According to a recent report, “Applications of 3D Printing 2014-2024: Forecasts, Markets, Players,” “The global 3D printing market will reach at least $7 billion by 2025, which includes a conservative estimate of $3 billion for bioprinting.” The ability to create three-dimensional (3D) models and prototypes has enabled advancements in many industries. As the use of 3D printing grows overall, the use of 3D printing and 3D bioprinting in healthcare applications is also increasing.
3D Printing Applications in Healthcare
3D printing and 3D bioprinting have the potential to revolutionize healthcare. 3D printing, also called additive manufacturing, is the process of creating a three-dimensional (3D) model by laying down successive layers of material that build upon each other. Printing materials or “ink” can be a variety of substances including plastics, polymers, metal alloys, among others. When the ink being used is living cells, the 3D printing is called 3D bioprinting. Both 3D printing and 3D bioprinting are increasingly being used to advance healthcare. I have highlighted some examples of both 3D printing and 3D bioprinting and their corresponding applications in healthcare.
A Personalized Approach
A recent New York Times article, “Off the 3-D Printer, Practice Parts for the Surgeon,” gives an example of the powerful use of printing 3D models for surgery. In the New York Times example, a surgeon was able to create 3D plastic models of a child’s skull prior to surgery. The child had been born with the rare defect, Tessier Facial Cleft that caused a fissure in her skull. The surgeon was able to use MRI images to create 3D models to help him plan and practice the surgery in advance and to consult during the surgery. These 3D models are increasingly being used to assist surgeons and are being credited with shortened surgery times and improved outcomes.
Another example of 3D printing being used to model patient conditions for a personalized approach was discussed in the Reuters article, “3D printing points way to smarter cancer treatment.” In this example 3D models of cancerous tumors and the surrounding tissues are printed using CT scans for reference. Doctors are then able to run liquid through the model to visualize the flow of radiopharmactuicals. “Radiopharmaceuticals are drugs containing radioactive material that may be injected into a vein, taken by mouth or placed in a body cavity. The challenge is to give a dose that is high enough to kill cancer cells, without causing excessive collateral damage to healthy tissue.” By using this method, doctors are hoping to more effectively target tumors and deliver the proper dosage, while reducing toxic effects and ultimately providing better outcomes.
Another emerging area for the use of 3D printing is in the printing of customized implants for patients. Although limited now, there is some implementation in creating dental implants and implants for use in orthopedics. One life saving example of a customized implant was detailed in the article, “Baby’s life saved with groundbreaking 3D printed device from University of Michigan that restored his breathing.” In the article the author describes how researchers at the University of Michigan created a custom external airway splint to save the life of a child born with tracheobronchomalacia (TBM). With TBM there is an excessive collapse of the airways that prevents proper respiration. The splint was created using 3D printing and was made out of material that is reabsorbed by the body; the device will prevent the life threatening compression and will allow the child to breath normally. For more information about this application, please see the journal publication in Science, “Mitigation of tracheobronchomalacia with 3D-printed personalized medical devices in pediatric patients.”
To see how the device is made at the University of Michigan using 3D printing:
3D Bioprinting in Healthcare
Drug Discovery and Product Development using Printed Tissue
Researchers have successfully demonstrated that they can use 3-D bioprinters to create living tissue including liver, cartilage, heart, and fat tissue. Organovo, a San Diego based company is currently using their NovoGen 3D bioprinting process to produce liver tissue for preclinical drug screening and toxicity testing. The process, described on their website, begins with a design of the tissue to be made, then they use bio ink, “multi-cellular building blocks used to build target tissue,” released from a bioprinter in a layer by layer building approach. In November 2014, they launched their exVive3D™ Human Liver Tissue for preclinical drug discovery testing. This product will allow companies to test drug candidates to discover potential liver toxicity and also ADME (adsorption, distribution, metabolism and excretion) outcomes.
According to their press release, the product is created using primary human hepatocytes, stellate, and endothelial cell types, all found in the human liver. The tissues are functionally stable for at least 42 days. This is important for pharma companies who would like to be able to use liver tissue for drug challenges and need to be able to test various doses in the same tissue over a period of time.
To see how Organovo prints their living tissue, please see:
In April, Organovo presented data on their in vitro 3D kidney tissue at the 2015 Experimental Biology conference. This provides another tool for drug discovery and in particular examining a drug’s toxicity to the kidneys. The printed kidney tissue is “multi-cellular and fully human, it consists of polarized renal proximal tubular epithelial cells and a living interstitial layer comprised of renal fibroblasts and endothelial cells.”
In May, Loreal and Organovo announced a partnership to utilize Organovo’s Bioprinting platform to create 3D printed skin tissue for Loreal’s product development and research. For over 30 years Loreal has been producing skin as a way to test products without having to use animal testing. It has lab facilities in France, where they grow skin samples from cells donated by plastic surgery patients. The partnership with Organovo, should enable more effective production of the skin samples they need. The partnership is covered in more detail in the Bloomberg article, “L’Oreal’s Plan to Start 3D Printing Human Skin,”
In the future there is also the possibility that Organovo’s platform could be used to print tissue for therapeutic applications.
Wake Forest has been developing a 3-D bioprinting application for burn wounds. They have developed a procedure that would take a scan of a burn wound and then the 3D bioprinter would directly print skin cells onto the burn wound in layers, which would replace where the damaged skin. Using the scan as a map, the printer can fill in the burn wound until it is covered with the new skin cells. The application is in clinical trials in mice. Please see this video for more details -http://www.wakehealth.edu/Research/WFIRM/Research/Military-Applications/Printing-Skin-Cells-On-Burn-Wounds.htm
Another example of bioprinting for therapeutic use was featured in the New York Times article titled, “At the printer, living tissue”. In the article Dr. Darryl D’Lima, who heads an orthopedic research lab at the Scripps Research Institute, describes how his group began using modified ink jet printers to print cartilage. He believes cartilage is a good fit for 3D bioprinting because chondrocytes secrete their own matrix, don’t need many nutrients and overall are pretty low maintenance. Their “bio ink” is made up cartilage cells and PEG-DMA that when printed under UV light has a gel consistency.
Printed Organs in our Future?
With 21 Americans dying daily waiting for an organ to become available for transplant, there is understandably a lot of interest in generating transplantable organs using 3D bioprinting. However, most experts believe that this kind of advancement is at minimum, decades in the future. In addition to more accessible organs, there are significant advantages in using bioprinting for manufacturing. One of the primary being that the organs could be generated using a sample of the patients’ own cells, thus limiting or eliminating organ rejection issues and corresponding treatments that carry negative side-effects.
Though organs are still several years in the future, there are many applications involving 3D printing and 3D bioprinting that will benefit patients now and in the near future. In addition to the applications described above, researchers are working on heart tissue to use as patches for repairing heart damage and fat tissue to repair damage done by breast lumpectomies.
As with any emerging technology, there are challenges associated with 3D bioprinting, particularly when a therapeutic application is the goal. One identified problem is how to keep bioprinted tissues nourished, particularly for transplant cases until the body can build the appropriate blood vessel connections. In some instances, these tissues are kept in well plates or bioreactors to maintain until ready for use. In other instances, tubes have been inserted as artificial blood vessels to provide nutrients until the structures could be incorporated into the body. There are also challenges with the mechanics of the printer meeting the needs of living cells. For more details, the Dish Guest Blog, “Bioprinting – Research Successes, Challenges, and Future Possibilities,” looks at specific challenges associated with 3D Bioprinting,
These initial applications are building proof of principle, safety and efficacy, which will pave the wave for future uses of this technology. Ultimately it is a long and complex journey for any potential therapies, but clearly an exciting new area of discovery.
For more information about 3D Bioprinting, there is an excellent Nature Biotechnology article – “3D bioprinting of tissues and organs,” by Sean V Murphy and Anthony Atala.
Do you know of any other applications of 3-D bioprinting? Please share in our comments section.