Organ printing

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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[edit]

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] Anthony Atala, M.D. (born 1958) is the W.H. Boyce Professor and Director of the Wake Forest Institute for Regenerative Medicine, and Chair of the Department of Urology at Wake Forest School of Medicine in North Carolina.[ 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[edit]

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)[edit]

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[edit]

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[edit]

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[edit]

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]

Essential Components

Approaching the printing process for any specific organ is similar to the way you would approach printing a book. There are five necessary elements involved: a draft, the physical printer itself, a movable type, paper, and ink. All of these components are essential, therefore complications have occurred in regards to the transition from normal printing to organ printing.

Bioink Components

Creating materials that will flourish in the human body is an intricate process. The bioink used in the organ printing process is incredibly more complex than normal printer ink. There are many dependent variables based on the specified organ and patient with regards to unique cells, biomaterials, and biochemical signals. The complexity of these components allow for effectual organ production.[12] In order for the fabricated organ to survive inside the body, biochemical and physical cues must be maintained that promote cell survival. Biochemical cues are associated with growth and adhesion factors, signaling proteins, etc. The physical attributes are components outside the cell and fluid found inside the cell.

Functional Scaffold vs. Scaffold-Free

There are two categories that make up the bioink process, functional scaffold and scaffold-free. Functional scaffold uses biomaterials that may or may not have cells as the actual ink, while scaffold free uses solely cells. The biomaterials used in the functional scaffold process come in a variety of different materials and size. From hydrogels to metal implants, single to multiple nanometers in size - materials created through these stages make up the extracellular (outside the cell) matrix. Throughout these stages elements such as dimensions, internal geometry, anti-degeneration measures, biocompatibility, as well as others must be accounted for.

Material Determinants

When determining the materials used they should be economical and plentiful. This is directly correlated with upholding positive patient care. Materials too expensive or scarce are not going to be accessible for the general public. The four main principles considered when designing them are printability, sufficient physical and chemical properties, biocompatibility, and clinical availability.[13]

Related Wikipedia Articles

  • https://en.wikipedia.org/wiki/3D_cell_culture
  • https://en.wikipedia.org/wiki/Tissue_engineering
  • https://en.wikipedia.org/wiki/Bio-ink
  • https://en.wikipedia.org/wiki/Patient_Protection_and_Affordable_Care_Act

Ethical debate[edit]

As the technology advances, organ printing brings along the expectations and ethical debate that divides society. There are benefits to printing organs for people in need of new organs, but there are also costs to providing this type of treatment.

Pros:

Surgeon Anthony Atala argues that due to the advancements in medicine, people are living longer, which leads to increase in the risk of organ failure. As the need for organs is increasing, the supply of organ donations is staying the same, and people die every day because of organ shortage. Being able to generate an artificial organ from someone’s own cells and other stem cells can prevent people from having to receive many medical treatments like dialysis and surgery. It allows them to live a normal life and keeps them from countless hospital visits.[14]

The journal article, Organ printing: promises and challenges, argues that organ printing may be revolutionary to the future of surgery. Tissue engineers feel that the bioprinter may be able to be used as a surgical tool for tissue building and organ printing can be done on the surgical site.[15]

Izumi International, a 3D printing company, explains that organ printing could also prevent cell rejection. It is challenging to find organ donors with compatible tissues for the patient that needs the organ. Izumi International states that organ printing could possibly put an end to immune system attacks caused by rejection of a donor’s organs because the tissue cells are regenerated from the patient.[16]

Cons:

Pete Basiliere, research director at Gartner, states that organ printing “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?"[17]

The means to personal organ regeneration are limited by financial standing.[17] Professor Susan Dodds also discusses that organ printing is very expensive and treatment would only be available to those who can afford it. [18] The rapid emergence of 3D printing will also create 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.[17]

Dodds also argues that scientists aren’t able to test this treatment like they are with other drugs. They aren’t able to run normal research experiments to make sure the treatment is safe because the organ printed is specific to a patient.[19]

In addition, some religious and conservative groups see organ printing as an immoral manipulation of nature.[17] Dodds questions if we should be able to use 3D printing to improve human health, or are we are enhancing human beings beyond what is normal? This treatment would give people an advantage to those not treated, because they have something artificial in their bodies. This would possibly make them stronger than others and less of a natural human being.[20]

Future Trends[edit]

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.[21] Currently the idea of fusing living cells with the biomaterials used to create the 3D tissues.[21] 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.[22]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.[22] 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.[22] 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.[22] 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.[22] Looking ahead, experiments need to be made revolving human interactions with the printing materials before these organs can be placed in a patient.[23] Also, future trends show the possibility of 3D printing the most complex organs in the human body.[23]

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.

Related Wikipedia Articles:

  • https://en.wikipedia.org/wiki/3D_bioprinting
  • https://en.wikipedia.org/wiki/3D_printing

See also[edit]

References[edit]

  1. ^ Berthiaume, François; Maguire, Timothy J.; Yarmush, Martin L. (2011). "Tissue Engineering and Regenerative Medicine: History, Progress, and Challenges". Annual Review of Chemical and Biomolecular Engineering. 2: 403–30. doi:10.1146/annurev-chembioeng-061010-114257. PMID 22432625. 
  2. ^ a b Cooper-White, Macrina. "How 3D Printing Could End The Deadly Shortage Of Donor Organs". Huffington Post. Retrieved 27 March 2015. 
  3. ^ Murphy, Sean V; Atala, Anthony (2014). "3D bioprinting of tissues and organs". Nature Biotechnology. 32 (8): 773–85. doi:10.1038/nbt.2958. PMID 25093879. 
  4. ^ Boland, Thomas. "Patent US7051654: Ink-jet printing of viable cells". Google.com. Retrieved 31 March 2015. 
  5. ^ a b c Auger, François A.; Gibot, Laure; Lacroix, Dan (2013). "The Pivotal Role of Vascularization in Tissue Engineering". Annual Review of Biomedical Engineering. 15: 177–200. doi:10.1146/annurev-bioeng-071812-152428. PMID 23642245. 
  6. ^ a b c d Bajaj, Piyush; Schweller, Ryan M.; Khademhosseini, Ali; West, Jennifer L.; Bashir, Rashid (2014). "3D Biofabrication Strategies for Tissue Engineering and Regenerative Medicine". Annual Review of Biomedical Engineering. 16: 247–76. doi:10.1146/annurev-bioeng-071813-105155. PMC 4131759Freely accessible. PMID 24905875. 
  7. ^ Bort, Julie. "Biotech Firm: We Will 3D Print A Human Liver In 2014". Business Insider. Retrieved 1 April 2015. 
  8. ^ Hockaday, L A; Kang, K H; Colangelo, N W; Cheung, P Y C; Duan, B; Malone, E; Wu, J; Girardi, L N; Bonassar, L J; Lipson, H; Chu, C C; Butcher, J T (2012). "Rapid 3D printing of anatomically accurate and mechanically heterogeneous aortic valve hydrogel scaffolds". Biofabrication. 4 (3): 035005. Bibcode:2012BioFa...4c5005H. doi:10.1088/1758-5082/4/3/035005. PMC 3676672Freely accessible. PMID 22914604. 
  9. ^ Kesti, Matti; Müller, Michael; Becher, Jana; Schnabelrauch, Matthias; d'Este, Matteo; Eglin, David; Zenobi-Wong, Marcy (2015). "A versatile bioink for three-dimensional printing of cellular scaffolds based on thermally and photo-triggered tandem gelation". Acta Biomaterialia. 11: 162–72. doi:10.1016/j.actbio.2014.09.033. PMID 25260606. 
  10. ^ Augst, Alexander D.; Kong, Hyun Joon; Mooney, David J. (2006). "Alginate Hydrogels as Biomaterials". Macromolecular Bioscience. 6 (8): 623–33. doi:10.1002/mabi.200600069. PMID 16881042. 
  11. ^ Athanasiou, Kyriacos A.; Eswaramoorthy, Rajalakshmanan; Hadidi, Pasha; Hu, Jerry C. (2013). "Self-Organization and the Self-Assembling Process in Tissue Engineering". Annual Review of Biomedical Engineering. 15: 115–36. doi:10.1146/annurev-bioeng-071812-152423. PMC 4420200Freely accessible. PMID 23701238. 
  12. ^ Mironov, Vladimir (2008). "Organ Printing: Promises and Challenges". Regenerative Medicine. 3 (1): 93. doi:10.2217/17460751.3.1.93. 
  13. ^ Cui, Haitao (2017). "3D Bioprinting for Organ Regeneration". Advanced Healthcare Materials. 6 (1). doi:10.1002/adhm.201601118. 
  14. ^ Atala, Anthony. "Printing a Human Kidney". TED Talk | Ted.com. 
  15. ^ Mironov, V; Kasyanov, V; Drake, C; Markwald, RR (2008). "Organ printing: promises and challenges". Regenerative Medicine. 3 (1): 93-103. 
  16. ^ Aslanyan, Larisa. "Advantages of 3D Bioprinting: What the Future Holds." Izumi International Blog. <http://info.izumiinternational.com/advantages-of-bioprinting>.
  17. ^ a b c d Williams, Rhiannon (29 Jan 2014). "3D printing human tissue and organsto 'spark ethics debate'". The Telegraph. 
  18. ^ Dodds, Susan. "3D Printing Raises Ethical Issues in Medicine." ABC - Australian Broadcasting Corporation. 10 Feb. 2015. Web. <http://www.abc.net.au/science/articles/2015/02/11/4161675.htm>.
  19. ^ Dodds, Susan. "3D Printing Raises Ethical Issues in Medicine." ABC - Australian Broadcasting Corporation. 10 Feb. 2015. Web. <http://www.abc.net.au/science/articles/2015/02/11/4161675.htm>.
  20. ^ Dodds, Susan. "3D Printing Raises Ethical Issues in Medicine." ABC - Australian Broadcasting Corporation. 10 Feb. 2015. Web. <http://www.abc.net.au/science/articles/2015/02/11/4161675.htm>.
  21. ^ a b Park, Jeong Hun; Jang, Jinah; Lee, Jung-Seob; Cho, Dong-Woo (2016). "Current advances in three-dimensional tissue/organ printing". Tissue Engineering and Regenerative Medicine. 13 (6): 612–21. doi:10.1007/s13770-016-8111-8. 
  22. ^ a b c d e Munoz-Abraham, Armando Salim; Rodriguez-Davalos, Manuel I.; Bertacco, Alessandra; Wengerter, Brian; Geibel, John P.; Mulligan, David C. (2016). "3D Printing of Organs for Transplantation: Where Are We and Where Are We Heading?". Current Transplantation Reports. 3 (1): 93–9. doi:10.1007/s40472-016-0089-6. INIST:29793152. 
  23. ^ a b Radenkovic, Dina; Solouk, Atefeh; Seifalian, Alexander (2016). "Personalized development of human organs using 3D printing technology". Medical Hypotheses. 87: 30–3. doi:10.1016/j.mehy.2015.12.017. PMID 26826637. 

External links[edit]

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