By Ed Ruth
Recent advances in 3-D printing technology are creating whole new subsectors of the healthcare industry and enabling healthcare organizations to offer healthcare solutions that just a few years ago would have been unimaginable. In healthcare, there is 3-D printing of objects, such as implants and other items that will be discussed below. And then there is 3-D printing of living cells, sometimes called “Bioprinting”.
The affect 3-D printing will have on healthcare is going to be amazing. According to InformationWeek, 3-D printing in the Healthcare Industry is only set to continue growing. The market is expected to expand to more than $4 billion by 2018. Custom prosthetics, braces, casts, etc will be created in very short time at a very low cost. And custom medical implants, such as hip joints, can be produced at a fraction of the time and cost. The customized creation of parts specific to an individual is a key advantage to 3-D printing in Healthcare. For example, a 3-D printed implant in a child would be printed to the exact size needed for their body. As the child matured and their body grew, the part might need to be replaced. The replacement could just as easily be custom printed to meet their changing needs. The customization also enables quicker surgeries and faster healing.
The healthcare industry is seeing a large assortment of uses for 3-D printing. 3-D printing of dental implants creates much faster and less expensive implants that the current process of milling out a block of polymer. Many people with custom-manufactured hearing aids, replacement knees and prosthetics can already thank 3-D printing for changing their healthcare. For example, a researcher at the famed MIT Media Lab has developed a method of using MRI scans to identify stress points on an amputee patient’s remaining limb portion to develop a limb socket that is unique to that patient and drastically improves the comfort of wearing the prosthetic. 3-D printing has also been already used in the creation of reconstructive implants for jawbones and other parts of the skull. 3-D printing even offers the ability to print complete lab devices. But some of the most exciting recent developments in 3-D printing in healthcare are related to Bioprinting, the printing of living cells.
Challenges of Organ Printing: The holy grail of Bioprinting is 3-D printing of whole functional organs. Nearly 120,000 people in the United States are on the waiting list for an organ transplant that may save their lives, according to the American Transplant Foundation. If you’ve ever read anything on organ transplants, you know that a huge problem with transplanting a donor organ is what is known as “organ rejection”. Basically, a transplant recipients’ own immune system recognizes the transplanted organ as foreign and tries to fight it off. A variety of immuno-suppressant drugs are given to the organ recipient to fight off those rejection efforts. but doing so is sometimes not successful and opens the patient up to other issues since they have a much lowered immune system.
The ideal way to reduce or stop this rejection of the organ would be to use the patients own stem cells to grow a replacement organ. This would drastically reduce the danger of rejection, offer a higher rate of healing and improve the patients chances of long-term recovery. There are, however, several significant challenges that must be overcome before this becomes a reality. The two most daunting challenges seem to be the growth of tissue or organs with the complexity and structure to include both vascular and nervous system capabilities.
Hospitals have for many years been able to grow single layers of epithelial cells on wounds or burns. But those single layers are much simpler than trying to create actual skin, which is multi-layered, uses diverse types of cells and has a network with blood vessels that can be attached to a recipient’s vascular system. If multi-layers of living cells are printed, the interior level(s) of cells die as they quickly become starved of oxygen and nutrients and have no way of removing carbon dioxide and other waste. Cells must be within 150 to 200 microns of the nearest capillary to survive. Researchers at the Harvard School of Engineering and Applied Sciences (SEAS) and the Wyss Institute for Biologically Inspired Engineering at Harvard University have recently revealed a technique they’ve developed to try to overcome the vascularization issue using a unique ink that dissolves while those around it solidify, created an interconnected network of hollow tubes. The Harvard team has tested the method on 3-D constructs with blood vessels and injected human endothelial cells into the vascular network, resulting in the cells regrowing the blood-vessel lining. Further testing is necessary to confirm the the constructed vascular network can be connected to natural vasculature.
Researchers are still years away from being able to create vascular/capillary networked living tissue with the cell density and size of a human organ. Ironically, the heart will probably be much easier to construct than some other organs, especially those dealing with biochemistry functions like the kidneys or liver. Each of those organs has dozens of types of cells, making the idea of Bioprinting a billion-plus cell organ that much more daunting.
Then there is the nerve cell issue. When it comes to 3-D printing of nerve cells, there are two different end goals. The first goal and the one that will hopefully be accomplished in the near future is the development of patient-specific 3-D conduits that could be inserted between severed nerve cells to reestablish connection. This would have obvious implications in the treatment of spinal paralysis victims and those suffering from nerve degenerative disorders. In December of 2013, the Biofabrication Journal reported that UK scientists had successfully printed retinal ganglion cells and glial cells for the first time. This marks the first 3-D printing of cells derived from the central nervous system. The scientists plan to print other cells of the retina and to investigate if light-sensitive photoreceptors can be successfully printed using their technique. If successful, this could ultimately lead to an effective treatment for Macular Degeneration, a major cause of blindness. Also, researchers at the Australian National Fabrication Facility (ANFF) have also reported success in the creation of 3-D conduits that can be inserted between damaged or severed nerves and used to grow new, reconnected cells.
The second goal and one which seems much further down the road is the ability to 3-D print the neural paths/receptors into 3-D printed organs so as to enable them to correctly interface with the recipient’s peripheral nervous system (PNS) and autonomic nervous system (ANS). This adds several levels of difficulty to the previously mentioned challenges of organ production and will likely be many years down the road before such a intricate system could be printed. Perhaps an interim step will be the used more successfully. The Wake Forest Institute for Regenerative Medicine is one of the pioneering institutions that combines bioreactors that grow human tissue and organs with 3-D Bioprinting.
But the technology does not have to get to the level of full production of working organs to be useful in healthcare. According to a January 2014 Forbes report, doctor’s at Louisville’s Kosair Children’s Hospital were able to print a 3-D model of a 14-month-old child’s heart that had been born with a unique defect. In less than 24 hours, the hospital was able to print a 3-D model of the defective heart which enabled the doctors to extensively study the defect and come up with the corrective procedure that saved the child’s life. This is not the only recent example of using 3-D Printing to produce incredibly accurate models of biological structures. Yale neuroscientist Gordon Shepherd of the Yale Center for Engineering Innovation and Design (CEID) recently produced a 4.25 inch x 5 inch 3-D model of a neuron, exact in every way other than size. The researchers believe the 3-D modeling will lead to new insights and discoveries as scientists are able to better visualize the complicated 3-D architecture of the brain’s microcircuits.
Hardware and Software Advances: 3-D Printers have actually been around for decades. But they were very large industrial-sized machines that used very expensive 3-D CAD software and were mainly limited to large corporations that used them for prototype development. But several changes have occurred over the past year or so that have the industry set for major growth. On the hardware side, the machines have significantly dropped in size and in price. Most of the 3-D printers use some variant of ink-jet technology to deliver the “ink”. For those involved in Bioprinting, they must customize the printer to incorporate cartridges capable of holding and sustaining living cells and modify the print heads to deliver the cells. Many 3-D printers use one arm with multiple heads to print multiple materials one after the other. But a University of Iowa device has multiple arms that can print several materials concurrently. This advance could be a faster option for bioprinting because one arm can be used to create blood vessels while the other arm is creating tissue-specific cells in between the blood vessels.
The actual delivery of the cells as the printer is working involves careful consideration of the viscosity and surface tension of the cell-laden fluid, sometimes referred to as “Bio-ink”. Correct delivery speed and concentration is just as important as positioning. There is not, as of yet, an industry-norm as to what liquid medium is used to hold and convey the cells but several institutions have revealed information on the makeup of their “Bio-ink”. The Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB) in Stuttgart, Germany recently gave details on their gelatin-based Bio-ink. This could be the ideal medium as Gelatin, a derivative of collagen, is one of the main constituents of human tissues.
The ink-jet printing technique used by most researchers tends to leave a significant percentage of the printed cells damaged or dead. A recent development by the Houston Methodist Research Institute uses an alternate delivery method they call BloC-Printing that manipulates microfluidic physics to guide living cells into hook-like traps in a silicone mold, resulting in a almost 100% survival rate of the living cells. This method cannot as yet produce multi-layered structures so it is unknown whether it will ultimately end up being feasible for more complex Bioprinting.
On the software side of Bioprinting, an explosion of much lower cost 3-D modeling software has matched the drop in hardware prices to make it much more affordable for institutions to look into developing uses for 3-D printing where they might have in the past thought it outside their budget. Also, a key patent for ultrahigh-resolution 3-D printing technology expired in January, 2014. The technology, known as “Selective Laser Sintering” will soon allow consumer-grade 3-D printers to create complex 3-D creations that were previously limited to expensive industrial-grade 3-D printing. The technology uses a high-powered laser to enable the fusing of plastic, metal, ceramics and other materials into a physical object, one layer at a time.
And another recent advance is the availability of much more affordable 3-D scanners, which use fixed or sweeping lasers to capture the 3-D geometry and color data of an object. This drastically reduces the development time but has, up until recently, been a very expensive add-on technology. These scanners have the potential to increase the speed and affordability in the 3-D printing of custom appendage prosthetics, ears, spinal discs, heart valves, bones and facial prosthetics.
All of this adds up to some significant advancements in healthcare-related 3-D printing over the past 12 months or so. Suddenly the long-sought abilities to repair serious spine injuries, blindness and other serious health issues that have previously been beyond our medical capabilities are seemingly close to being within our grasp. Much like the Internet boom of the 90s, there are many start-ups eager to use 3-D printing in the healthcare industry in new and innovative ways. No one can know exactly where 3-D printing is going and what its ultimate limitations might be. But those at the forefront of the technology are already testing technologies that just a decade ago would have sounded like science fiction.
Barbara Lorber, Wen-Kai Hsiao, Ian M Hutchings, Keith R Martin. Adult rat retinal ganglion cells and glia can be printed by piezoelectric inkjet printing. Biofabrication, 2014; 6 (1): 015001 DOI: 10.1088/1758-5082/6/1/015001
Author: Ed Ruth writes about politics, health and science