Much of the press for medical 3D bioprinting has revolved around recreating parts of the human body for medical transplants, implants, and reconstructive surgery. We often find these stories easy to relate to, with visuals that help us understand the benefits of each bioprinting solution.
However, another important aspect of bioprinting that may not be as obvious is its potential contribution to early-stage disease research. This type of research occurs in the laboratory, and focuses on how our cells (the tiny building blocks that make up every part of our body) function and interact during diseases. 3D bioprinting could present a step forward in how researchers construct experiments that help them understand disease.
One of the crucial steps to understanding each type of cancer is figuring out how it communicates with other cells, and what it is saying. Cells in a tumor may talk to cells from within the same tumor, or surrounding healthy cells, and all of this communication could be important for cancerous cells to grow and spread. Thus understanding how cells interact is an important step towards blocking this communication using medical treatments.
To easily set up experiments in the lab, researchers use cancer cell lines - cells which have been taken from tumors and trained to grow in the lab. These cell lines are grown in a single layer, and although this makes it easier to keep them happy, it is quite different to the way cells are arranged in our bodies, i.e. in multiple layers in a 3D space.
3D Bioprinting Cancer
With so many important functions of cancer due to the communication with other cells, it is beneficial for scientists to perform experiments on cancers that are as similar as possible to a living patient. Last year, researchers at the University of Connecticut and Harvard Medical School addressed this, published a review of 3D bioprinting focusing on its potential advantages for cancer research in the lab.
Cancers are a prime candidate for 3D bioprinting - many cancers exist as clumps of cells that lack specific structures, and thus do not require the typical scaffolding that bioprinting organs like ears or bones requires. By layering cells in 3D instead of 2D, a 3D printed tumor is better at replicating the structure of a tumor in a typical human body, and communication between cells in all directions can be achieved.
3D bioprinting also offers the possibility of mixing multiple cell types. This is important because cancer cells communicate not only with each other, but also healthy cells - for example, melanomas interact with surrounding skin cells. In fact, even within a tumor there may me multiple "versions" of cancer cells, all having different things to say each other. Since bioprinting multiple cell types is relatively simple, it is possible to recreate not only tumors themselves more effectively, but also their surroundings.
Current research already feeds into this, as there are already many different types of cancer cells available, and established techniques for getting them into a liquid form for 3D printing.
Customizable, reproducible experiments
It is incredibly important that the results of any research be reproducible, not only within a research group but also between research groups across the globe. Since bioprinting is done using 3D computer models, these can be easily distributed to other researchers. And with the ability to customize the construction of a tumor completely using bioprinting, scientists can validate their results and move faster to obtaining medical solutions.
One of the greatest challenges could be integrating 3D printing medical laboratory techniques that have been established for decades (the first cancer cell line was created in the 1950's). Luckily, companies like Biobots are capitalizing on this gap in the market, building accessible 3D bioprinters with standardized components. And repositories like Build With Life will hopefully hold not only bioprinting designs, but also important protocols that merge current medical research standards with 3D printing technology.
The utilization of bioprinted cancers could be important to the development of new medical treatments. By understanding the interactions between cancer cells and healthy cells in all dimensions, researchers can gain insights into the successful treatment of these cells. And all of the techniques mentioned above could be extended to a range of other diseases. Organovo has already capitalized on this idea, 3D printing liver cells for scientific testing.
One could even predict that, in the same way as 3D-printed organs of specific patients are being used to plan for surgery, 3D printed recreations of patient's tumors or diseases may be able to help tailor the most effective treatment for that patient. The future for integrating bioprinting into the workflows of laboratories around the world seems bright, and could offer faster and more accurate methods for carrying out early-stage research in cancer and many other diseases.
National Cancer Institute
Recently, the University of Texas Medical Branch at Galveston (UTMB) in conjunction with MakerNurse, John Sealy Hospital, and the Robert Wood Johnson Foundation, unveiled the first MakerHealth facility. This space was created to inspire nurses to creatively solve problems they see every day caring for their patients, using a diverse range of crafting tools, from zip ties to 3D printers. The initiative recognizes that many nurses are already coming up with creative solutions to problems with patient care, and aims to facilitate the DIY attitude. For example, one of the nurses has used his expertise in the burn care unit to devise a special showering unit for burn patients.
One of the most exciting concepts is that by providing this space, the hospital and University are supporting internal innovation. Too often nurses come up with extremely innovative ideas that are not captured - the nurses can be incredibly humble, believing that what they have done is the same as what anybody would do in their circumstances. By recognizing staff-driven innovation, the MakerHealth facility validates what nurses have been doing for decades and centuries - finding better ways to care for their patients. And hopefully this initiative will serve to connect these ideas with medical device companies who may lack the intimate connections to source such applied ideas themselves.
The accessibility of 3D printing to solve basic healthcare needs is a theme that has been mirrored in the utilisation of 3D printing for simple testing devices that assess patient diseases. Just last week, researchers at Kansas State University announced that they are developing a 3D-printed device that will be able to detect anemia (a condition where there is not enough iron in the blood) when connected to a smartphone. This development is building upon an already-growing repertoire, including devices that can assess eye health, detect sickle cell disease and cervical cancer, and read ELISA assays. The best part is the accessibility of these devices - most require only simple components a 3D printer, and a smartphone. The ease of putting these devices together can reduce the costs of healthcare, supporting poorer socioeconomic classes, regions, and nations.
All of the solutions described above are both influenced by and influencing the 'maker' mentality. A mentality driven by DIY attitudes, it is stretching healthcare to consumers as well - mobile healthcare is already a booming industry, with 52% of smartphone users gathering health-related information on their phones. The connections between smartphone and 3D printing technology mentioned above may mean that in the future, consumers will perform many tests themselves, perhaps as easily as one might conduct a pregnancy test. And if 3D printers become a common household item in a similar way to current home printers, it may be possible to perform these tests without having to leave the comfort of your own home. Thus 3D printing, smartphones and the maker mentality may result in a healthier population at a lower cost, less visits to the doctor, and more time for doctors to focus on complex healthcare issues.
This week cdmalcolm posted a great article here at Embodi3d.com on how 3D-printed replicas of patient’s organs are helping surgeons plan for complicated operations. Today I'd like to supplement this topic by talking about the advances 3D printing can bring to medical education, specifically by recreating human models for students to study and dissect.
Currently, the golden standard for teaching medical students the anatomy (overall structure) of the human body involves dissecting and observing cadavers – recently deceased humans who have given their bodies to science. However, obtaining and storing these bodies can be difficult for a number of reasons. For example, many cultural and religious beliefs preclude people from donating their bodies, and even in countries with strong donation programs bodies with rare diseases (by their very definition) are hard to find. Even when sufficient cadavers are donated, the process of preserving them to prevent natural decomposition can be costly.
New technology comprising a mixed approach of 3D printing and traditional manufacturing can solve many of these problems by recreating accurate and numerous replicas of human anatomy with minimal expense. A recent publication in the January/Februrary edition of the journal “Anatomical Sciences Education” highlighted a prototype for this technology; the team from The University College Dublin in Ireland were able to recreate a portion of the hip, with 3D-printed bone and blood vessels surrounded by a flesh-like filler and covered in a synthetic skin. On top of this, they were able to connect a pump to the blood vessels to mimic the typical human circulatory system. The result wasn't fancy - the components were placed in a Tupperware container with holes for the tubing - but it had most of the necessary components for students to learn, and more importantly, obtain valuable practical experience.
The advantage of using 3D printing for these models is that they can be changed to reflect the anatomy of specific diseases. For example, atherosclerosis occurs when blood vessels narrow, and it is an important factor in heart disease. In the prototype above, the team were able to 3D-print replicas of blood vessels from a healthy patient, and one with atherosclerosis - the vessels with atherosclerosis were a lot thicker, and students were able to assess this using ultrasound. The students were also able to perform basic techniques to locate the vessels via syringe, similar to how they may be required to set up an IV drip. And since the models only need to mimic the qualities of human organs rather than making functional tissue (see my previous article on the challenges of this), the models can be made relatively simply, and from materials that do not degrade over time like human flesh does.
It might seem like a reconstruction of the human body would never be able to replicate the experience of learning from a true human body, however the results of the study above and previous work by The Centre for Human Anatomy Education in Australia showed that 3D printed models are just as good as cadavers for teaching students the principles of anatomy. And thus the future of manufactured lifelike bodies for teaching seems bright - indeed, one could imagine that many trending technologies could be integrated with these models to provide teaching experiences that surpass the current standard delivered by cadavers. Digital sensors are rapidly becoming cheaper and more ubiquitous in technology, and these could be incorporated into anatomical models to provide feedback to students during practical tasks. Virtual reality (VR) and augmented reality (AR) are also trending with many potential application for medicine. Perhaps in the future, manufactured human anatomical models will be integrated with AR, in a way that replicates the experience of operating on real-life patients.
And so, 3D printing technology seems poised to replace the long-standing use of cadavers for medical education, and soon many medical students will be able to sigh with relief at not having to prepare themselves to touch and dissect decomposing, smelly bodies. The inexpensive production of realistic bodies will give students better access to practical hands-on education, better preparing them for their eventual roles dealing with real patients.
Scientists at the Wake Forest Institute for Regenerative Medicine in North Carolina, USA, have taken the next step towards printing living replacement parts for our bodies. In a study published in the February 15th edition of Nature Biotechnology, the scientists revealed the ITOP (Integrated Tissue-Organ Printer). This 3D printer, which has been in development for over 10 years, is able to form structured living tissue, including ears, bones and muscles, which look and function like the real thing.
One of the biggest hurdles currently for printing body parts involves giving them the right shape and structure, rather than just making a mass of biological goop. Unfortunately, human cells are extremely sensitive, and many of the components that a 3D printer could use to give structure are also toxic, preventing the replacements from living happily over the long-term. However, the team came up with a specific layering pattern incorporating two key pieces of technology.
The first breakthrough is the optimised layering of two scaffolding materials, with each material having a part to play in generating the final living structure. One of the materials is very strong but toxic, and gives the body part its overall structure during the printing process, before being washed away immediately afterwards. In the meantime, the second material has been held in place by the shell, and has had the time it needs to harden. This material gives long-term stability to the living tissue without toxicity. Eventually it will be replaced by the body part’s own secretions, making it just like those we can already find in our bodies.
The second key technology is the incorporation of empty tunnels within the layers. These allow the transfer of life-giving oxygen and nutrients throughout the living tissue. The team was able to 3D print an ear, small pieces of bone, and some muscle tissue. More importantly, all of these retained their structure, and carried out their basic functions. For example, the 3D-printed bone produced calcium, the ear produced cartilage, and the muscle rearranged itself into the proper structure for exerting force.
These beginning steps set the stage for the next phase in custom-printing replacement body parts. Many hurdles still stand between the ITOP and its use in healthcare, such as figuring out how well the body tolerates the 3D printed replacements. However the research of this team is a huge step toward printing living, functioning replacements for our bodies. And the advantage of 3D-printing compared to other techniques is the extreme level of control, both over the construction of the replacement, and the tailoring of each piece to suit the subject perfectly.