32|issue=8|pages=773–785|doi=10.1038/nbt.2958|pmid=25093879|url=http://www.nature.com/nbt/journal/v32/n8/full/nbt.2958.html|accessdate=27 March 2015}}</ref>
3D printing allows for the layer-by-layer construction of a particular organ structure to form a cell [[scaffold]]. This can be followed by the process of cell seeding, in which cells of interest are pipetted directly onto the scaffold structure. Additionally, the process of integrating cells into the printable material itself, instead of performing seeding afterwards, has been explored.<ref>{{cite journal |doi=10.1038/nbt.2958 }}</ref>


Modified [[inkjet printer]]s have been used to produce three-dimensional [[biological tissue]]. Printer cartridges are filled with a suspension of living cells and a smart gel, the latter used for providing structure. Alternating patterns of the smart gel and living cells are printed using a standard print nozzle, with cells eventually fusing together to form tissue. When completed, the gel is cooled and washed away, leaving behind only live cells.{{Citation needed|date=June 2015}}
Modified [[inkjet printer]]s have been used to produce three-dimensional [[biological tissue]]. Printer cartridges are filled with a suspension of living cells and a smart gel, the latter used for providing structure. Alternating patterns of the smart gel and living cells are printed using a standard print nozzle, with cells eventually fusing together to form tissue. When completed, the gel is cooled and washed away, leaving behind only live cells.{{Citation needed|date=June 2015}}
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==3D printing techniques==
==3D printing techniques==
3D printing for the manufacturing of artificial organs has been a major topic of study in [[biological engineering]]. As the [[rapid prototyping|rapid manufacturing]] techniques entailed by 3D printing become increasingly efficient, their applicability in artificial organ synthesis has grown more evident. Some of the primary benefits of 3D printing lie in its capability of mass-producing scaffold structures, as well as the high degree of anatomical precision in scaffold products. This allows for the creation of constructs that more effectively resemble the [[microstructure]] of a natural organ or tissue structure.<ref>{{cite journal|last1=Hockaday|first1=LA|last2=Kang|first2=KH|last3=Colangelo|first3=NW|title=Rapid 3D printing of anatomically accurate and mechanically heterogeneous aortic valve hydrogel scaffolds|journal=Biofabrication|date=2012|volume=4|issue=3|doi=10.1088/1758-5082/4/3/035005|pmid=22914604|pages=035005}}</ref>
3D printing for the manufacturing of artificial organs has been a major topic of study in [[biological engineering]]. As the [[rapid prototyping|rapid manufacturing]] techniques entailed by 3D printing become increasingly efficient, their applicability in artificial organ synthesis has grown more evident. Some of the primary benefits of 3D printing lie in its capability of mass-producing scaffold structures, as well as the high degree of anatomical precision in scaffold products. This allows for the creation of constructs that more effectively resemble the [[microstructure]] of a natural organ or tissue structure.<ref>{{cite journal |doi=10.1088/1758-5082/4/3/035005 }}</ref>


Organ printing using 3D printing can be conducted using a variety of techniques, each of which confers specific advantages that can be suited to particular types of organ production. Two of the most prominent types of organ printing are drop-based bioprinting and extrusion bioprinting. Numerous other ones do exist, though are not as commonly used, or are still in development.<ref name=B>{{cite journal|last1=Bajaj|first1=Piyush|last2=Schweller|first2=Ryan|last3=Khademhosseini|first3=Ali|title=3D Biofabrication Strategies for Tissue Engineering and Regenerative Medicine|journal=Annual Review of Biomedical Engineering|date=2014|volume=16|pages=247–276|doi=10.1146/annurev-bioeng-071813-105155|pmid=24905875|url=http://www.annualreviews.org/doi/full/10.1146/annurev-bioeng-071813-105155|accessdate=27 March 2015}}</ref>
Organ printing using 3D printing can be conducted using a variety of techniques, each of which confers specific advantages that can be suited to particular types of organ production. Two of the most prominent types of organ printing are drop-based bioprinting and extrusion bioprinting. Numerous other ones do exist, though are not as commonly used, or are still in development.<ref name=B>{{cite journal |doi=10.1146/annurev-bioeng-071813-105155 }}</ref>


===Drop-based bioprinting (Inkjet)===
===Drop-based bioprinting (Inkjet)===
Drop-based bioprinting creates cellular constructs using individual droplets of a designated material, which has oftentimes been combined with a cell line. Upon contact with the substrate surface, each droplet begins to polymerize, forming a larger structure as individual droplets begin to coalesce. [[Polymerization]] is instigated by the presence of calcium ions on the substrate, which diffuse into the liquified bio-ink and allow for the formation of a solid gel. Drop-based bioprinting is commonly used due to its efficient speed, though this aspect makes it less suitable for more complicated organ structures.<ref name=C>{{cite journal|last1=Auger|first1=Francois|last2=Gibot|first2=Laure|last3=Lacroix|first3=Dan|title=The Pivotal Role of Vascularization in Tissue Engineering|journal=Annual Review of Biomedical Engineering|date=2013|volume=15|doi=10.1146/annurev-bioeng-071812-152428|pmid=23642245|url=http://www.annualreviews.org/doi/full/10.1146/annurev-bioeng-071812-152428|accessdate=1 April 2015|pages=177–200}}</ref>
Drop-based bioprinting creates cellular constructs using individual droplets of a designated material, which has oftentimes been combined with a cell line. Upon contact with the substrate surface, each droplet begins to polymerize, forming a larger structure as individual droplets begin to coalesce. [[Polymerization]] is instigated by the presence of calcium ions on the substrate, which diffuse into the liquified bio-ink and allow for the formation of a solid gel. Drop-based bioprinting is commonly used due to its efficient speed, though this aspect makes it less suitable for more complicated organ structures.<ref name=C>{{cite journal |doi=10.1146/annurev-bioeng-071812-152428 }}</ref>


===Extrusion bioprinting===
===Extrusion bioprinting===
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==Printing materials==
==Printing materials==
Materials for 3D printing usually consist of [[alginic acid|alginate]] or [[fibrin]] polymers that have been integrated with cellular adhesion molecules, which support the physical attachment of cells. Such polymers are specifically designed to maintain structural stability and be receptive to cellular integration. The term "bioink" has been used as a broad classification of materials that are compatible with 3D bioprinting.<ref>{{cite journal|last1=Kesti|first1=Matti|last2=Muller|first2=Michael|last3=Becher|first3=Jana|title=A versatile bioink for three-dimensional printing of cellular scaffolds based on thermally and photo-triggered tandem gelation|journal=Acta Biomaterialia|date=September 23, 2014|volume=11|pages=162–172|doi=10.1016/j.actbio.2014.09.033|pmid=25260606}}</ref>
Materials for 3D printing usually consist of [[alginic acid|alginate]] or [[fibrin]] polymers that have been integrated with cellular adhesion molecules, which support the physical attachment of cells. Such polymers are specifically designed to maintain structural stability and be receptive to cellular integration. The term "bioink" has been used as a broad classification of materials that are compatible with 3D bioprinting.<ref>{{cite journal |doi=10.1016/j.actbio.2014.09.033 }}</ref>


Printing materials must fit a broad spectrum of criteria, one of the foremost being [[biocompatibility]]. The resulting scaffolds formed by 3D printed materials should be physically and chemically appropriate for [[cell growth|cell proliferation]]. [[biodegradation|Biodegradability]] is another important factor, and insures that the artificially formed structure can be broken down upon successful transplantation, to be replaced by a completely natural cellular structure. Due to the nature of 3D printing, materials used must be customizable and adaptable, being suited to wide array of cell types and structural conformations.<ref>{{cite journal|last1=Augst|first1=Alexander|last2=Kong|first2=Hyun Joon|last3=Mooney|first3=David|title=Alginate Hydrogels as Biomaterials|journal=Macromolecular Bioscience|date=March 22, 2006|volume=6|issue=8|pages=623–633|doi=10.1002/mabi.200600069|pmid=16881042}}</ref>
Printing materials must fit a broad spectrum of criteria, one of the foremost being [[biocompatibility]]. The resulting scaffolds formed by 3D printed materials should be physically and chemically appropriate for [[cell growth|cell proliferation]]. [[biodegradation|Biodegradability]] is another important factor, and insures that the artificially formed structure can be broken down upon successful transplantation, to be replaced by a completely natural cellular structure. Due to the nature of 3D printing, materials used must be customizable and adaptable, being suited to wide array of cell types and structural conformations.<ref>{{cite journal|last1=Augst|first1=Alexander|last2=Kong|first2=Hyun Joon|last3=Mooney|first3=David|title=Alginate Hydrogels as Biomaterials|journal=Macromolecular Bioscience|date=March 22, 2006|volume=6|issue=8|pages=623–633|doi=10.1002/mabi.200600069|pmid=16881042}}</ref>
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==Challenges==
==Challenges==
While breakthroughs have been made with regards to producing printable organs, its clinical implementation, namely in regards to complex organs, requires further research. Cell proliferation provided by bioprinting is conducted in an artificial environment, which is devoid of natural [[cell signaling|biological signaling]] and processes; the lack of these qualities inhibits the development of appropriate cellular [[morphology (biology)|morphology]] and [[cell differentiation|differentiation]]. When present, these conditions allow the printed organ to more accurately mimic ''[[in vivo]]'' conditions and adopt the corresponding structure and function, as opposed to growing as a shaped scaffold of cells.<ref>{{cite journal|last1=Athanasiou|first1=Kyriacos|last2=Eswaramoorthy|first2=Rajalakshmanan|last3=Hadidi|first3=Pasha|last4=Hu|first4=Jerry|title=Self-Organization and the Self-Assembling Process in Tissue Engineering|journal=Annual Review of Biomedical Engineering|date=2013|volume=15|doi=10.1146/annurev-bioeng-071812-152423|pmid= 23701238|url=http://www.annualreviews.org/doi/full/10.1146/annurev-bioeng-071812-152423|accessdate=1 April 2015|pages=115–36}}</ref>
While breakthroughs have been made with regards to producing printable organs, its clinical implementation, namely in regards to complex organs, requires further research. Cell proliferation provided by bioprinting is conducted in an artificial environment, which is devoid of natural [[cell signaling|biological signaling]] and processes; the lack of these qualities inhibits the development of appropriate cellular [[morphology (biology)|morphology]] and [[cell differentiation|differentiation]]. When present, these conditions allow the printed organ to more accurately mimic ''[[in vivo]]'' conditions and adopt the corresponding structure and function, as opposed to growing as a shaped scaffold of cells.<ref>{{cite journal |doi=10.1146/annurev-bioeng-071812-152423 }}</ref>


Another challenge is the need to [[angiogenesis|vascularize]] artificial structures for cellular sustainability. Vascular structures, such as [[blood vessel]]s, along with artificial vascular constructs, allow for the diffusion of key [[nutrient]]s and [[oxygen]]. However, they have not been fully integrated into the technique of bioprinting.<ref name=C/>
Another challenge is the need to [[angiogenesis|vascularize]] artificial structures for cellular sustainability. Vascular structures, such as [[blood vessel]]s, along with artificial vascular constructs, allow for the diffusion of key [[nutrient]]s and [[oxygen]]. However, they have not been fully integrated into the technique of bioprinting.<ref name=C/>
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Since 3D printing is a relatively new technology, there is a lot of room for growth. The future trends for printing are growing with each passing day. The following concepts are the trends for the future of 3D organ printing.
Since 3D printing is a relatively new technology, there is a lot of room for growth. The future trends for printing are growing with each passing day. The following concepts are the trends for the future of 3D organ printing.


3D printing with computer aided techniques have allowed for advancements at the cellular level. <ref>Park, J.H., Jang, J., Lee, JS. et al. Tissue Eng Regen Med (2016) 13: 612. doi:10.1007/s13770-016-8111-8.</ref> Currently the idea of fusing living cells with the biomaterials used to create the 3D tissues.<ref>Park, J.H., Jang, J., Lee, JS. et al. Tissue Eng Regen Med (2016) 13: 612. doi:10.1007/s13770-016-8111-8.</ref> This could open the door for many more opportunities for 3D printing. The concept of 3D vascular conduits without scaffolding is being developed currently with hopes of being able to be used in congenital heart surgery. <ref>Munoz-Abraham, A.S., Rodriguez-Davalos, M.I., Bertacco, A. et al. Curr Transpl Rep (2016) 3: 93. doi:10.1007/s40472-016-0089-6.</ref>In addition, branched vascular structures are also being researched. Because of the complexity of branched vascular “trees”, the idea is hard to make into a reality.<ref>Munoz-Abraham, A.S., Rodriguez-Davalos, M.I., Bertacco, A. et al. Curr Transpl Rep (2016) 3: 93. doi:10.1007/s40472-016-0089-6.</ref> The current testing of branched vascular structures is showing successful results in model surgeries, however, further developments need to be made. Another structure being created is the 3D printing of bile ducts. <ref>Munoz-Abraham, A.S., Rodriguez-Davalos, M.I., Bertacco, A. et al. Curr Transpl Rep (2016) 3: 93. doi:10.1007/s40472-016-0089-6.</ref> A huge development is the possibility of the printing of 3D livers. The liver tissue itself is the most difficult to create, and there have been no successful prints to date. Current developments have been able to create the 3D structure of the cells within the liver, making the possibility of a 3D printed liver in the future promising. <ref>Munoz-Abraham, A.S., Rodriguez-Davalos, M.I., Bertacco, A. et al. Curr Transpl Rep (2016) 3: 93. doi:10.1007/s40472-016-0089-6.</ref> In addition to liver printing, developments indicate the 3D printing of the kidney is also possible. Laboratories have been creating blueprints to create 3D renal tissue, a key component to the possible construction of a 3D printed kidney. <ref>Munoz-Abraham, A.S., Rodriguez-Davalos, M.I., Bertacco, A. et al. Curr Transpl Rep (2016) 3: 93. doi:10.1007/s40472-016-0089-6.</ref> Looking ahead, experiments need to be made revolving human interactions with the printing materials before these organs can be placed in a patient.<ref>Radenkovic, Dina. Solouk, Atefeh. Seifalian,Alexander. Personalized development of human organs using 3D printing technology, Medical Hypotheses, Volume 87, February 2016, Pages 30-33, ISSN 0306-9877, http://dx.doi.org/10.1016/j.mehy.2015.12.017. (http://www.sciencedirect.com/science/article/pii/S0306987715004715)</ref> Also, future trends show the possibility of 3D printing the most complex organs in the human body. <ref>Radenkovic, Dina. Solouk, Atefeh. Seifalian,Alexander. Personalized development of human organs using 3D printing technology, Medical Hypotheses, Volume 87, February 2016, Pages 30-33, ISSN 0306-9877, http://dx.doi.org/10.1016/j.mehy.2015.12.017. (http://www.sciencedirect.com/science/article/pii/S0306987715004715)</ref>
3D printing with computer aided techniques have allowed for advancements at the cellular level.<ref>{{cite journal |doi=10.1007/s13770-016-8111-8 }}</ref> Currently the idea of fusing living cells with the biomaterials used to create the 3D tissues.<ref>{{cite journal |doi=10.1007/s13770-016-8111-8 }}</ref> This could open the door for many more opportunities for 3D printing. The concept of 3D vascular conduits without scaffolding is being developed currently with hopes of being able to be used in congenital heart surgery.<ref>{{cite journal |doi=10.1007/s40472-016-0089-6 }}</ref>In addition, branched vascular structures are also being researched. Because of the complexity of branched vascular “trees”, the idea is hard to make into a reality.<ref>{{cite journal |doi=10.1007/s40472-016-0089-6 }}</ref> The current testing of branched vascular structures is showing successful results in model surgeries, however, further developments need to be made. Another structure being created is the 3D printing of bile ducts.<ref>{{cite journal |doi=10.1007/s40472-016-0089-6 }}</ref> A huge development is the possibility of the printing of 3D livers. The liver tissue itself is the most difficult to create, and there have been no successful prints to date. Current developments have been able to create the 3D structure of the cells within the liver, making the possibility of a 3D printed liver in the future promising.<ref>{{cite journal |doi=10.1007/s40472-016-0089-6 }}</ref> In addition to liver printing, developments indicate the 3D printing of the kidney is also possible. Laboratories have been creating blueprints to create 3D renal tissue, a key component to the possible construction of a 3D printed kidney.<ref>{{cite journal |doi=10.1007/s40472-016-0089-6 }}</ref> Looking ahead, experiments need to be made revolving human interactions with the printing materials before these organs can be placed in a patient.<ref>{{cite journal |doi=10.1016/j.mehy.2015.12.017 }}</ref> Also, future trends show the possibility of 3D printing the most complex organs in the human body.<ref>{{cite journal |doi=10.1016/j.mehy.2015.12.017 }}</ref>


The future trends of 3D organ printing show opportunities for growth in almost every aspect. Although there are issues that need to be ironed out, the current developments hold a solid foundation for future endeavors.
The future trends of 3D organ printing show opportunities for growth in almost every aspect. Although there are issues that need to be ironed out, the current developments hold a solid foundation for future endeavors.



==See also==
==See also==
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*[[Rapid prototyping]]
*[[Rapid prototyping]]
*[[Organ transplantation]]
*[[Organ transplantation]]

==References==
{{Reflist}}


==External links==
==External links==
* http://feed.proteinos.com/item/3820
* http://feed.proteinos.com/item/3820
* http://www.newscientist.com/article.ns?id=dn3292
* http://www.newscientist.com/article.ns?id=dn3292
*{{cite journal |doi=10.1002/ar.a.10059 }}
* {{Cite journal|vauthors=Boland T, Mironov V, Gutowska A, Roth EA, Markwald RR |title=Cell and organ printing 2: Fusion of cell aggregates in three-dimensional gels |journal=The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology |volume=272A |issue=2 |pages=497–502 |year=2003 |doi=10.1002/ar.a.10059 |url=http://www3.interscience.wiley.com/cgi-bin/abstract/104525437/ABSTRACT |pmid=12740943}}
*{{cite journal |doi=10.1073/pnas.0400164101 }}
* {{Cite journal|vauthors=Jakab K, Neagu A, Mironov V, Markwald RR, Forgacs G |title=Engineering biological structures of prescribed shape using self-assembling multicellular systems |journal=Proc Natl Acad Sci USA |volume=101 |issue=9 |pages=2864–9 |date=March 2004 |pmid=14981244 |pmc=365711 |doi=10.1073/pnas.0400164101 }}
* [http://www2.umist.ac.uk/material/depment/department/posters04/SaundersR.pdf Saunders] (PDF)
* [http://www2.umist.ac.uk/material/depment/department/posters04/SaundersR.pdf Saunders] (PDF)
* [http://iospress.metapress.com/index/M1R7V0JFNP4148V6.pdf Organ printing: Fiction or science?]
* [http://iospress.metapress.com/index/M1R7V0JFNP4148V6.pdf Organ printing: Fiction or science?]
* [http://scinotions.com/2013/08/regenovo-the-biomaterial-3d-printer-used-to-create-living-tissue Regenovo: the biomaterial 3D printer used to create living tissue]
* [http://scinotions.com/2013/08/regenovo-the-biomaterial-3d-printer-used-to-create-living-tissue Regenovo: the biomaterial 3D printer used to create living tissue]
*{{cite journal |doi=10.1002/ar.b.10025 }}
* {{Cite journal|vauthors=Laitman J, Markwald R |title=What's hot in anatomy: Of talking heads and drawing organs |journal=The Anatomical Record Part B: The New Anatomist |volume=273B |issue=1 |pages=120–1 |year=2003 |doi=10.1002/ar.b.10025 |url=http://www3.interscience.wiley.com/journal/104540959/abstract}}
*{{cite journal |doi=10.1038/nmat1092 }}
* {{Cite journal|vauthors=Luo Y, Shoichet MS |title=A photolabile hydrogel for guided three-dimensional cell growth and migration |journal=Nature Materials |volume=3 |issue= 4|pages=249–53 |year=2004 |doi=10.1038/nmat1092 |url=http://www.nature.com/nmat/journal/v3/n4/abs/nmat1092.html |pmid=15034559}}
* [http://www.pharmacy.utah.edu/medchem/prestwich/Hyaluronan.html pictures]
* [http://www.pharmacy.utah.edu/medchem/prestwich/Hyaluronan.html pictures]
*Munoz-Abraham, A.S., Rodriguez-Davalos, M.I., Bertacco, A. et al. Curr Transpl Rep (2016) 3: 93. doi:10.1007/s40472-016-0089-6.
*{{cite journal |doi=10.1007/s40472-016-0089-6 }}
*{{cite journal |doi=10.1016/j.mehy.2015.12.017 }}
*Radenkovic, Dina. Solouk, Atefeh. Seifalian,Alexander. Personalized development of human organs using 3D printing technology, Medical Hypotheses, Volume 87, February 2016, Pages 30-33, ISSN 0306-9877, http://dx.doi.org/10.1016/j.mehy.2015.12.017. (http://www.sciencedirect.com/science/article/pii/S0306987715004715)
*Park, J.H., Jang, J., Lee, JS. et al. Tissue Eng Regen Med (2016) 13: 612. doi:10.1007/s13770-016-8111-8.
*{{cite journal |doi=10.1007/s13770-016-8111-8 }}


Researchers:
Researchers:
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* Anna Gutowska (developed the thermo sensitive smartgel)
* Anna Gutowska (developed the thermo sensitive smartgel)


==References==
{{Reflist}}


[[Category:Tissue engineering]]
[[Category:Tissue engineering]]

Revision as of 21:49, 1 April 2017

Three-dimensional bioprinter developed by the Russian company, 3D Bioprinting Solutions.

A printable organ is an artificially constructed device designed for organ replacement, produced using 3D printing techniques. The primary purpose of printable organs is in transplantation. Research is currently being conducted on artificial heart, kidney, and liver structures, as well as other major organs. For more complicated organs, such as the heart, smaller constructs such as heart valves have also been the subject of research. Some printed organs have already reached clinical implementation, and primarily include hollow structures such as the bladder, as well as vascular structures such as urine tubes.[1][2]

3D printing allows for the layer-by-layer construction of a particular organ structure to form a cell scaffold. This can be followed by the process of cell seeding, in which cells of interest are pipetted directly onto the scaffold structure. Additionally, the process of integrating cells into the printable material itself, instead of performing seeding afterwards, has been explored.[3]

Modified inkjet printers have been used to produce three-dimensional biological tissue. Printer cartridges are filled with a suspension of living cells and a smart gel, the latter used for providing structure. Alternating patterns of the smart gel and living cells are printed using a standard print nozzle, with cells eventually fusing together to form tissue. When completed, the gel is cooled and washed away, leaving behind only live cells.[citation needed]

History

3D printing for producing a cellular construct was first introduced in 2003, when Thomas Boland of Clemson University patented the use of inkjet printing for cells. This process utilized a modified spotting system for the deposition of cells into organized 3D matrices placed on a substrate.[4][5]

Since Boland's initial findings, the 3D printing of biological structures, also known as bioprinting, has been further developed to encompass the production of tissue and organ structures, as opposed to cell matrices. Additionally, more techniques for printing, such as extrusion bioprinting, have been researched and subsequently introduced as a means of production.[6]

Organ printing has been approached as a potential solution for the global shortage of donor organs. Organs that have been successfully printed and implemented in a clinical setting are either flat, such as skin, vascular, such as blood vessels, or hollow, such as the bladder. When artificial organs are prepared for transplantation, they are often produced with the recipient's own cells.

More complex organs, namely those that consist of solid cellular structures, are undergoing research; these organs include the heart, pancreas, and kidneys. Estimates for when such organs can be introduced as a viable medical treatment vary.[2]

In 2013, the company Organovo produced a human liver using 3D bioprinting, though it is not suitable for transplantation, and has primarily been used as a medium for drug testing.[7]

3D printing techniques

3D printing for the manufacturing of artificial organs has been a major topic of study in biological engineering. As the rapid manufacturing techniques entailed by 3D printing become increasingly efficient, their applicability in artificial organ synthesis has grown more evident. Some of the primary benefits of 3D printing lie in its capability of mass-producing scaffold structures, as well as the high degree of anatomical precision in scaffold products. This allows for the creation of constructs that more effectively resemble the microstructure of a natural organ or tissue structure.[8]

Organ printing using 3D printing can be conducted using a variety of techniques, each of which confers specific advantages that can be suited to particular types of organ production. Two of the most prominent types of organ printing are drop-based bioprinting and extrusion bioprinting. Numerous other ones do exist, though are not as commonly used, or are still in development.[6]

Drop-based bioprinting (Inkjet)

Drop-based bioprinting creates cellular constructs using individual droplets of a designated material, which has oftentimes been combined with a cell line. Upon contact with the substrate surface, each droplet begins to polymerize, forming a larger structure as individual droplets begin to coalesce. Polymerization is instigated by the presence of calcium ions on the substrate, which diffuse into the liquified bio-ink and allow for the formation of a solid gel. Drop-based bioprinting is commonly used due to its efficient speed, though this aspect makes it less suitable for more complicated organ structures.[5]

Extrusion bioprinting

Extrusion bioprinting involves the constant deposition of a particular printing material and cell line from an extruder, a type of mobile print head. This tends to be a more controlled and gentler process for material or cell deposition, and allows for greater cell densities to be used in the construction of 3D tissue or organ structures. However, such benefits are set back by the slower printing speeds entailed by this technique. Extrusion bioprinting is often coupled with UV light, which photopolymerizes the printed material to form a more stable, integrated construct.[6]

Printing materials

Materials for 3D printing usually consist of alginate or fibrin polymers that have been integrated with cellular adhesion molecules, which support the physical attachment of cells. Such polymers are specifically designed to maintain structural stability and be receptive to cellular integration. The term "bioink" has been used as a broad classification of materials that are compatible with 3D bioprinting.[9]

Printing materials must fit a broad spectrum of criteria, one of the foremost being biocompatibility. The resulting scaffolds formed by 3D printed materials should be physically and chemically appropriate for cell proliferation. Biodegradability is another important factor, and insures that the artificially formed structure can be broken down upon successful transplantation, to be replaced by a completely natural cellular structure. Due to the nature of 3D printing, materials used must be customizable and adaptable, being suited to wide array of cell types and structural conformations.[10]

Hydrogel alginates have emerged as one of the most commonly used materials in organ printing research, as they are highly customizable, and can be fine-tuned to simulate certain mechanical and biological properties characteristic of natural tissue. The ability of hydrogels to be tailored to specific needs allows them to be used as an adaptable scaffold material, that are suited for a variety of tissue or organ structures and physiological conditions.[6]

Challenges

While breakthroughs have been made with regards to producing printable organs, its clinical implementation, namely in regards to complex organs, requires further research. Cell proliferation provided by bioprinting is conducted in an artificial environment, which is devoid of natural biological signaling and processes; the lack of these qualities inhibits the development of appropriate cellular morphology and differentiation. When present, these conditions allow the printed organ to more accurately mimic in vivo conditions and adopt the corresponding structure and function, as opposed to growing as a shaped scaffold of cells.[11]

Another challenge is the need to vascularize artificial structures for cellular sustainability. Vascular structures, such as blood vessels, along with artificial vascular constructs, allow for the diffusion of key nutrients and oxygen. However, they have not been fully integrated into the technique of bioprinting.[5]

Ethical debate

As all the technology advances, organ printing brings along all the expectations and ethical debate that divides society. In a statement by Pete Basiliere, research director at Gartner, it “raise(s) a number of questions that remain unanswered. What happens when complex 'enhanced' organs involving non-human cells are made? Who will control the ability to produce them? Who will ensure the quality of the resulting organs?" The rapid emergence of 3D printing will also create major challenges in relation to intellectual property (IP) theft. Gartner predicts that by 2018, 3D printing will result in the loss of at least $100 billion per year in IP globally. In addition, some religious and conservative groups[who?] see organ printing as an immoral manipulation of nature. There are other viewpoints suggesting that organ printing will lead to another issue in social differentiation, with the means to personal organ regeneration limited by financial standing.[12]

Since 3D printing is a relatively new technology, there is a lot of room for growth. The future trends for printing are growing with each passing day. The following concepts are the trends for the future of 3D organ printing.

3D printing with computer aided techniques have allowed for advancements at the cellular level.[13] Currently the idea of fusing living cells with the biomaterials used to create the 3D tissues.[14] This could open the door for many more opportunities for 3D printing. The concept of 3D vascular conduits without scaffolding is being developed currently with hopes of being able to be used in congenital heart surgery.[15]In addition, branched vascular structures are also being researched. Because of the complexity of branched vascular “trees”, the idea is hard to make into a reality.[16] The current testing of branched vascular structures is showing successful results in model surgeries, however, further developments need to be made. Another structure being created is the 3D printing of bile ducts.[17] A huge development is the possibility of the printing of 3D livers. The liver tissue itself is the most difficult to create, and there have been no successful prints to date. Current developments have been able to create the 3D structure of the cells within the liver, making the possibility of a 3D printed liver in the future promising.[18] In addition to liver printing, developments indicate the 3D printing of the kidney is also possible. Laboratories have been creating blueprints to create 3D renal tissue, a key component to the possible construction of a 3D printed kidney.[19] Looking ahead, experiments need to be made revolving human interactions with the printing materials before these organs can be placed in a patient.[20] Also, future trends show the possibility of 3D printing the most complex organs in the human body.[21]

The future trends of 3D organ printing show opportunities for growth in almost every aspect. Although there are issues that need to be ironed out, the current developments hold a solid foundation for future endeavors.

See also

References

  1. ^ . doi:10.1146/annurev-chembioeng-061010-114257. {{cite journal}}: Cite journal requires |journal= (help); Missing or empty |title= (help)
  2. ^ a b Cooper-White, Macrina. "How 3D Printing Could End The Deadly Shortage Of Donor Organs". Huffington Post. Retrieved 27 March 2015.
  3. ^ . doi:10.1038/nbt.2958. {{cite journal}}: Cite journal requires |journal= (help); Missing or empty |title= (help)
  4. ^ Boland, Thomas. "Patent US7051654: Ink-jet printing of viable cells". Google.com. Retrieved 31 March 2015.
  5. ^ a b c . doi:10.1146/annurev-bioeng-071812-152428. {{cite journal}}: Cite journal requires |journal= (help); Missing or empty |title= (help)
  6. ^ a b c d . doi:10.1146/annurev-bioeng-071813-105155. {{cite journal}}: Cite journal requires |journal= (help); Missing or empty |title= (help)
  7. ^ Bort, Julie. "Biotech Firm: We Will 3D Print A Human Liver In 2014". Business Insider. Retrieved 1 April 2015.
  8. ^ . doi:10.1088/1758-5082/4/3/035005. {{cite journal}}: Cite journal requires |journal= (help); Missing or empty |title= (help)
  9. ^ . doi:10.1016/j.actbio.2014.09.033. {{cite journal}}: Cite journal requires |journal= (help); Missing or empty |title= (help)
  10. ^ Augst, Alexander; Kong, Hyun Joon; Mooney, David (March 22, 2006). "Alginate Hydrogels as Biomaterials". Macromolecular Bioscience. 6 (8): 623–633. doi:10.1002/mabi.200600069. PMID 16881042.
  11. ^ . doi:10.1146/annurev-bioeng-071812-152423. {{cite journal}}: Cite journal requires |journal= (help); Missing or empty |title= (help)
  12. ^ Williams R. 3D printing human tissue and organsto 'spark ethics debate'. The Telegraph 29 Jan 2014.
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  20. ^ . doi:10.1016/j.mehy.2015.12.017. {{cite journal}}: Cite journal requires |journal= (help); Missing or empty |title= (help)
  21. ^ . doi:10.1016/j.mehy.2015.12.017. {{cite journal}}: Cite journal requires |journal= (help); Missing or empty |title= (help)

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