BioPlotting Is People
Fully 3D printed organs are on their way, with much room for improvement
One of the more innovative, and potentially world-changing areas of 3D printing revolves around the medical industry and producing printable implants and organs. EnvisionTEC’s 3D-Bioplotter was first conceived in 1999 at the Freiburg Material Research Center in Freiburg, Germany. Now on its fourth generation, it’s used in research and development as well as rapid prototyping.
Having the ability to 3D print organs is not an original idea, as it is in various investigation stages across many institutions worldwide, but the 3D-Bioplotter, and similar machines, have been the primary movers in this research. Stepping toward fully 3D-printable organs, EnvisionTEC creates scaffolds, or bio-compatible constructs that help the body regenerate from damage. Tissue engineering requires these 3D scaffolds with well-defined external and internal structures. The 3D-Bioplotter fabricates the scaffolds in a familiar rapid prototyping fashion.
“[These bio-compatible constructs] are slowly absorbed by the body while it creates new bone or tissue to replace them,” according to Carlos Carvalho, part of the Process & Material Development department at EnvisionTEC. “In Luc Besson's film The Fifth Element, the character played by Milla Jovovich is fully 3D printed from a few strands of DNA. It is not possible to get a beating heart out of a 3D printer at this time, but this film also takes place 200 years in the future.”
Not as Simple as It Looks
With traditional additive manufacturing, materials are laid down, layer by layer, to create a completed part or component. A concept that seems simple and intuitive to the process. When it comes to tissue engineering, researchers are able to print large groups of cells in three dimensional shapes and, through special nurturing, make it partially function as the tissue it represents.
“You need to harvest a small amount of cells from a patient, then cultivate and multiply them over a period of weeks or even months, depending on the size of your printed object, to have enough to print organs,” Carvalho explains. “While printing, sterility must be kept at all times and optimal cell conditions must be met – stress to the cells must be minimized.”
Even after the printing is completed the structure has to be incubated in bioreactors, where chemical, biological, and mechanical environments are optimized for cell growth, tissue creation, and functionalization.
“The greatest difficulty when printing a full or partial organ is obtaining the raw material – the enormous amount of cells required,” he adds. For example, a human liver contains around 100 billion cells and weighs about 1.5 kg. “This means that if you take a small 1 g biopsy from a patient, you still need to grow the cells to 1,500 times the obtained amount.”
The 3D-BioPlotter uses an array of 3D technologies. Computer tomography data, or sectioned images, are saved in a DICOM (Digital Imaging and Communications in Medicine) format and transferred to an STL. From there, the appropriate scaffold is modeled or the organ is designed in CAD software. “While STL is the de facto industry standard, it is proving itself to be increasingly lacking, especially in the medical field with highly complex, multi-material, and multi-cellular parts. Other formats have been proposed, the most prominent being AMF (Additive Manufacturing File), developed by ASTM (American Society for Testing and Materials) in 2011,” Carvalho says.
The BioPlotter uses up to five extruders to create a single object. This means any object constructed can be made out of five different materials or five different types of cells placed in very specific positions of the part.
For the printing process, air pressure is applied to a cartridge housing a liquid or a paste, and by moving the cartridge with a needle tip, the 3D object is fabricated. “The plotter’s key feature is the flexibility in the choice of materials and solidification processes,” Carvalho says. “You can use polymer melts up to 250°C, which solidify simply through the change in temperature. You can use ceramic pastes with bone materials, which solidify into pure ceramic objects after sintering. Or you can use nearly any type of hydrogel, like collagen or alginate, each with its own individual solidification process. Because it is capable of printing into a bath, the process can be a chemical reaction, an ionic exchange, or precipitation.”
Trepidation for Printed Organs
Unlike stem cell research, 3D organ printing has experienced little blowback in terms of public perception. “Printing organs is not about giving a sportsman an extra edge or creating the super soldier,” Carvalho explains. “Printing organs is about saving lives. In the best of cases, it will be giving a patient in desperate need for a new organ an additional choice between another human's transplant, an animal transplant, a purely artificial organ, or a printed organ which uses the patient's own cells.” The United Network for Organ Sharing (UNOS) has more than 120,000 people registered and waiting for a transplant.
Advances in organ printing and tissue engineering have been welcomed by the media and the public, but according to Carvalho, “Ultimately, it will always be the patient's own ethics and decision to use a 3D printed scaffold or organ, or not.”
“The most promising research is being done in printing livers. The liver is the only organ in the human body that can regenerate itself, but at the same time, the only option for patients with irreversible liver failure is a transplant from a living donor,” says Carvalho. “Realistically speaking we will probably see printed, functional livers in 20 years time.”
Fully 3D printed organs are on their way, with much room for improvement. EnvisionTEC has experience in the realm of medical design and 3D printing, but the route to full approval in the United States is a rough road. Once the organs are fully printable, the journey to FDA approval begins.
The development of this technology has already picked up the pace in recent months, and now, according to Carvalho, the more research groups and industry partners that get invested in this research and technology, the faster it can help those people in donor waiting lists. If the sudden adoption of 3D printing by the public is any indication of progress, 20 years until functional livers could be a very conservative estimate.