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3D bioprinting is the process of creating cell patterns in a confined space using 3D printing technologies, where cells can function and survive within the printed construct.[1][2]: 1 Generally, 3D bioprinting utilizes the layer-by-layer method to create tissue-like structures that are later used in medical and tissue engineering fields. [3] Bioprinting covers a broad range of materials . Currently, bioprinting can be used to print tissues and organs to help research drugs and pills.[4] In addition, 3D bioprinting has begun to incorporate the printing of scaffolds. These scaffolds can be used to regenerate joints and ligaments.The first patent related to this technology was filed in the United States in 2003 and granted in 2006.[2]: 1 [5]
Process
[edit]3D bioprinting generally follows three steps, pre-bioprinting, bioprinting, and post-bioprinting. [6][7]
Pre-bioprinting
[edit]Pre-bioprinting is the process of creating a model that the printer will later create and choosing the materials that will be used. One of the first steps is to obtain a biopsy of the organ. The common technologies used for bioprinting are computed tomography (CT) and magnetic resonance imaging (MRI). In order to print with a layer-by-layer approach, tomographic reconstruction is done on the images. The now-2D images are then sent to the printer to be made. Once the image is created, certain cells are isolated and multiplied.[6] These cells are then mixed with a special liquefied material that provides oxygen and other nutrients to keep them alive. In some processes, the cells are encapsulated in cellular spheroids 500μm in diameter. This aggregation of cells does not require a scaffold, and are required for placing in the tubular-like tissue fusion for processes such as extrusion.[1]: 165
Bioprinting
[edit]In the second step, bioprinting, the liquid mixture of cells and nutrients are placed in a printer cartridge and structured using the patients’ medical scans.[8] When a bioprinted pre-tissue is transferred to an incubator, this cell-based pre-tissue matures into a tissue.
3D bioprinting for fabricating biological constructs typically involves dispensing cells onto a biocompatible scaffold using a successive layer-by-layer approach to generate tissue-like three-dimensional structures.*[9] Artificial organs such as livers and kidneys made by 3D bioprinting have been shown to lack crucial elements that affect the body such as working blood vessels, tubules for collecting urine, and the growth of billions of cells required for these organs. Without these components the body has no way to get the essential nutrients and oxygen deep within their interiors.[9] Given that every tissue in the body is naturally compartmentalized of different cell types, many technologies for printing these cells vary in their ability to ensure stability and viability of the cells during the manufacturing process. Some of the methods that are used for 3D bioprinting of cells are photolithography, magnetic bioprinting, stereolithography, and direct cell extrusion.[1]: 196
Post-bioprinting
[edit]The post-bioprinting process is necessary to create a stable structure from the biological material. If this process is not well-maintained, the mechanical integrity and function of the 3D printed object is at risk.[6] In order to maintain the object, mechanical and chemical stimulations are needed. These stimulations send signals to the cells to control the remodeling and growth of the tissues. In addition, in recent development, bioreactor technologies have allowed the rapid maturation of tissues, multi-scale vascularization for survivability of tissues, and the ability to survive transplants.[7] Bioreactors work in either providing convective nutrient transport, creating microgravity environments, changing the pressure causing solution to flow through the cells, or add compression for dynamic or static loading. Each type of bioreactor is ideal for different types of tissue, for example compression bioreactors are ideal for cartilage tissue.[1]: 198
Types of Printers
[edit]Similar to ordinary ink printers, bioprinters have three major components to them. These components are the hardware it uses, the type of bioinnk , and the material it is printed on, or biomaterials.[6] In bioprinting, there are three major types of printers that have been used. These are inkjet, laser-assisted, and extrusion printers.
Inkjet printers are mainly used in bioprinting for fast and large-scale products. One type of inkjet printer, called drop-on-demand inkjet printer, prints materials at exact amounts, minimizing cost and waste. Printers that utilize lasers provides high-resolution printing. However, these printers are often expensive. Extrusion printers print cells layer-by-layer, just like 3D printing to create 3D constructs. In addition to just cells, extrusion printers also use hydrogels infused with cells. [6]
Applications
[edit]San Diego-based Organovo, an "early-stage regenerative medicine company", was the first company to commercialize 3D bioprinting technology.[2]: 1 The company utilizes its NovoGen MMX Bioprinter for 3D bioprinting. The printer is optimized to be able to print skin tissue, heart tissue, and blood vessels among other basic tissues that could be suitable for surgical therapy and transplantation. A research team at Swansea University in the UK is using bioprinting technology to produce soft tissues and artificial bones for eventual use in reconstructive surgery. Bioprinting technology will eventually be used to create fully functional human organs for transplants and drug research. This will allow for more effective organ transplants and safer more effective drugs.*[10]
Further advancements
[edit]As well as being used for growing organs, this newer biotechnology is also being used to create skin for prosthetic limbs and for skin grafts.[11][12] By taking a few live skin cells and applying bioengineering, limbs can be designed on a computer. The object, such as a prosthetic limb organs, can be customized to fit an amputee’s needs or a patient in need of a transplant. The 3D printer will print out these objects using nanotechnology, layer by layer, in less than an hour.[13]
In early 2015, 3-D printing techniques expanded to include materials such as graphene, a material possessing unique properties such as high levels of strength, rather than only plastics.[14] Researchers have since proved that printing graphene using a micropipette technique to create nanostructures is possible.[15] The nanostructures and graphene structures that are printed can create various objects, including architectures and woven structures. Using a computer, science and healthcare professionals can take X-rays and molds from a patient to recreate a specialized prosthetic that is customized to fit the patient. This allows the prosthetics to be more comfortable and function more naturally. In the future, this technology will change the face on medicine and manufacturing. This technology has great potential for the NBIC (nano-, bio-, info-, and cognitive-based technologies) to strategically make advancements in medicine and in surgical procedures that will greatly save time, costs, and create more convenient opportunities for patients and healthcare professionals.[12][16]
Impact
[edit]3D bioprinting contributes to significant advances in the medical field of tissue engineering by allowing for research to be done on innovative materials called biomaterials. Biomaterials are the materials adapted and used for printing three-dimensional objects. Some of the most notable bioengineered substances are usually stronger than the average bodily materials, including soft tissue and bone. These constituents can act as future substitutes, even improvements, for the original body materials. Alginate, for example, is an anionic polymer with many biomedical implications including feasibility, strong biocompatibility, low toxicity, and stronger structural ability in comparison to some of the body's structural material.[17] Synthetic hydrogels are also commonplace, including PV-based gels. The combination of acid with a UV initiated PV based cross-linker has been evaluated by the Wake Forest Institute of Medicine and determined to be a suitable biomaterial.[18] Engineers are also exploring other options such as printing micro-channels that can maximize the diffusion of nutrients and oxygen from neighboring tissues [8] In addition, The Defense Threat Reduction Agency aims to print mini organs such as hearts, livers, and lungs as the potential to test new drugs more accurately and perhaps eliminate the need for testing in animals.[8]
See also
[edit]References
[edit]- ^ a b c d Chua, C.K.; Yeong, W.Y. (2015). Bioprinting: Principles and Applications. Singapore: World Scientific Publishing Co. p. 296. ISBN 9789814612104. Retrieved 17 February 2016.
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: CS1 maint: multiple names: authors list (link) - ^ a b c Doyle, Ken (15 May 2014). "Bioprinting: From patches to parts". Gen. Eng. Biotechnol. News. 34 (10): 1, 34–5. doi:10.1089/gen.34.10.02.
- ^ "Advancing Tissue Engineering: The State of 3D Bioprinting". 3DPrint.com. Retrieved 2016-03-24.
- ^ "ExplainingTheFuture.com : Bioprinting". www.explainingthefuture.com. Retrieved 2016-03-24.
- ^ US patent 7051654, Boland, Thomas; Wilson, Jr., William Crisp; Xu, Tao, "Ink-jet printing of viable cells", issued 2006-05-30
- ^ a b c d e Shafiee, Ashkan; Atala, Anthony (2016-03-01). "Printing Technologies for Medical Applications". Trends in Molecular Medicine. 22 (3): 254–265. doi:10.1016/j.molmed.2016.01.003.
- ^ a b Ozbolat, Ibrahim T. (2015-07-01). "Bioprinting scale-up tissue and organ constructs for transplantation". Trends in Biotechnology. 33 (7): 395–400. doi:10.1016/j.tibtech.2015.04.005.
- ^ a b c Cooper-White, M. (1 March 2015). "How 3D Printing Could End The Deadly Shortage Of Donor Organs". Huffpost Science. TheHuffingtonPost.com, Inc. Retrieved 17 February 2016.
- ^ a b Harmon, K. (2013). "A sweet solution for replacing organs" (PDF). Scientific American. 308 (4): 54–55. doi:10.1038/scientificamerican0413-54. Retrieved 17 February 2016.
- ^ Thomas, D. (25 March 2014). "Engineering Ourselves – The Future Potential Power of 3D-Bioprinting?". Engineering.com.
- ^ Dorminey, B. (February 26, 2013). "Nanotechnology's Revolutionary Next Phase". Forbes Magazine. Retrieved October 24, 2015.
- ^ a b Berger, M. (September 26, 2014). "Nanotechnology and 3D-printing". Retrieved October 24, 2015.
- ^ "Could 3D Printing Change the World? Technologies, Potential, and Implications of Additive Manufacturing" (PDF). Atlantic Council. October 1, 2011. Retrieved October 24, 2015.
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ignored (help) - ^ Tampi, Tarun (19 March 2015). "Graphene Filament Could Breathe Life into 3D Printing". 3D Printing Industry. Retrieved 17 February 2016.
- ^ Krouse, C. "Nanotechnology Skin for Prosthetic Arms". Nanowerk.com. Retrieved October 24, 2015.
- ^ Krassenstien, B. (27 November 2014). "Breakthrough Research Leads to the 3D Printing of Pure Graphene Nanostructures". Retrieved 24 October 2015.
- ^ Crawford, M. (May 2013). "Creating Valve Tissue Using 3-D Bioprinting". ASME.org. American Society of Mechanical Engineers. Retrieved 17 February 2016.
- ^ Murphy, S.V.; Skardal, A.; Atala, A. (2013). "Evaluation of hydrogels for bio-printing applications". Journal of Biomedical Materials Research Part A. 101A (1): 272–84. doi:10.1002/jbm.a.34326. PMID 22941807.
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: CS1 maint: multiple names: authors list (link)