SciRL is a new segment exploring scientific applications in real life. On this week's segment, what is 3D printing and how can we harness this new technology to make progress in the field of medicine?
Resources / Links:
- What is 3D Printing? (3dprinting.com, Wikipedia, Carbon3d.com)
- Joseph DeSimone: What if 3D printing was 100x faster? (Video)
- Japanese 3D printing company creates models of your live fetus (Article, Video)
- Ben Heck Answers Your 3D Printing Questions (Video)
- How a 3D Printer Works (Video)
- Anthony Atala: Printing a human kidney (Video)
- Animation of the FDM process (Video)
- Hideo Kodama, "Automatic method for fabricating a three-dimensional plastic model with photo-hardening polymer," Review of Scientific Instruments, Vol. 52, No. 11, pp 1770-1773, November 1981
- Hideo Kodama, "A Scheme for Three-Dimensional Display by Automatic Fabrication of Three-Dimensional Model," IEICE TRANSACTIONS on Electronics (Japanese Edition), vol.J64-C, No.4, pp.237-241, April 1981
- Murphy, S. V., & Atala, A. (2014). 3D bioprinting of tissues and organs. Nature biotechnology, 32(8), 773-785.
- 3D printed organs come a step closer (Article)
- Custom organs, printed to order (Article, PBS NOVA)
- Print Thyself (Article, New Yorker)
- First 3D-printed pill approved by US authorities (Article, BBC)
- Why it matters that the FDA just approved the first 3D-printed drug (Article, Washington Post)
3D Printing. A phrase that seems more science fiction than reality...although that phrase probably describes a lot of modern science and technological advancements these days. We may have seen some of the incredible things that 3D printers can create, but how are they creating things out of what looks like thin air? And what kind of applications does 3D printing have for science and medicine in our future?
How 3D Printing Works
So 3D printing (also known as additive manufacturing) is essentially the process of taking a digital file and creating a real 3D product by constructing physical 2D slices of that digital file layer by layer.
You basically start out with a virtual design of the object you want to create...let's say you really want to print out a tiny guitar frame. These virtual designs are made in a Computer Aided Design or CAD file using a type of 3D modeling program or if you're copying an existing object, you can use a 3D scanner. There are some neat YouTube videos I'll link in the show notes that show these types of softwares and how to create and prepare a digital file. Once ready for printing, the 3D modeling software needs to "slice" the digital model in many, many horizontal layers. The printer can then read those slices and then create the object by printing layer by layer additively on top of each other until the final 3D object is complete.
There are many different types of 3D printers out there, including FDM, STL, and Powder Deposition Fusion, CLIP, and more.
- FDM or Fused Deposition Modeling
- STL or Stereo Lithography
- Powder Deposition Printing
- CLIP or Continuous Liquid Interface Production Technology
Now FDM printers are among the most common types of 3D printers out there and typically use either one of two types of plastic filament materials. Either ABS (acrylonitrile butadiene sytrene) or PLA (polylactic acid) are typically used as a type of plastic material that is heated in what's called the extrusion nozzle and then deposited in layers, with the melted plastic hardening as it exits the nozzle. While we envision this type of technology to be fairly new, FDM technology was actually invented back in the late '80s by Scott Crump, who patented the technology and created the Stratasys company in 1988. The actual concept and equipment associated with additive manufacturing were developed just a touch earlier in 1981 by Hideo Kodama of Nagoya Municipal Industrial Research Instritute. Kodama invented two different fabrication methods of a 3D plastic model with a polymer that is hardened by UV light, and the UV light exposure area is controlled using certain transmitters and other technologies. A few years later, in 1984, Chuck Hull of 3D Systems Corporation had developed a prototype system based on this idea called stereolithography, where polymer layers are essentially "cured" by UV lasers. But plastic isn't the only substrate that can be used in 3D printers. If it can flow through a print-head and eventually harden, it can be used as 3D printer "ink", meaning anything from plastic to wood pulp to...human cells and proteins.
Applications in Healthcare
3D Printed Organs
Some sources report that over 123,000 people in the United States alone are in need of an organ transplant, yet only about 14,000 people are actually suitable to donate their organs. Engineering pig organs to express human proteins may be an interesting way to solve our organ shortage, but problems soon arise with incompatibilities between species, whether that be in blood clotting proteins that cause blockages or uncontrolled bleeding or in the form of immune attacks on the transplanted organ.
What if there was a way to provide organs to human patients that need them without these high risks of immune problems and rejection from the host body? What if you could use the patient's own biomaterial in this organ? With the idea of 3D printing on the table, we can do just that.
In 2003, Dr. Thomas Boland at Clemson University patented what he called "ink-jet printing of viable cells". Using stereolithography, or STL 3D printing technology, scaffolds of human organs can be printed using a biocompatible material. Scientists can then bathe these organ scaffolds with cells and nutrients and allow the cells to proliferate and remold the scaffold as they continue to grow. These cells and proteins can come from the patient in question, meaning less likelihood of organ transplant rejection. One of the advantages of using STL 3D printing is that structures can be built on a submicron level, meaning that researchers can print biocompatible materials that can interact on a cellular or sub-cellular level. Using this new technology, the complexity of organ structure can be replicated outside of the body.
This is precisely what Anthony Atala is doing at the Wake Institute for Regenerative Medicine. In fact, he performed a TED talk a few years back where a 3D bioprinter in the background of his talk was printing what looked like a kidney as he delivered his speech. Atala's lab is set on trying to successfully 3D print an entire human kidney, ready and available for use in kidney transplants. Prior to this, Dr. Atala had been able to use 3D printing to grow human bladder tissue on biodegradable scaffolds, which were then successfully implanted around the bladders of 7 young patients with poor bladder function, thereby relieving their condition.
But we may be a while away from actually printing out 3D organs at the local hospitals for immediate organ transplants. At the moment, the only real, functional tissue that can be made for a transplant situation is skin. Making an entire functional organ requires much more than just layered cells, it requires integration of vasculature and nerves and proper cell-cell communication. Some claim that 3D printing simply cannot achieve that level of complexity.
That's where Jennifer Lewis comes in. Back in 2011, in collaboration with Scott White and Nancy Sottos, Lewis developed something called Pluronic ink. This ink is a material that appears gelatinous at room temperature but then turns into a liquid when exposed to temperatures just above freezing. A little counterintuitive, I know. But Lewis and White were able to use this Pluronic-ink gel to create plastic objects with detailed networks of this Pluronic material embedded into the final product. When the object is completed, it can be cooled down and the Pluronic ink, now in liquefied form, can be sucked out, leaving behind empty channels. Lewis fondly refers to the Pluronic ink as "fugitive ink" for that very reason. In 2013, Lewis started her own lab at the Wyss Institute for Biologically Inspired Engineering, where she is working on making vasculature possible using her fugitive ink. Her lab can do much the same thing by printing out a vasculature system, say of the lungs or the heart, using Pluronic ink and then sucking up the cooled down, liquefied product. What's left is an intricate, hollow vessel system that can then be injected with endothelial cells, the cells that line the insides of blood vessels. Ideally, what you're left with are working blood vessels with happy endothelial cells that can also branch off the existing vessels to create new ones. Lewis describes this as a more natural environment for blood vessel growth versus a petri dish or an inorganic scaffold. If integrated into an organ print, additional ink dispensers would print out a lattice of collagen and fibroblasts around the fugitive ink network, effectively encasing the printed vasculature with living tissue. Then the entire biomaterial product would be cooled down, the ink sucked out, and the endothelial cells injected into the empty space to create a printed organ with vasculature. Other folks from Carnegie Mellon and Brigham and Women's Hospital are working on a "micro-robot" to arrange cells in a specific structure using magnetic control systems, while yet more groups at Boston U, Rice University, and MIT are trying to create 3D printed vascular channels with sugar-based inks. If we move one step closer towards creating a real organ, it could be the start of something big for the medical industry.
Not only could 3D printed organs be printed out for transplant purposes, but they could also serve their role in drug development studies. A San-Diego based company called Organovo is currently utilizing 3D tissue printing to create what they call "organs on a chip". These are bio systems that simulate to some degree the environment of a specific organ, such as liver tissues, thereby allowing researchers to test drugs and treatments on these cells instead of having to use model organisms in drug treatment trials. Testing directly on human cells without testing on an actual human being can prove very beneficial and cost-effective, and the cells can come from anywhere: an established cell line in the research field, a patient's cells, or stem cells. Physicians and medical students can also use bioprinted materials in the classroom to practice incisions and learn anatomy, while medical supply companies can utilize 3d printed anatomical models to help design better prototypes for medical devices like heart valves and prosthetics. But organs aren't the only things that 3d printers can bring to the field of medicine. We may not be able to print up a kidney for someone today, but if you're in need of an Aspirin or two, we might have you covered.
3D Printed Pills
So maybe not quite an Aspirin, since that's a bit of a legal issue, but as of earlier this month, the US Food and Drug Administration has just approved the production of 3D printed pills. This new drug, called Spritam, is designed for patients suffering from epilepsy and is meant to help control symptomatic seizures. Spritam is developed by Aprecia Pharmaceuticals, a company that is intent on developing other types of medication using this same approach of 3d printing. But what's the real advantage to printing pills? I mean, we already have a way to make them, why bring in fancy equipment to do the job?
3D printing actually allows a more precise packaging of the relevant drug into its pill form. Since the technology relies on its layering effect, this allows the layers of medication to be packaged more tightly in a tablet or pill, thereby allowing for production of more precise dosages. Aprecia has developed this technology and called it ZipDose, a process that makes it easier to consume higher doses of medication in a single tablet. And by higher doses, we mean up to 1,000 mg in an individual tablet. For reference, your average Aspirin dosage is usually around 325 mg per tablet. Low-dose (or "baby-strength") Aspirin is around 81 mg. The physical composition of the Spritam pill itself is also more porous than your average pill, allowing for instant dissolution when in contact with liquid. This means that the pill will literally melt in your mouth when you take a sip of water to wash it down.
What this means for medicine is that doctors and patients can work out a patient-specific dosage, a more customizable approach to medication versus what some call "a one size fits all approach". Each tablet that's printed has the exact dosage of medication that was designed to be printed into it. As of this recording, Aprecia Pharmaceuticals has already been awarded more than 50 patents related to 3d printed pharmaceutical applications. The company intends to bring more effective neurological drugs to the market by harnessing this new technology, and it's very likely that many other pharmaceuticals may follow suit.
Organs and pills aren't the only benefits that 3D printing has brought to the table that is the medical industry. Some places are using bioprinting technology to provide pregnant mothers with a physical, 3D tangible image of what their babies look like inside their bellies. Folks at a health clinic in Ebisu, Tokyo called Hiro-o Ladies is working with a 3D printer called Fasotec to create Tenshi no Katachi - Shape Of An Angel. Ultrasound images taken of the pregnant mother can be digitally sliced into 2D images and sent to a 3D printer. The printer utilizes a dual-resin extruder to make the baby part and solidified amniotic part at the same time, essentially printing out a a resin-cast 3D model of your live fetus floating in clear lucite.
So whether it's bladder tissue grown with your own cells and DNA, or maybe your customized dosage of seizure medication, or perhaps a fun little model of your baby to hold as you wait to give birth...3D printing can offer all these things and probably more as we continue to explore the possibilities available with this new technology. As with any new tech, certain ethical issues arise, the main one around 3d printing being the question of intellectual copyright and safety. Can we print out iPods instead of buying one? What about handguns? Can we print a cheaper version of an expensive product and sell it as our own? But just as with all other technologies, the industry and the market and the consumers have figured out ways to balance these things out, and you can expect to see progress in the 3d printing community when it comes to these types of questions.
Sound effects used in this episode are from www.freesfx.co.uk.
Music used in this episode (in order of appearance): "Fast Talkin" // "Universal" // "Unwritten Return" // "Mining by Moonlight" // "Bass Walker" // "Cold Funk" All music tracks are attributed to Kevin MacLeod and are licensed under Creative Commons: By Attribution 3.0 creativecommons.org/licenses/by/3.0/. All audio clips added to the podcast are used for nonprofit, educational purposes.
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