by Earl Prinsloo
“Dude, print me a new liver?” may become a commonplace request in the not too distant future. Three dimensional bioprinting is the rapidly advancing "new biotech kid on the block" born from a method known as additive manufacturing technology or more commonly, 3D printing. The rapid growth in the open source "Maker" movement has spurred the incremental leaps in the potential printing of human tissues.
"Computer, Tea, Earl Grey, Hot"
Any fan of Star Trek - The Next Generation will tell you that the request above was often repeated by Captain Jean-Luc Picard aboard the Starship Enterprise when he needed his favourite beverage after a long hard day battling the Borg. The fictional replicator technology would then synthesize an appropriate container and its contents. This example is used by many a user/advocate of 3D printing as the ultimate in additive manufacturing, i.e multiple material printing (inorganic - the cup and organic - the tea).
Consider a traditional inkjet desktop printer that prints in a traditional two dimensional space, i.e. a X and Y coordinate space. Technically a flat surface. Three dimensional printers add an additional Z space coordinate (or more simply an Up coordinate); effectively adding height.
Additive manufacturing is currently experiencing an explosive boom following the start of the RepRap (replicating rapid prototyper) open source (www.reprap.org) project in 2005. The Fused Filament Fabrication (FFF) system promoted by the RepRap 3D printers simply uses a heated moving printing head to melt plastic to build a layer upon layer recreation of a 3D computer model. Models can be designed in any software package e.g. Blender (www.blender.org) and exported to the format required by the printer.
The open hardware nature of the RepRap project allows anyone to modify and improve upon the design resulting in a myriad of 3D printing systems e.g. Makerbot Replicator 2 or the Ultimaker. This has extended to the South African shores with the establishment of www.openhardware.co.za, a vendor dedicated to open hardware 3D printer kits and other open hardware components.
Typically 3D printers print plastic materials with high melting temperatures (> 180°C). The plastics range from acrylonitrile butadiene styrene (ABS)) to a biodegradable polylactic acid (PLA). The temperatures at which these plastics melt are however too high for printing living materials like mammalian cells or even single proteins. Using the "tinker-friendly" technology, users wanting to print biological materials have turned to alternative methods of delivering materials to the printerhead for deposition and layering; the most notable being air pressurized syringes or traditional inkjet technology (yes, the same as the printer sitting on your desktop). The problem is that cells do not necessarily stick to one another once printed, unless they are held together for a given amount of time. Hence most bioprinting involves the printing of a scaffold. A rigid (but flexible enough), biodegradable material (e.g. a gel) that will allow the cells to grow on (and in) it and form tissues of an organ.
"I'll have my steak...printed"
How about a printed steak? A US based biotech company called Modern Meadow is betting big that the world’s population will one day rely on 3D printed meat to meet (pardon the obvious pun) its food protein requirements. Big investors are onboard to facilitate the final development and commercialisation of Modern Meadow’s technology which aims to print and grow animal muscle tissue in vitro. The major obstacle is time and cost. It was recently estimated that a 3D printed hamburger patty would cost about US$ 300 000. Obviously, too expensive for the mass market, but the potential is there.
Tissue and Organ Engineering
A major problem with printing and growing new tissues and organs is the complexity of an organ. The example given above of Modern Meadow’s animal muscle tissue/meat printing is a simple one. The meat will be printed for consumption. Tissue printing for transplantation requires whole new approaches that factor in the different cell types that make up a specific organ as well as the blood system that will deliver nutrients and remove waste from the tissue. Researchers at the University of Pennsylvania are working on the development of technology to print sugar (yes, edible sugar) networks, that will form the basis of a simple artificial blood system once cells grow around them and consume the sugar (or the sugar network could be dissolved. This is a very basic but elegant approach that they hope will allow for the development of an artificial liver with a workable artificial vasculature.
Science is at a stage currently where we can print scaffolds to coax cells to grow on and in them to form very simple bodily organs (e.g. plastic PLA scaffolds in the shape of an ear). Scientists at the Wake Forest Institute for Regenerative Medicine have pioneered methods of printing scaffolds for bladders & kidneys and are progressing to developing inkjet printing technology to 3D print tissues without a scaffold. On the more “simple” end of the scale, researchers at the University of Edinburgh have created a 3D printer to print living human embryonic stem cells in uniform droplets. It is hoped that this will facilitate the development of further technologies to be used in drug safety testing and eventually to print stem cells for tissue engineering.
The Next Step
Recently the US based biotech startup Organovo announced a partnership with 3D software giant Autodesk to develop 3D software specifically to facilitate the 3D printing of organs in the future. Organovo are pioneers in the field of inkjet bioprinting with the Novogen MMX Bioprinter which prints simple 3D tissue layers which they use for drug toxicity testing to mimic in vivo living systems. The partnership with Autodesk is to allow for the next step, i.e. easy 3D printing of cells into fully developed organs. The software will interface with the printer to tell it what type of cell needs to be printed where in 3D space and what type of structure needs to be printed to make a whole organ.
The hardware is evolving at a rapid rate and scientists are developing new ways of building living tissues with functional blood systems that will one day, hopefully, facilitate a biotechnology revolution that will eliminate long waiting lists for new organs (hearts, livers etc) for organ donation.
* Earl Prinsloo is with the Biomedical Biotechnology Research Unit in the Department of Biochemistry, Microbiology and Biotechnology at Rhodes University