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Here is my video review of the Ultimaker 3 Extended for medical 3D printing. It was 4 months in the making. Medical anatomical models can be challenging to 3D print because of complex anatomy and large size. This 3D printer has a couple of features which help overcome these challenges.
- First, the Ultimaker 3 is a dual extrusion printer which allows for two different materials to be used during a single print. This video shows 3D printing with one water soluble material for support and another material for printing anatomical structures. I show how water soluble PVA provides support during the build and can be easily dissolved in tap water once the build is complete.
- Second, the Ultimaker has a large build volume compared to most 3D printers in this price range. This allows for anatomical structures to be created in one print rather than having to do several prints and putting the pieces together.
While there are several good features of this 3D printer, there is still room for improvement. In this review I successfully 3D print small structures like a vertebra, but struggle with large and more complex structures like human brain and lumbar vertebrae. Watch this video review and follow along as I provide the pros and cons of medical 3D printing with the Ultimaker 3 Extended.
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Many doctors these days are now including 3D printing as part of their many surgical procedures. Dr. Jamie Levine from NYU Langone noted that there is a paradigm shift when it comes to doing surgical procedure in terms of using and relying on 3D printing.
A lot of hospitals all over the United States have already embraced 3D printing to create tools, models or craft tissues used for surgery. One of the hospitals that are leading the paradigm shift is the Institute for Reconstructive Plastic Surgery at NYU Langone. The surgeons from NYU Langone use special printers to create tools and 3D models that can save doctors from performing long and expensive surgeries. In fact, the hospital is able to save $20,000 to $30,000 for every reconstruction that the do.
The use of 3D printing in medical technology is very promising. In fact, the Food and Drug Administration has already approved the creation of 3D printed pills and vertebrae. There are also many researchers all over the world working with 3D printed organs to be used in organ transplantation.
Although medical-grade 3D printers still remain expensive, they can make infinite types of objects like surgical tools, anatomical models and other devices. Fortunately, there are now many companies that are developing cost-effective printers thus the cost is targeted to go down in the future.
There is a wide potential for innovation when it comes to using the 3D printing technology. With this technology, it is no wonder if many hospitals all over the world will rely on 3D printing technology to treat different diseases.
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A neurosurgeon from Saskatoon in Canada has 3D printed a replica of a patient’s brain to help him plan a complex medical procedure.
Working with a team of engineers, Dr. Ivar Mendez created an accurate replica of the patient’s brain, which will allow him to practice surgery.
Dr. Mendez is the head of surgery at the University of Saskatchewan, and is already familiar with using advanced technologies to improve surgical results. He uses computers in the operating room, and has a medical engineer as part of his surgical team.
However, putting together a 3D brain was a more complicated task, but it would make it possible for him to practice working on some of the smallest components of a brain.
"You can imagine it as having a pea inside a sock or balloon," Mendez told CBC. "It is a complex system.”
What makes the model so valuable is that it’s an exact replica of the patient’s actual brain. If they have a tumor or other abnormality, Mendez and his team can create a replica that includes these unique features.
The patient in question was planned to undergo deep brain stimulation. Dr. Mendez needed to insert electrodes into the brain to help soothe overcharged neurons. He usually plans this kind of surgery using a computer model, but wasn’t successful in this case.
His idea was to position one electrode to affect two target neurons, but the computer model wasn’t capable of this kind of surgical planning. Human brains are particularly complex, which makes it difficult for computers to predict how the tissue will react to certain tools.
“I wanted a way to really, before I did a surgery, to know exactly how this was going to reach the brain and the targets I wanted,” Mendez told The Star Phoenix.
That’s why Mendez decided to team up with the school of engineering at U Saskatchewan, as well as radiology technicians and a neuropsychology specialist. The team worked together to make the MRI data understandable to the 3D printer.
The 3D model took 7 months of planning before a prototype was created. It was printed using a transparent material similar to rubber, that allows surgeons to see all the internal structures of the brain as well. Mendez said it also feels fairly similar to an actual human brain.
"I'm a neurosurgeon but I'm also interested in art. To me, this was an object of beauty,” he said.
Dr. Mendez believes the development of the technology will bring new opportunities for surgical practice.
"I envision that in the future we may be able to do procedures that are very difficult or impossible today," he said. "I feel that in the next 20, maybe 25 years, we will be able to print biological materials. We may be able to print organs."
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It seems that there is no end to the animals that will benefit from 3D printing and now the process has become so common place it is child’s play. Stumpy came to the Oatland Island Wildlife Center in Savannah, Georgia with a bad infection to his right front leg. In order to save the 12 year old box turtle veterinarian Lesley Mailer amputated the leg. Stumpy lived, but had a very hard time getting around without his front leg. Luckily for Stumpy, Lesley Mailer remembered her daughter mentioning a 3D printer that her 5th grade class at May Howard Elementary was working with. So Mailer contacted the school about creating a new leg for Stumpy.
The school took up the call and choose a few students who were interested in 3D printing and/or animals to work on the project. Six students and a teacher went to work right away to learn about box turtles to understand what Stumpy needed in a new leg. The students were eager to learn and help Stumpy, they spent time after school and during their lunches to design the new leg. Using 3DTin to create 15 prototypes over a month of development the students created a leg that they thought would work for Stumpy. Mailer was just as excited as the students and invited all of them to watch as Stumpy was fitted with his new leg. With just a few minor alterations, Stumpy’s new leg fit perfectly. Now this little box turtle can live out the next 20 to 30 years moving around just as easily as any other turtle. But that doesn’t mean these dedicated students are taking a break, they intend to improve upon their design this year.
Main Image Credit: www.3dprint.com
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The Coalition for Imaging and Bioengineering Research (CIBR) is a dedicated partnership of academic radiology departments, patient advocacy groups, and industry with the mission of enhancing patient care through advances in Biomedical Imaging. My good friend and colleague Dr. Beth Ripley and I recently participated in the sixth annual Medical Technology Showcase at Capitol Hill organized by CIBR, representing the Department of Radiology at the Brigham and Women’s Hospital (BWH) where we emphasized the importance of 3D printing in healthcare.
The annual Medical Technology showcase aims to bring examples of medical breakthroughs in imaging and bioengineering to members of congress and demonstrate how these advances are impacting patient care. In addition to educating policy makers and the public about innovative imaging technology, the event demonstrates the value of NIH funded academic research and the importance of collaborations between academia, industry and patient advocacy groups.
Our display booth comprised of the Department of Radiology at BWH, the Lung Cancer Alliance, and Fujifilm was a hit among attendees and we were pleased to see the level of interest in medical 3D printing. We displayed 3D printed models that have been used for different clinical applications and our booth partners from Fujifilm demonstrated Synapse 3D, a software that allows conversion of 2D image data from CT/MRI into 3D printable files.
Our goal was to demonstrate the importance of 3D printing in pre-surgical planning and how it can benefit patients by allowing surgeons to devise a patient specific treatment strategy and minimize post-surgical complications. Sheila Ross, a lung cancer survivor and patient advocate from the Lung Cancer Alliance emphasized how 3D printed models can give patients and their families a better understanding of the planned procedure.
A lung model from Fujifilm demonstrating a nodule (green) and surrounding bronchioles
The Lung & Brain cookies might have been slightly more popular than our 3D models
It is our hope that more funding and resources will be allocated to investigate innovative medical technologies such as 3D printing, which can then be translated to impact patient care. In order to transform 3D printing from being a fad, to a mainstream tool that fosters precision medicine, evidence based benefits of its different applications will need to be demonstrated in clinical trials which will require funding.
Tatiana Kelil, MD
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Nice review paper on Medical Applications for 3D Printing: Current and Projected Uses:
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Very few infectious diseases in recent years have commanded the kind of attention and concern that Zika Virus has. Although Zika outbreaks have been reported in Africa, Southeast Asia and other parts of the world since the 1952, recent announcement by the Center for Disease Control and Prevention (CDC) confirming its link with microcephaly has forced everyone to sit up and take notice. The CDC estimates that the current pandemic is widespread with at least 50 countries reporting active Zika transmissions at this time. Most people with Zika virus infection will not have any symptoms though some may experience mild fever, conjunctivitis, muscle and joint pain, and headaches.
The virus is primarily transmitted by the Aedes mosquito. However, pregnant women may pass the infection to their babies, which may lead to microcephaly, a neurological condition associated with an abnormally small brain in the infant. The condition can lead to birth defects ranging from hearing loss to poor vision and impaired growth. Prompt diagnosis and treatment of Zika virus infections in pregnant women can, nonetheless, lower the risk of microcephaly to a great extent. Researchers have, therefore, put in a lot of time, money and effort to find a solution, and as always, three-dimensional (3D) medical printing and bioprinting technologies are leading the way.
Understanding the Disease
To begin with, 3D printing has played a crucial role in conclusively establishing the link between Zika virus and microcephaly. Researchers at John Hopkins Medicine used 3D bioprinting technology to develop realistic models of brain that revealed how the virus infects specialized stem cells in the outer layers of the organ, also known as the cortex. The bioprinted models allowed researchers to study the effects of Zika exposure on fetal brain during different stages of pregnancy. The models are also helping the scientists with drug testing, which is the obvious next stage of their research.
Zika Test Kit
Engineers at Penn’s School of Engineering and Applied Science, under the leadership of Professor Changchun Liu and Professor Haim Bau, have developed a simple genetic testing device that helps detect Zika virus in saliva samples. It consists of an embedded genetic assay chip that identifies the virus and turns the color of the paper in the 3D printed lid of the device to blue. This can prompt healthcare professionals to send the patient for further testing and to initiate treatment. Unlike other Zika testing techniques, this screening method does not require complex lab equipment. Each device costs about $2, making Zika screening accessible to pregnant women from the poorest parts of the world.
The scientists at the Autonomous University of the State of Morelos (UAEM) in Mexico are relying on the additive printing technology to create a microvalve that may help treat microcephaly in infants. The valve reduces the impact of the neurological disease and slows its progression by draining out excessive cerebrospinal fluid associated with this disorder. It can be inserted into the infant brain through a small incision to relieve fluid pressure and provide space for normal development. Researchers estimate the device will be available for patient use by 2017. These examples clearly demonstrate the impact of 3D printing on every aspect of the fight against Zika virus from diagnosing the disease to treating it. The results have been extremely promising, and both researchers and healthcare professionals are immensely hopeful that additive printing technology will help them overcome the infection quickly and effectively.
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Medical Three-dimensional (3D) printing has a variety of uses and is becoming an integral part of dentistry, oral surgery and dental lab workflows. 3D printing in dentistry is the natural progression from computer-aided design (CAD) and computer-aided manufacturing (CAM) technology which has been used for years by dental labs to create crowns, veneers, bridges and implants. Now, 3D printing is taking its place with 3D printing solutions for dental, orthodontic, and maxillofacial applications. Several 3D printer manufacturers, including Stratasys and EnvisionTEC, offer specialized materials and printers as part of their dental 3D printing solutions. Anyone can create 3D printed dental models and embodi3D has created a dental 3D printing tutorial which guides readers through the process of 3D printing teeth and mandible.
What is Dental 3D Printing?
Three-dimensional printing begins with a special scanner. The mouth of the patient can be scanned using contact or non-contact scanning technology. The device works by creating a super accurate, patient specific digital image of a dental surface that is then saved as a computer file. Using specialized software, the scan is translated into a 3D digital representation. The resulting digital model may be a tooth, several teeth or the jaw. This digital imaging is not only replacing CAD/CAM technology, but it is also replacing some of the old plaster impressions traditionally used.
Once the scan is complete and a 3D image has been created, the specialized software will prepare it for physical model creation. There are two popular methods for creating a physical model from the digital representation.
- The first method involves using a technique called slicing. With the help of specialized computer software, the original three-dimensional image is divided into thin horizontal layers. These layers are then transmitted to the 3D printer. The physical model is then printed layer by layer until the physical 3D model is complete.
- The second method is CNC milling. In this case, the complete digital image is transferred to a milling machine. Rather than print a model layer by layer, the milling machine starts with a solid piece of material. The machine then carves the new 3D physical model out of that block of material.
As techniques become more advanced, 3D models become more accurate and the technology becomes more readily available, the first method is used more often in dental diagnosis, treatment planning and construction of dental appliances such as dental implants, orthodontics, denture bases and bite guards.
Advantages of 3D Printing Teeth, Crowns, Dentures and Other Dental Anatomy
3D imaging has been used in dentistry for many years, however, the traditional method of model creation involves dental plaster models. While these models are accurate, so are 3D printed oral models. In fact, dental 3D printing is not only accurate, it is quick and a lot less messy. Patients who have undergone fitting for a crown or other dental appliance generally do not remember the process fondly. Plaster is messy and it has been necessary for patients to be fitted with a temporary appliance only to return for a second visit. This is both inconvenient and time-consuming. 3D imaging and printing can alleviate this problem. In dental offices with the capability, the process is fast and patients can often be fitted with their permanent appliance in a single visit without the plaster mess. This makes the entire process far more convenient for patients.
Dentists also benefit from 3D printing and imaging. Imaging files are far easier to store than bulky plaster casts. By going digital, dentists and maxillofacial surgeons can store patient information indefinitely. This makes it easier to refer to files time and again for comparison, planning and treatment.
As the 3D printer technology becomes more accessible, the cost of use is going down. Patients can have these procedures performed at prices comparable to traditional methods, and these costs will continue to decrease as 3D printer prices decrease.
Advances in 3D printing technology are constantly improving. Whereas manual creation of implants, crowns and prosthetics required a high degree of specialization, 3D printing can quickly and easily create highly accurate models. This provides better fitting, more personalized appliances improving both comfort and efficacy of prosthetics.
3D Printing in Maxillofacial and Oral Surgery
Maxillofacial and oral surgery is an area where 3D printing is currently being utilized for a variety of reasons including cancer, birth defects, injury or receding bone. Corrective surgery is often needed in cases like these. A prosthesis, implant, dental mesh, surgical stent and more can be created through the 3D scanning and printing process to aid patients.
In addition to creating the actual prosthetics, three-dimensional printing is also helpful as part of the planning process. Three-dimensional printing can be used to create prototypes of the planned devices prior to surgery. Having the ability to simulate devices prior to implantation can help surgeons work out complex reconstructions and ensure that devices fit well. This allows the entire surgical process to be safer and easier.
3D Printed Dental Implants
As with maxillofacial surgery, 3D scanning and 3D printing improve the fit, comfort and ease of dental implant surgery. 3D scans of the patient’s teeth, gums and jaw allow dentists to have a high degree of accuracy and as a result 3D printed dental anatomy is patient specific. There are many advantages to using 3D printing for dental implant surgery including:
- Determine depth and width of bone
- Accurate sizing for implants
- Determine the location of sinuses and nerves
Three dimensional printing creates accurate models that ensure a good fit. It is used to address issues such as location, angle and depth of the implant prior to surgery. This same technology allows dentists to create templates and surgical drill guides for permanent implants. Many dentists use these guides to improve surgical safety as they guide the surgeon’s hand, ensure correct placement and restrict the depth of the drill.
How 3D Printing is Used for Crowns
With 3D scanning and printing, dentists and patients can forgo the plaster dental mold and the need to rely on a lab for crown creation. With 3D technology, dentists can use a scanning camera and specialized software to create an exact three-dimensional image of the tooth that needs to be crowned if the tooth has not broken below the gum line. This image is then transmitted to a 3D printer or milling machine that carves a porcelain crown to exact specifications. The entire process can be completed in about an hour allowing patients to leave the dental office with a permanent crown on the same day.
Three-dimensional imaging is one more tool in the dentists’ and oral surgeons’ arsenal to provide better oral health care. With three-dimensional imaging and printing, dentists can gain more complete information for diagnosis and treatment, ensure safer procedures and provide a more comfortable fit for oral devices.
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Every 3D printing case is different, and must be tailored for the individual patient’s specific clinical condition, anatomy, and imaging techniques.
A 47 year old woman with a renal mass was being evaluated for surgical treatment planning. A urologist familiar with my current 3D printing work requested a 3D printed model of the kidney. The purpose was to help demonstrate the anatomy of the mass with respect to the renal hilum, to help determine if a partial nephrectomy was possible, or if a total nephrectomy was required.
The patient had a documented reaction to radiographic iodinated contrast, and therefore an MRI was performed instead of a CT scan. The scan was performed on a 1.5 T GE Signa Excite system. The data set from a coronal 3D gradient echo pulse sequence acquisition was chosen because it best visualized the tumor encroachment into the renal sinus.
The 3D model was created from segmentation of the kidney from the 3D gradient echo acquisition. The renal parenchyma was then made into the digital 3D model, leaving the mass as negative space. This was then printed to demonstrate the entire kidney. An additional 3D model was created showing a bisected view of the kidney along the coronal plane. This was done to see which model would be of more utility.
The patient’s DICOM image files from the MRI were processed using the Materialise Innovation Suite’s Mimics and 3-matic software.
Initially I used the Mimics software segmentation tool to segment the normal renal parenchymal tissue. This left a filling defect where the mass was. This negative space was useful for demonstrating the extent of the tumor.
Using the 3-matic application I then took the 3D digital representation and created a model cut in the coronal plane. This helped better define the extent of the tumor invasion into the renal hilum.
Both the full kidney and the coronal bisected models were printed for the surgeon and the patient to review. The STL (stereolithography or standard tesselation language) files generated for the 3D models were then imported into both the Cura and MakerBot slicing software applications to generate the gcode for the Ultimaker 2 and .x3g file for the MakerBot printers.
Fused filament printing of the full kidney using Acrylonitrile Butadiene Styrene (ABS) on the MakerBot Replicator 2X Experimental Printer and sectioned kidney in Polylactic Acid (PLA) on the Ultimaker 2 printer.
In general I prefer PLA to ABS. With PLA there is less shrinkage and warping of the material during the printing process. PLA is of plant based origin (here in the US it is derived from corn starch) and can print lower layer height and sharper printed corners. PLA, a biodegradable plastic is used in medical devices and surgical implants, as it possesses the ability to degrade into inoffensive lactic acid in the body.
ABS is a petroleum-based recyclable non-biodegradable plastic. Unfortunately emits a potentially hazardous vapor during printing. The Replicator 2X however is optimized for ABS. http://pubs.acs.org/doi/pdf/10.1021/acs.est.5b04983
For more information about PLA/ABS see http://3dprintingforbeginners.com/filamentprimer/#sthash.p07fHBmh.dpuf
The urologist showed the models to the patient, and it help to convince her of the necessity of a total nephrectomy, rather than a partial nephrectomy.
Although the printed models showed the extent of the tumor invasion adequately for both the urologist and the patient to visualize, the models did not differentiate the mass from the renal sinus.
To better demonstrate the tumor invasion, a new model with two different color filaments was created. Hand segmentation of the 3D model of the mass was performed due to the limited tissue contrast between the mass and the surrounding soft tissue structures. Creation of two separate segmentation files and 3D models was made in Mimics.
This was then exported into 3-matic for local smoothing. Two separate STL files of both the mass and kidney were generated. The combined model was then bisected in the coronal plane and the additional two STL files were again generated.
Once the combined STL files were imported into the MakerBot software, they were repositioned on the build plate in an orientation to optimize the printing process. The STL models were positioned on the bed, above a ring spacer file. This is necessary for the proper printing contact. The model was oriented to minimize the amount of printing support structures.
When using the two filament colors, “purge walls” are generated by the software to help eliminate the small threads of filament from one color being deposited when the next color is laid down.
The two filament model enables the surgeon and the patient to better visualize the extent of the tumor invasion, clearly demonstrating normal from abnormal tissues.
Harvard University researchers have 3D printed the first organ-on-a-chip with integrated sensors. This new technology could revolutionize the biomedical research field, which has relied on expensive and time-consuming animal studies and cell cultures for decades.
Organs-on-chips, or microphysiological systems (MPS), are microchips that recapitulate the microarchitecture and functions of living human organs in vitro. The Wyss Institute at Harvard University explains MPS as follows: “Each individual organ-on-chip is composed of a clear flexible polymer about the size of a computer memory stick that contains hollow microfluidic channels lined by living human cells interfaced with a human endothelial cell-lined artificial vasculature, and mechanical forces can be applied to mimic the physical microenvironment of living organs.” Typically, MPS are made in clean rooms using a complex, multi-step lithographic process. Collecting data requires microscopy or high-speed cameras.
What makes this new MPS different, is the simplified manufacturing process and the integrated sensors. Both improvements were accomplished with multi-material 3D printing. The researchers designed six “inks” that enable integration of sensors. The researchers successfully 3D printed a heart-on-a-chip with integrated sensors. They then used the heart-on-a-chip in various studies, including drug responses. The integrated sensors enable continuous data collection, allowing scientists to study gradual changes over longer periods of time.
Read the research published in Nature Materials or watch this video to learn more:
Photo and video credit: Wyss Institute for Biologically Inspired Engineering at Harvard University
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This a video demonstrating the use of Mimics software to convert patient dicom images into 3D printable files. Mimics software has many great features to improve and ease workflow. Like other software programs most segmentation and exporting can be accomplished in 15 minutes.
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According to the US Department of Health and Human Services, 22 patients die each day in need of an organ transplant because the demand for organs far outpaces the supply. If the compelling idea of producing 3D printed organs is realized many lives could be saved.
A big challenge in this field is to produce printable material that can support cells and is also permeable to nutrients. A hydrogel is a type of synthetic cross-linked polymer that is highly water absorbent. Hydrogels are commonly used as tissue engineering scaffolds for cells because of their biocompatibility.
This is a hot topic in the field right now, and many people around the world are working on developing new bioprinting methods. A challenge to the development of these methods is how well the printed object corresponds to the plan.
A group of Chinese scientists did a study of how various printing parameters affected printing fidelity. They published their results last week in Scientific Reports, the premier scientific journal Nature brand’s open source online journal.
The printing material or bioink must be liquid before printing and gel after printing. To make their hydrogels, they used sodium alginate (the same material this group used to print vasculature), gelatin, and a solution of calcium chloride as a cross linker.
In order to develop a bioprinting process, they feel it is important to understand the impact of changing the printing parameters including air pressure, temperature, feed rate, and printing distance. Another parameter included the ratio of gelatin and alginate.
Using a lab-built 3D printer, they started out with printing 1D lines on a flat surface, connected at different angles. They moved on to lattice shapes as shown in the image above, looking at how well the lattice maintained its shape with different line spacings. The hydrogel tends to spread somewhat upon printing. The printing surface was cooled so that the gel formed. The experiments also determined the impact of gravity.
They used extrusion based printing as opposed to other types of printing because cells are sensitive to thermal and mechanical stress. They found that the 3D printing process did not damage or kill mouse fibroblast cells suspended in the hydrogel as it only had a slight impact on cell survival.
Finally, the looked at a 3D object with successive printed layers as shown in the figure below.
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3D printing has been integrated into the surgical procedures of many physicians, as it has proved very useful in the planning stages of a surgery. It allows doctors to operate with more accuracy and precision by providing a means for surgeons to become acquainted with three-dimensional models of their subjects beforehand.
These models provide a holistic view of the part of the body under examination, which affords the surgeon time to assess the model and make changes in their surgical procedures or recommendations as required. Furthermore, viewing a 3D representation is far superior to that of a CT scan or MRI, as those technologies use flat images that are often difficult to read. A 3D model provides a more realistic view of the subject that is easier to understand. This ultimately gives the surgeon a greater understanding of the anatomy and allows practice before attempting surgery.
Dr. John Meara, plastic surgeon-in-chief at Boston Children's Hospital explained to the Boston Globe that, “In the past, sometimes you had to make many incisions in the operating room. Now I’m making those decisions on a model ahead of time.” By doing this, the doctor is able to reduce operating time and improve recovery time as the patient’s body experiences less trauma during surgery.
Before surgery, the 3D model can also help communication with patients, as the doctor can use the model to explain exactly how the procedure will take place. This increases the patient's trust and further improves the medical care and attention received by the patient.
Affordability Contributes To Increasing Medical Use Of 3D Printing
Surprisingly, 3D printing systems are not as expensive as one would think, and in fact are quite affordable, starting as low as a few thousand dollars for a basic 3D printer. Naturally, more sophisticated models fetch a higher price, but overall the cost of this technology is not insurmountable. This presents the opportunity for 3D printing systems to be used on a wider scale, and ultimately become as common a tool in the medical field as a stethoscope.
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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.
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Here is a tutorial for the Grayscale Model Maker in the free program Slicer, specifically for modeling pubic bones since they are used in anthropology for age and sex estimation. The Grayscale Model Maker is very quick and easy!
And I can't stand the "flashing" in the Editor.
Slicer Functions used:
- Load Data/Load DICOM
- Volume Rendering
- Crop Volume
- Grayscale Model Maker
Load a DICOM directory or .nrrd file.
Make sure your volume loads into the red, yellow, and green views. Select Volume Rendering from the drop-down.
Select a bone preset, such as CT-AAA. Then click on the eye next to "Volume."
...Give it a minute...
Use the centering button in the top left of the 3D window to center the volume if needed. Since we only want the pubic bones, we will use the ROI box and Crop Volume tools to isolate that area.
To crop the volume check the "Enable" box next to "Crop" and click on the eye next to "Display ROI" to open it. A box appears in all 4 windows. The spheres can be grabbed and dragged in any view to adjust the size of the box. The 3D view is pretty handy for this so you can rotate the model around to get the area you want.
The model itself doesn't have to be perfectly symmetrical because you can always edit it later. Once you like the ROI, we can crop the volume.
To crop the volume, go to the drop-down in the top toolbar, select "All Modules" and navigate to "Crop Volume."
Once the Crop Volume workspace opens, just hit the big Crop button and wait. You won't see a change in the 3D window, but you will see your slice views adjust to the cropped area. At this point, you can Save your subvolume that you worked so hard to isolate in case your software crashes! Select the Save button from the top left of the toolbar and select the .nrrd with "subvolume" in the file name to save.
Now we will use the All Modules dropdown to open the Grayscale Model Maker. If you want to clear the 3D window of the volume rendering and ROI box, you can just go back to Volume Rendering, uncheck the Enable box and close the eyes for the Volume and ROI.
When using the Grayscale Model Maker, the only tricky thing here is to select your "subvolume" from the "Input Volume" list, otherwise your original uncropped volume will be used.
Click on the "Output Geometry" box and select "Create a new Model as..." and type in a name for your model.
Now move down to "Grayscale Model Maker Parameters" in the workspace.
I like to enter the same name for my Output Geometry into the "Model Name" field.
Enter a threshold value: 200 works well for bone, but for lower density bone, you might need to adjust it down. Since the Grayscale Model Maker is so fast, I usually start with 200 and make additional models at lower values to see which works best for the current volume.
***Here is where I adjust settings for pubic bones in order to retain the irregular surfaces of the symphyseal faces.***The default values for the Smoothing and Decimate parameters work well for other bones, but for the pubic symphyses, they tend to smooth out all the relevant features, so I slide them both all the way down.
Then hit Apply and wait for the model to appear in the 3D window (it will be gray).
You can see from the image above that my model is gray, but still has the beige from the Volume Render on it since I didn't close the Volume Rendering.
If for some reason you don't see your model: 1) check your Input Volume to make sure your subvolume is selected, 2) click on that tiny centering button at the top left of your 3D window, or 3) go to the main dropdown and go to "Models." If the model actually generated, it will be there with the name you specified, but sometimes the eye will be closed so just open it to look at your model.
Now we an save your subvolume and model using the Save button in the top left of the main toolbar. You can uncheck all the other options and just save the subvolume .nrrd and adjust the file type of your model to .stl. Click on "Change Directory" to specify where you want to save your files and Save!
This model still needs some editing to be printable, so stay tuned for Pt. 2 where I will discuss functions in Meshlab and Meshmixer.
Thanks for reading and please comment if you have any issues with these steps!
The utility of modern three-dimensional printing techniques for bio-medical and clinical use has been demonstrated repeatedly in recent years, with applications ranging from surgical modelling to tissue engineering and beyond.
Despite the promise and potential of three-dimensional printing methods, impediments to their widespread clinical uptake still remain. Many of the printers used for medical applications are highly specialised pieces of equipment that require trained operators and controlled operational conditions as well as potentially costly and unique raw materials. These factors can result in high production costs, and the necessity of dedicated sites which can in turn lead to delays between fabrication and clinical application.
Recent work by engineers and researchers at Zhejiang University in China has shown that desktop 3D-printing techniques may represent a more practical alternative for certain clinical tasks.
Desktop 3D printers may cost as little as $500, much less than the $15,000–30,000 machines routinely used in academic institutions. As well as the lower costs, Desktop 3D printers are considered to be much easier to operate. An Liu and co-workers tested the potential of these machines to fabricate bio-absorbable interference screws, used to secure hamstring tendon grafts commonly utilised to repair damaged anterior cruciate ligaments (ACL).
A screw-like scaffold, made from the same polylactic acid filament commonly used for conventional bio-absorbable screws, was printed using fused deposition modelling techniques then coated with hydroxyapatite (HA) to improve its osteoconductivity. The construct was also coated with mesenchymal stem cells, as these cells are widely considered to be of therapeutic value for anterior cruciate ligament regeneration.
A 3D porous structure is considered to be valuable to bone ingrowth into the screw, as this supports the cellular migration and mineral deposition, as well as vascular development, all required as the screw is incorporated into a patient’s bone. Conventional methods have struggled to control to formation of these structures, but by using 3D-printing techniques they can be easily manipulated by surgeons and specialists alike.
Once fabricated the 3D-printed screws were tested upon anterior cruciate ligament repairs in rabbits for up to three months. Magnetic resonance imaging showed that all of the 3D-printed screws were correctly positioned in the bone tunnel without any breakage or major complications, and that over the course of twelve weeks they appeared to incorporate into the bone tissue.
The approximate cost of a 3D printed bio-absorbable screw was 50 cents using industrial grade polylactic acid, and it is estimated that this equates to less than 10 USD using medical grade materials
The successful manufacture of a functional surgical device using desktop 3D printing technology demonstrates the potential for in situ fabrication at the clinic and opens up a range of in-house manufacturing possibilities to clinical staff, circumventing the requirement for costly equipment and bespoke materials as well as trained specialist operators.
3D Printing Surgical Implants at the clinic: A Experimental Study on Anterior Cruciate Ligament Reconstruction. Sci Rep. 2016 Feb 15;6:21704. doi: 10.1038/srep21704
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Getting from DICOM to 3D printable STL file in 3D Slicer is totally doable...but it is important to learn some fundamental skills in Slicer first if you are not familiar with the program.
This tutorial introduces the user to some basic concepts in 3D Slicer and demonstrates how to crop DICOM data in anticipation of segmentation and 3D model creation.
(Segmentation and STL file creation are explored in a companion tutorial )
This tutorial is downloadable as a PDF file,
or can be looked through in image/slide format here in the blog
My recent anatomy projects forced me to start importing my 3d models into 3d pdf documents. So I'll share with you some of my findings.
The positive things about 3d pdf's are:
1. You can import a big sized 3d model and compress it into a small 3d pdf. 40 Mb stl model is converted into 750 Kb pdf.
2. You can run the 3d pdf on every computer with the recent versions of Adobe Acrobat Reader. Which means literally EVERY computer.
3. You can rotate, pan, zoom in and zoom out 3d models in the 3d pdf. You can add some simple animations like spinning, sequence animations and explosion of multi component models.
4. You can add colors to the models and to create a 3d scene.
5. You can upload it on a website and it can be viewed in the browser (if Adobe Acrobat Reader is installed).
The negative things are:
1. Adobe Reader is a buggy 3d viewer. If you import a big model (bigger than 50 Mb) and your computer is business class (core I3 or I5, 4 Gb ram, integrated video card), you'll experience some nasty lag and the animation will look terrible. On the same computer regular 3d viewer will do the trick much better.
2. You can experience some difficulties with multi component models. During the rotation, some of the components will disappear, others will change their color. Also the model navigation toolbar is somewhat hard to control.
3. The transparent and wireframe polygon are not as good as in the regular 3d viewers.
If you want to demonstrate your models to a large audience, to sent it via email and to observe them on every computer, 3d pdf is your format. For a presentation it's better to use a regular 3d viewer, even the portable ones will do the trick. But if the performance is not the goal, 3d pdf's are a good alternative.
Here is a model of atlas and axis as 3d pfg: https://www.dropbox.com/s/2gm7occq5ur50um/vertebra.pdf?dl=0
So I have seen some questions here on embodi3D asking how to work with MRI data. I believe the main issue to be with attempting to segment the data using a threshold method. The democratiz3D feature of the website simplifies the segmentation process but as far as I can tell relies on thresholding which can work somewhat well for CT scans but for MRI is almost certain to fail. Using 3DSlicer I show the advantage of using a region growing method (FastGrowCut) vs threshold.
The scan I am using is of a middle aged woman's foot available here
The scan was optimized for segmenting bone and was performed on a 1.5T scanner. While a patient doesn't really have control of scan settings if you are a physician or researcher who does; picking the right settings is critical. Some of these different settings can be found on one of Dr. Mike's blog entries.
For comparison purposes I first showed the kind of results achievable when segmenting an MRI using thresholds.
With the goal of separating the bones out the result is obviously pretty worthless. To get the bones out of that resultant clump would take a ridiculous amount of effort in blender or similar software:
If you read a previous blog entry of mine on using a region growing method I really don't like using thresholding for segmenting anatomy. So once again using a region growing method (FastGrowCut in this case) allows decent results even from an MRI scan.
Now this was a relatively quick and rough segmentation of just the hindfoot but already it is much closer to having bones that could be printed. A further step of label map smoothing can further improve the rough results.
The above shows just the calcaneous volume smoothed with its associated surface generated. Now I had done a more proper segmentation of this foot in the past where I spent more time to get the below result
If the volume above is smoothed (in my case I used some of my matlab code) I can get the below result.
Which looks much better. Segmenting a CT scan will still give better results for bone as the cortical bone doesn't show up well in MRI's (why the metatarsals and phalanges get a bit skinny), but CT scans are not always an option.
So if you have been trying to segment an MRI scan and only get a messy clump I would encourage you to try a method a bit more modern than thresholding. However, keep in mind there are limits to what can be done with bad data. If the image is really noisy, has large voxels, or is optimized for the wrong type of anatomy there may be no way to get the results you want.
3D printing technologies have opened up the capabilities for customization in a wide variety of applications in the medical field. Using bio-compatible and drug-contact materials, medical devices can be produced that are perfectly suited for a particular individual. Another trend enabled by 3D printing is mass customization, in that multiple individualized items can be produced simultaneously, saving time and energy while improving manufacturing efficiency.
3D printers are used to manufacture a variety of medical devices, including those with complex geometry or features that match a patient’s unique anatomy.
Some devices are printed from a standard design to make multiple identical copies of the same device. Other devices, called patient-matched or patient-specific devices, are created from a specific patient’s imaging data.
Commercially available 3D printed medical devices include:
- Instrumentation (e.g., guides to assist with proper surgical placement of a device)
- Implants (e.g., cranial plates or hip joints)
- External prostheses (e.g., hands)
- Prescription Glasses
- Hearing Aids
In summary, the 3D Printing medical device market looks exciting and promising, Various Reports and surveys suggest the unexpected growth and demand for 3D Printing in medical device industry and it is expected to blossom more but a number of existing application areas for 3D printing in healthcare sector require specialized materials that meet rigid and stringent bio-compatibility standards, Future 3D printing applications for the medical device field will certainly emerge with the development of suitable additional materials for diagnostic and therapeutic use that meet CE and FDA guidelines.