Scientists at the University of Glasgow have successfully implemented an innovative new treatment for creating synthetic bones into a dog. The process is hoped to lead to human bone implants from a 3D printer.

The implantation was used to save the two-years old Munsterlander named Eva and the technology was funded by the Find a Better Way charity. Founded by Sir Bobby Charlton, Find a Better Way announced a £2.8m financial agreement with the University of Glasgow last year. The partnership was made with the aim of developing 3D printed limbs.

Giving the dog a bone

Eva’s front leg was broken during a car accident and since hasn’t been able to heal due to persistent infections requiring bone tissue to be removed. As a result, Eva was left with a 2 cm gap in her foreleg bone and was close to amputation. However, vet William Marshall discovered a possible treatment in the form of an untested technique developed at the University of Glasgow.

Using a protein known as BMP-2, the scientists were able to encourage bone growth but were not yet due to trial the method on humans for another few years.

William Marshall took the gamble and implanted a combination of BMP-2, a binding agent known as poly(ethyl acrylate) or PEA and bone chips and Eva’s bone marrow. As it was the first use of the technique, the results were unprecedented and seven weeks later Eva has made a full recovery.

Paving the way for synthetic 3D printed bones

Having demonstrated the potential with Eva’s implantation, the team at the University of Glasgow will use the procedure as a learning exercise for future 3D printed implantations.

The same BMP-2 process will be used in the future with 3D printed scaffolds and stem cells to treat landmine survivors in Cambodia. The technique works by using biomedical grade plastic which eventually dissolves to leave a newly-grown bone in its place. The 3D printing technology has potential not just for land mine victims but for promoting bone growth across the body. Sir Bobby Charlton describes the significance of the surprising development,

When I signed the funding agreement for this project just six months ago I was not expecting there to be any results from this technology for years. Eva is a beautiful dog and I’m delighted she will now have a normal life thanks to the work Find A Better Way has funded at the University of Glasgow. I’m even more thrilled to think about what promise this technique holds for landmine blast survivors, and the rest of humanity, in the future.

Californian company SI-BONE is similarly using 3D printing to promote bone growth with titanium implants. The company has just been granted FDA clearance.

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Tyler Koslow from 3D Printing Industry

Coming out of Sweden, the startup CELLINK has been working to revolutionize the 3D bioprinting market, releasing their unbelievably low-priced INKREDIBLE desktop bioprinter last year for just $5,000. Since then, CELLINK has been developing new cellular inks, a network for downloadable 3D biomodels, and now, according to the 3DP Business Directory, they have released two brand new bioinks. The two newly developed biomaterials are geared to improve our ability to bioprint with human tissue and organs, further bringing this increasingly capable 3D technology out of well-funded research labs and into a market that is much more accessible to all researchers, scientists, and students.

The first newly released ink, CELLINK A, is composed of ultra-pure alginate, a biomaterial that has reportedly been in demand from CELLINK customers for some time. The biodegradable bioink is best suited for situations where the scaffolding material must be replaced by native tissue. Alginate gels have long been used by scientist and medical companies for cell encapsulation and 3D cell culturing, but this traditional method generally leads to less control over the architecture of the scaffold. But with CELLINK’s desktop bioprinter and alginate-based bioink, scientists and researchers can now better study the use of alginate biomaterial for tissue regeneration. Other alginate-based products have been okayed for implementation in humans, and the new bioink could soon help move experimentation from in vitro (performed on microorganisms, cells, etc) to actual clinical application.

“CELLINK A is conveniently crosslinked using the same binding agent that is offered with the original CELLINK bioink to make things as simple as possible for the end-users,” said Ida Henriksson, CBO of CELLINK. “We want to ensure that our customers concentrate their valuable time on what they do best: 3D cell culturing. Therefore is it important that our bioinks provide the highest level of reproducibility, quality, and ease of use.”

The other newly developed CELLINK bioink is called SUPPORTINK, which was specifically engineered to help with “co-printing” complex 3D structures that require sacrificial structures. SUPPORTINK can be easily removed from the structure once the cells are printed and stabilized, only needing a simple rinsing, which allows for the creation of tissue models that are equipped with open vascular-resembling networks that can be used for a number of applications, such as perfusion with oxygen and culture media.
As they continue building upon their well-established desktop bioprinting technology, CELLINK is helping to bring bioengineering straight onto the desk in a compact and low-cost way. The rise of affordable desktop bioprinting is allowing for more access, and thus, more research with this emerging technology. The Swedish startup is becoming one of the trailblazers for 3D bioprinting, and these new bioinks will hopefully help scientists and researchers improve the way human tissues and organs are ‘3D printed’.

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Tyler Koslow from 3D Printing Industry

It’s no secret that 3D printing is a terrific tool for the production of prosthetics, but one non-profit organization from Central Florida, named Limbitless Solutions, is taking 3D printed prosthetics to the next level by creating personalized bionics. Limbitless Solutions, I’m proud to say, is a student group based out of my alma mater, the University of Central Florida. They’ve helped kids become superheroes with their 3D printed bionic arms, and have even found their work on the 2016 New York Fashion Week runway. Now, the non-profit group has created a 3D printed bionic arm for ten-year-old Julianna Linton, an avid cheerleader who had lost her left arm above the elbow because of a congenital amputation caused by the unfortunate amniotic band syndrome.

Julianna is now the 15th child to receive a 3D printed bionic arm from Limbitless Solutions, who provides these personalized prosthetics to the children at no cost. The group was founded by aerospace engineering student Albert Manero, who is currently pursuing his PhD at UCF. The 3D printed bionic arm is designed with the UCF logo and colors in tact, making it more than just a bionic prosthetic, but also a part of her cheerleader uniform.
After Julianna practiced with her bionic arm for the first time, she had a cheer clinic put on for her at the Bright House Networks Stadium. Julianna was also given a tour of the UCF campus with the university’s cheerleading squad, led by coach Linda Gooch. Upon receiving the arm, Julianna proceeded to perform 20 cartwheels in front of a cheerful, supportive crowd. Her parents, Clark and Kathleen Linton, seem to think that this is just the beginning of a improved life for their daughter.

“If there are 10,000 things someone with two arms can do, Julianna can already do 9,900,” said Clark Linton. “We’ve always focused on what she can do, not what she can’t. I think this new arm will give her the opportunity to do even more. The technology is advancing so rapidly, Julianna has a chance to grow with the technology that may help her later on in life and won’t limit her career opportunities.”

Limbitless Solutions is pushing the message that Julianna, and other girls and boys with similar disabilities, truly have no limit to what they can accomplish. Their 3D printed bionic arm prosthetics have not only provided a handful of children with an adequate assistive device, but have made them the center of attention in the most positive way possible.

“We want children to know, especially girls, that there are no limits,” said Manero. “We want them to dream big and then go after it. That’s really important. You can be smart, beautiful and strong and do it all here at UCF.” I’ll admit I haven’t felt much school spirit since graduating back from UCF back in 2012, but Limbitless Solutions certainly makes me feel proud to be a Knight!

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While we’ve previously seen how 3D printing has been life-changing for young superheroes in need of a prosthetic arm – or even our four-legged friends for that matter – we’ve been yet to hear very many stories about the technology is helping to aid the deaf and blind in living a fuller life … until now.

Many of us might not be able to imagine being blind or deaf, but for the recently-widowed Faith Altheide, being both blind and deaf is an everyday reality.  Among other ways that Faith communicates and expresses emotions with others is in feeling their facial features.  With her daughter Denise heading off to college this fall, this means that Faith will no longer be able to experience her daughter’s presence like she’s been used to for the past 18 years – through touch.

Aiming to help make this transition easier for Faith, Faith’s caregiver Patricia Ingraham reached out to Maconaquah Middle School in Bunker Hill, Indiana to see if they would be able to create a 3D printed replica of Denise.  Without hesitation, Maconaquah teachers Ron Shaffer and Cory Howard agreed to take on the project.   

To create the 3D printed replica of Denise, Shaffer and Howard began the process by taking a series of photographs of Denise that were then stitched together to create a 3D model – a process that has been made easier now thanks to an ever-increasing range of software options.  

Once the 3D model was made, Shaffer and Howard cleaned it up so that it would be optimized for the 3D printing process.  At this stage, they also adjusted the 3D print settings using MakerBot’s MakerWare so that the model would be both light and durable enough to be used regularly.  Finally, the optimized 3D model was then printed on a MakerBot Replicator using white PLA filament.  

While we’ve seen 3D printed busts such as the one created by Shaffer and Howard before – particularly those that have been created using 3D scanning booths – it’s clear that this is among one of the best uses for both 3D scanning and 3D printing technologies when it’s put to great use.  

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Organovo is steadily on track with its organ bioprinting research. Having conducted a number of studies, the company has already released its first cellular assay of liver tissue, exVive3D, for pharmaceutical testing purposes. Now, the bioprinting firm is moving onto human kidney tissue. At the 2015 Experimental Biology conference in Boston, today, Organovo gave attendees a look at the work done so far on their in vitro three-dimensional kidney tissue.

At the conference, Organovo presented their latest research, 3D printed a part of the duct system attached to the kidney, “kidney proximal tubular tissues“, using multiple cell types. Moreover, the tissue was able to survive in vitro for two weeks. This specific portion of the kidney may aid in the testing of medicines and the fact that they are made up of three different cell types will contribute to that application further, as well as provide a stepping stone to even more complex tissues.

Credit: Organovo. “Organovo has described the first 3D bioprinted human kidney tissue, which is a significant advance over simple single layer cell cultures that are used today for drug testing and disease research. This image shows that the tissue is composed of different types of kidney cells that make up the proximal tubule, which plays a pivotal role in kidney disease. The tissue is 100% cellular (no scaffolds) with clear cellular connections and tissue architecture. (Not shown) The tissue also expresses normal kidney enzymes such as CYP450 (enzymes responsible for breaking down drugs) and gamma glutamyl transferase (GGT) activity, both of which are indicators of specific kidney cell (RPTEC) function. Key to colors and marks Tissues were stained with antibodies against two of the three different cell types found in the tissue: endothelial cell specific marker CD31 (green) and fibroblast marker TE7 (red). The third cell type is the polarized renal proximal tubular epithelial cells (RPTEC). The endothelial cells will associate with each other, forming networks. Over time, the center of these networks will “hollow out” to form microvessel lumens lined with epithelial cells. Networks with putative lumens lined with endothelial cells are marked (*).”

Organovo CTO and Executive Vice President of Research and Development, Dr. Sharon Presnell, explains, “Our bioprinted human kidney tissue represents a significant technical advance over the simple monolayer cell line cultures that predominate today. The histologic and functional features of the initial prototypes are compelling, and the in vitro durability of the system will likely enable the assessment of drug effects at chronic, physiologically relevant doses. Furthermore, the cellular complexity of the system will likely support mechanistic investigations into drug responses, including end points that have been difficult or impossible to assess in vitro, including tubular fibrosis and post-injury recovery.”

Kidney disease affects more than 25 million people in the United States and these printed tissues are a first step towards treating such diseases as polycystic kidney disease and, one day in the future, creating printed kidneys for transplant. Though that day is likely a long way off, printed organs would bypass the need for immunosuppressants that both prevent the body from rejecting alien organs and cause many post-transplant complications. Because that day is a long way off, however, organ donation is still vital to the survival of the more than 123,000 people on organ waiting lists in the US. This also means that the kidney tissue from Organovo will be used for pharmaceutical testing in the short term.

The company’s CEO, Keith Murphy, elaborates, “Kidney represents an ideal extension of Organovo’s capabilities to 3D bioprint organ tissues that can be tremendously useful in pharmaceutical research. The results released today admirably demonstrate a proof of concept that kidney is on the way to becoming another core commercial tissue for Organovo. The product that we intend to build from these initial results can be an excellent expansion for our core customers in toxicology, who regularly express to us an interest in having better solutions for the assessment of human kidney toxicity.”

Organovo states: “Nearly one in five drug candidates fail Phase 3 clinical trials because of kidney toxicity. Only a handful of poor models are used today to test a drug’s impact on the kidneys.” If the company can produce a new product, similar to that of their exVive3D liver assay, for the kidney, researchers may have a more viable method for testing drug toxicity on the kidneys, ensuring that medicines can get to market more quickly, with less of a chance of them being later removed from shelves, due to inadequate tools for proper research.

The tissue construct consists of three types of human cells: epithelial cells (RPTEC), a living interstitial layer made from renal fibroblasts (RF), and endothelial cells (EC), all of which have maintained their proper shape and survived for two weeks in vitro. Not only that, but microvascular structures grew in the tissue during this time. Or, as the company puts it:

The kidney proximal tubule tissue is multi-cellular and fully human, consisting of polarized renal proximal tubular epithelial cells (RPTEC) and a living interstitial layer comprised of renal fibroblasts (RF), and endothelial cells (EC). Immunohistochemical analysis shows clear evidence of intercellular junction formation (E-Cadherin+) between the epithelial cells, extensive formation of microvascular structures, and stable maintenance of the layered architecture for at least two weeks in vitro. The epithelial cells within the multi-layered tubular model express CYP450 mRNAs and possess gamma glutamyl transferase (GGT) activity, both of which are indicators of RPTEC function. Importantly, our initial characterization shows that the expression of GGT increases over two weeks post-fabrication, indicating a gain-of-function over time.

Image via onlinehumananatomycourse.net

Speaking with Loyola University Medical Center’s Dr. Susan Hou, a well-regarded nephrologist who is also my mom, I was able to gain a better understanding of what this specific portion of the kidney is: “The kidney is made up of filtering units called glomerulae; they’re collections of capillaries that filter the blood, the function of the kidney. They filtered probably 100x what you need to get rid of. And there are tubules made up of four parts: the proximal, the loop of Henle, distal, and the collecting duct. These take back all of the waste that you don’t need to get rid of. So, it’s great to make proximal tubular cells, but, without the glomerulus, you can’t have any function of the kidney.”

She wasn’t able to comment specifically on the exhibited function of the epithelial cells demonstrated by Organovo’s research, as I was reading the company’s press release to her over the phone and probably mispronouncing “gamma glutamyl transferase”, but she did underscore the importance of the fact that they were able to print the “living interstitial layer comprised of renal fibroblasts (RF), and endothelial cells (EC)”, saying, “They’re a little bit closer to making the whole kidney if they’ve got the proximal tubule in the right position with the part of the kidney that’s between the filtering units.” In other words, Organovo is making significant progress, but still has some ways to go before 3D printing an entire, functioning kidney.

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Andrew Wheeler from 3D Printing Industry

A new 3D printed anatomy kit for medical students is now available to ship worldwide. This is certainly one of the more practical and useful ways to use 3D printing.
Melbourne, Australia-based scientists at Monash University developed the kit, which is the first resource of its kind to be commercially available. The team announced this project last year and have been working on it ever since using laser hand-held scanners, CT scans and MRI imaging.

Paul McMenamin, Director of the University’s Centre for Human Anatomy Education explains, “For centuries cadavers bequested to medical schools have been used to teach students about human anatomy, a practice that continues today. However many medical schools report either a shortage of cadavers, or find their handling and storage too expensive as a result of strict regulations governing where cadavers can be dissected.”
The kit contains no human tissue, but rather representative high resolution, color 3D models of limbs, chest, abdomen, head and neck printed using plastic or a plaster like powder. Instead of medical students having to deal with getting on the long waiting list for preserved cadavers or plastinated bodies that cost hundreds of thousands of dollars, they can have anatomically correct models of human body parts within weeks at a fraction of the cost. Some of the models can actually show areas of the body that are impossible to visualize in an embalmed cadaver like the intricate vasculature of the brain with its fine, spidery arteries and veins nestled against the human skull.

McMenamin continues, “we believe our kit will revolutionize learning for medical students by enabling them to look inside the body and see the muscles, tendons, ligaments, and blood vessels. At the moment it can be incredibly hard for students to understand the three-dimensional form of the human anatomy, and we believe this kit will make a huge difference – a sort of 3D textbook if you like.”
Hopefully the kind of 3D textbook so crucial in the training of doctors will branch out to include 3D learning in other fields. McMenamin wholeheartedly believes that the knowledge gleaned from his team’s anatomy kit will not only better medical professionals but also patients as well.

German anatomical model makers, Erler-Zimmer have made the kit available on their online store. We are excited about such a brilliant use of 3D technology and the future of 3D learning.

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