Tag Archives: bio-ink

A 3D printed eye cornea and a 3D printed copy of your brain (also: a Brad Pitt connection)

Sometimes it’s hard to keep up with 3D tissue printing news. I have two news bits, one concerning eyes and another concerning brains.

3D printed human corneas

A May 29, 2018 news item on ScienceDaily trumpets the news,

The first human corneas have been 3D printed by scientists at Newcastle University, UK.

It means the technique could be used in the future to ensure an unlimited supply of corneas.

As the outermost layer of the human eye, the cornea has an important role in focusing vision.

Yet there is a significant shortage of corneas available to transplant, with 10 million people worldwide requiring surgery to prevent corneal blindness as a result of diseases such as trachoma, an infectious eye disorder.

In addition, almost 5 million people suffer total blindness due to corneal scarring caused by burns, lacerations, abrasion or disease.

The proof-of-concept research, published today [May 29, 2018] in Experimental Eye Research, reports how stem cells (human corneal stromal cells) from a healthy donor cornea were mixed together with alginate and collagen to create a solution that could be printed, a ‘bio-ink’.

Here are the proud researchers with their cornea,

Caption: Dr. Steve Swioklo and Professor Che Connon with a dyed cornea. Credit: Newcastle University, UK

A May 30,2018 Newcastle University press release (also on EurekAlert but published on May 29, 2018), which originated the news item, adds more details,

Using a simple low-cost 3D bio-printer, the bio-ink was successfully extruded in concentric circles to form the shape of a human cornea. It took less than 10 minutes to print.

The stem cells were then shown to culture – or grow.

Che Connon, Professor of Tissue Engineering at Newcastle University, who led the work, said: “Many teams across the world have been chasing the ideal bio-ink to make this process feasible.

“Our unique gel – a combination of alginate and collagen – keeps the stem cells alive whilst producing a material which is stiff enough to hold its shape but soft enough to be squeezed out the nozzle of a 3D printer.

“This builds upon our previous work in which we kept cells alive for weeks at room temperature within a similar hydrogel. Now we have a ready to use bio-ink containing stem cells allowing users to start printing tissues without having to worry about growing the cells separately.”

The scientists, including first author and PhD student Ms Abigail Isaacson from the Institute of Genetic Medicine, Newcastle University, also demonstrated that they could build a cornea to match a patient’s unique specifications.

The dimensions of the printed tissue were originally taken from an actual cornea. By scanning a patient’s eye, they could use the data to rapidly print a cornea which matched the size and shape.

Professor Connon added: “Our 3D printed corneas will now have to undergo further testing and it will be several years before we could be in the position where we are using them for transplants.

“However, what we have shown is that it is feasible to print corneas using coordinates taken from a patient eye and that this approach has potential to combat the world-wide shortage.”

Here’s a link to and a citation for the paper,

3D bioprinting of a corneal stroma equivalent by Abigail Isaacson, Stephen Swioklo, Che J. Connon. Experimental Eye Research Volume 173, August 2018, Pages 188–193 and 2018 May 14 pii: S0014-4835(18)30212-4. doi: 10.1016/j.exer.2018.05.010. [Epub ahead of print]

This paper is behind a paywall.

A 3D printed copy of your brain

I love the title for this May 30, 2018 Wyss Institute for Biologically Inspired Engineering news release: Creating piece of mind by Lindsay Brownell (also on EurekAlert),

What if you could hold a physical model of your own brain in your hands, accurate down to its every unique fold? That’s just a normal part of life for Steven Keating, Ph.D., who had a baseball-sized tumor removed from his brain at age 26 while he was a graduate student in the MIT Media Lab’s Mediated Matter group. Curious to see what his brain actually looked like before the tumor was removed, and with the goal of better understanding his diagnosis and treatment options, Keating collected his medical data and began 3D printing his MRI [magnetic resonance imaging] and CT [computed tomography] scans, but was frustrated that existing methods were prohibitively time-intensive, cumbersome, and failed to accurately reveal important features of interest. Keating reached out to some of his group’s collaborators, including members of the Wyss Institute at Harvard University, who were exploring a new method for 3D printing biological samples.

“It never occurred to us to use this approach for human anatomy until Steve came to us and said, ‘Guys, here’s my data, what can we do?” says Ahmed Hosny, who was a Research Fellow with at the Wyss Institute at the time and is now a machine learning engineer at the Dana-Farber Cancer Institute. The result of that impromptu collaboration – which grew to involve James Weaver, Ph.D., Senior Research Scientist at the Wyss Institute; Neri Oxman, [emphasis mine] Ph.D., Director of the MIT Media Lab’s Mediated Matter group and Associate Professor of Media Arts and Sciences; and a team of researchers and physicians at several other academic and medical centers in the US and Germany – is a new technique that allows images from MRI, CT, and other medical scans to be easily and quickly converted into physical models with unprecedented detail. The research is reported in 3D Printing and Additive Manufacturing.

“I nearly jumped out of my chair when I saw what this technology is able to do,” says Beth Ripley, M.D. Ph.D., an Assistant Professor of Radiology at the University of Washington and clinical radiologist at the Seattle VA, and co-author of the paper. “It creates exquisitely detailed 3D-printed medical models with a fraction of the manual labor currently required, making 3D printing more accessible to the medical field as a tool for research and diagnosis.”

Imaging technologies like MRI and CT scans produce high-resolution images as a series of “slices” that reveal the details of structures inside the human body, making them an invaluable resource for evaluating and diagnosing medical conditions. Most 3D printers build physical models in a layer-by-layer process, so feeding them layers of medical images to create a solid structure is an obvious synergy between the two technologies.

However, there is a problem: MRI and CT scans produce images with so much detail that the object(s) of interest need to be isolated from surrounding tissue and converted into surface meshes in order to be printed. This is achieved via either a very time-intensive process called “segmentation” where a radiologist manually traces the desired object on every single image slice (sometimes hundreds of images for a single sample), or an automatic “thresholding” process in which a computer program quickly converts areas that contain grayscale pixels into either solid black or solid white pixels, based on a shade of gray that is chosen to be the threshold between black and white. However, medical imaging data sets often contain objects that are irregularly shaped and lack clear, well-defined borders; as a result, auto-thresholding (or even manual segmentation) often over- or under-exaggerates the size of a feature of interest and washes out critical detail.

The new method described by the paper’s authors gives medical professionals the best of both worlds, offering a fast and highly accurate method for converting complex images into a format that can be easily 3D printed. The key lies in printing with dithered bitmaps, a digital file format in which each pixel of a grayscale image is converted into a series of black and white pixels, and the density of the black pixels is what defines the different shades of gray rather than the pixels themselves varying in color.

Similar to the way images in black-and-white newsprint use varying sizes of black ink dots to convey shading, the more black pixels that are present in a given area, the darker it appears. By simplifying all pixels from various shades of gray into a mixture of black or white pixels, dithered bitmaps allow a 3D printer to print complex medical images using two different materials that preserve all the subtle variations of the original data with much greater accuracy and speed.

The team of researchers used bitmap-based 3D printing to create models of Keating’s brain and tumor that faithfully preserved all of the gradations of detail present in the raw MRI data down to a resolution that is on par with what the human eye can distinguish from about 9-10 inches away. Using this same approach, they were also able to print a variable stiffness model of a human heart valve using different materials for the valve tissue versus the mineral plaques that had formed within the valve, resulting in a model that exhibited mechanical property gradients and provided new insights into the actual effects of the plaques on valve function.

“Our approach not only allows for high levels of detail to be preserved and printed into medical models, but it also saves a tremendous amount of time and money,” says Weaver, who is the corresponding author of the paper. “Manually segmenting a CT scan of a healthy human foot, with all its internal bone structure, bone marrow, tendons, muscles, soft tissue, and skin, for example, can take more than 30 hours, even by a trained professional – we were able to do it in less than an hour.”

The researchers hope that their method will help make 3D printing a more viable tool for routine exams and diagnoses, patient education, and understanding the human body. “Right now, it’s just too expensive for hospitals to employ a team of specialists to go in and hand-segment image data sets for 3D printing, except in extremely high-risk or high-profile cases. We’re hoping to change that,” says Hosny.

In order for that to happen, some entrenched elements of the medical field need to change as well. Most patients’ data are compressed to save space on hospital servers, so it’s often difficult to get the raw MRI or CT scan files needed for high-resolution 3D printing. Additionally, the team’s research was facilitated through a joint collaboration with leading 3D printer manufacturer Stratasys, which allowed access to their 3D printer’s intrinsic bitmap printing capabilities. New software packages also still need to be developed to better leverage these capabilities and make them more accessible to medical professionals.

Despite these hurdles, the researchers are confident that their achievements present a significant value to the medical community. “I imagine that sometime within the next 5 years, the day could come when any patient that goes into a doctor’s office for a routine or non-routine CT or MRI scan will be able to get a 3D-printed model of their patient-specific data within a few days,” says Weaver.

Keating, who has become a passionate advocate of efforts to enable patients to access their own medical data, still 3D prints his MRI scans to see how his skull is healing post-surgery and check on his brain to make sure his tumor isn’t coming back. “The ability to understand what’s happening inside of you, to actually hold it in your hands and see the effects of treatment, is incredibly empowering,” he says.

“Curiosity is one of the biggest drivers of innovation and change for the greater good, especially when it involves exploring questions across disciplines and institutions. The Wyss Institute is proud to be a space where this kind of cross-field innovation can flourish,” says Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School (HMS) and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at Harvard’s John A. Paulson School of Engineering and Applied Sciences (SEAS).

Here’s an image illustrating the work,

Caption: This 3D-printed model of Steven Keating’s skull and brain clearly shows his brain tumor and other fine details thanks to the new data processing method pioneered by the study’s authors. Credit: Wyss Institute at Harvard University

Here’s a link to and a citation for the paper,

From Improved Diagnostics to Presurgical Planning: High-Resolution Functionally Graded Multimaterial 3D Printing of Biomedical Tomographic Data Sets by Ahmed Hosny , Steven J. Keating, Joshua D. Dilley, Beth Ripley, Tatiana Kelil, Steve Pieper, Dominik Kolb, Christoph Bader, Anne-Marie Pobloth, Molly Griffin, Reza Nezafat, Georg Duda, Ennio A. Chiocca, James R.. Stone, James S. Michaelson, Mason N. Dean, Neri Oxman, and James C. Weaver. 3D Printing and Additive Manufacturing http://doi.org/10.1089/3dp.2017.0140 Online Ahead of Print:May 29, 2018

This paper appears to be open access.

A tangential Brad Pitt connection

It’s a bit of Hollywood gossip. There was some speculation in April 2018 that Brad Pitt was dating Dr. Neri Oxman highlighted in the Wyss Institute news release. Here’s a sample of an April 13, 2018 posting on Laineygossip (Note: A link has been removed),

It took him a long time to date, but he is now,” the insider tells PEOPLE. “He likes women who challenge him in every way, especially in the intellect department. Brad has seen how happy and different Amal has made his friend (George Clooney). It has given him something to think about.”

While a Pitt source has maintained he and Oxman are “just friends,” they’ve met up a few times since the fall and the insider notes Pitt has been flying frequently to the East Coast. He dropped by one of Oxman’s classes last fall and was spotted at MIT again a few weeks ago.

Pitt and Oxman got to know each other through an architecture project at MIT, where she works as a professor of media arts and sciences at the school’s Media Lab. Pitt has always been interested in architecture and founded the Make It Right Foundation, which builds affordable and environmentally friendly homes in New Orleans for people in need.

“One of the things Brad has said all along is that he wants to do more architecture and design work,” another source says. “He loves this, has found the furniture design and New Orleans developing work fulfilling, and knows he has a talent for it.”

It’s only been a week since Page Six first broke the news that Brad and Dr Oxman have been spending time together.

I’m fascinated by Oxman’s (and her colleagues’) furniture. Rose Brook writes about one particular Oxman piece in her March 27, 2014 posting for TCT magazine (Note: Links have been removed),

MIT Professor and 3D printing forerunner Neri Oxman has unveiled her striking acoustic chaise longue, which was made using Stratasys 3D printing technology.

Oxman collaborated with Professor W Craig Carter and Composer and fellow MIT Professor Tod Machover to explore material properties and their spatial arrangement to form the acoustic piece.

Christened Gemini, the two-part chaise was produced using a Stratasys Objet500 Connex3 multi-colour, multi-material 3D printer as well as traditional furniture-making techniques and it will be on display at the Vocal Vibrations exhibition at Le Laboratoire in Paris from March 28th 2014.

An Architect, Designer and Professor of Media, Arts and Science at MIT, Oxman’s creation aims to convey the relationship of twins in the womb through material properties and their arrangement. It was made using both subtractive and additive manufacturing and is part of Oxman’s ongoing exploration of what Stratasys’ ground-breaking multi-colour, multi-material 3D printer can do.

Brook goes on to explain how the chaise was made and the inspiration that led to it. Finally, it’s interesting to note that Oxman was working with Stratasys in 2014 and that this 2018 brain project is being developed in a joint collaboration with Statasys.

That’s it for 3D printing today.

A cheaper way to make artificial organs

In the quest to develop artificial organs, the University of British Columbia (UBC) is the not the first research institution that comes to my mind. It seems I may need to reevaluate now that UBC (Okanagan) has announced some work on bio-inks and artificial organs in a Sept. 12, 2017 news  release (also on EurekAlert) by Patty Wellborn,,

A new bio-ink that may support a more efficient and inexpensive fabrication of human tissues and organs has been created by researchers at UBC’s Okanagan campus.

Keekyoung Kim, an assistant professor at UBC Okanagan’s School of Engineering, says this development can accelerate advances in regenerative medicine.

Using techniques like 3D printing, scientists are creating bio-material products that function alongside living cells. These products are made using a number of biomaterials including gelatin methacrylate (GelMA), a hydrogel that can serve as a building block in bio-printing. This type of bio-material—called bio-ink—are made of living cells, but can be printed and molded into specific organ or tissue shapes.

The UBC team analyzed the physical and biological properties of three different GelMA hydrogels—porcine skin, cold-water fish skin and cold-soluble gelatin. They found that hydrogel made from cold-soluble gelatin (gelatin which dissolves without heat) was by far the best performer and a strong candidate for future 3D organ printing.

“A big drawback of conventional hydrogel is its thermal instability. Even small changes in temperature cause significant changes in its viscosity or thickness,” says Kim. “This makes it problematic for many room temperature bio-fabrication systems, which are compatible with only a narrow range of hydrogel viscosities and which must generate products that are as uniform as possible if they are to function properly.”

Kim’s team created two new hydrogels—one from fish skin, and one from cold-soluble gelatin—and compared their properties to those of porcine skin GelMA. Although fish skin GelMA had some benefits, cold-soluble GelMA was the top overall performer. Not only could it form healthy tissue scaffolds, allowing cells to successfully grow and adhere to it, but it was also thermally stable at room temperature.

The UBC team also demonstrated that cold-soluble GelMA produces consistently uniform droplets at temperatures, thus making it an excellent choice for use in 3D bio-printing.

“We hope this new bio-ink will help researchers create improved artificial organs and lead to the development of better drugs, tissue engineering and regenerative therapies,” Kim says. “The next step is to investigate whether or not cold-soluble GelMA-based tissue scaffolds are can be used long-term both in the laboratory and in real-world transplants.”

Three times cheaper than porcine skin gelatin, cold-soluble gelatin is used primarily in culinary applications.

Here’s a link to and a citation for the paper,

Comparative study of gelatin methacrylate hydrogels from different sources for biofabrication applications by Zongjie Wang, Zhenlin Tian, Fredric Menard, and Keekyoung Kim. Biofabrication, Volume 9, Number 4 Special issue on Bioinks https://doi.org/10.1088/1758-5090/aa83cf Published 21 August 2017

© 2017 IOP Publishing Ltd

This paper is behind a paywall.

A new bio-ink, inkjet printers, and printing human cells at Australia’s University of Wollongong

Sometimes I look at my printer and just shake my head at the thought that one day it might produce living cells if the researchers at University of  Wollongong (New South Wales, Australia) have their way. From the Nov. 16, 2012 news item on phys.org,

Researchers have been aware for some time of the potential for using commercially available inkjet printer heads to print living human cells into 3D structures, but design of the actual ink capable of carrying cells through the printer has been a challenge.

The ARC Centre of Excellence for Electromaterials Science at UOW has led a team of scientists including Cameron Ferris, Dr Kerry Gilmore, Dr Stephen Beirne, Dr Donald McCallum, Professor Gordon Wallace and Associate Professor Marc in het Panhuis to develop a new bio-ink that improves the viability of living cells and allows better control of cell positioning through the printing process.

“To date, none of the available inks has been optimised in terms of both printability and cell suspending ability,” according to ACES Associate Researcher Cameron Ferris.

“Our new bio-ink is printable and cell-friendly, preventing cell settling and allowing controlled deposition of cells.”

The Nov. 15, 2012 University of Wollogong news release, which originated the news item, provides some detail about what makes this new bio-ink exciting,

The 2D structures being printed with the bio-ink enables exquisite control over cell distribution and this already presents exciting opportunities to improve drug screening and toxicology testing processes. Building on this, 3D bio-printing, with which patient-specific tissue replacements could be fabricated, is within the grasp of researchers.

The abstract for the researchers’ paper in Biomaterials helped me to build my understanding of this innovation,

Drop-on-demand bioprinting allows the controlled placement of living cells, and will benefit research in the fields of tissue engineering, drug screening and toxicology. We show that a bio-ink based on a novel microgel suspension in a surfactant-containing tissue culture medium can be used to reproducibly print several different cell types, from two different commercially available drop-on-demand printing systems, over long printing periods. The bio-ink maintains a stable cell suspension, preventing the settling and aggregation of cells that usually impedes cell printing, whilst meeting the stringent fluid property requirements needed to enable printing even from many-nozzle commercial inkjet print heads. This innovation in printing technology may pave the way for the biofabrication of multi-cellular structures and functional tissue.

You can access the paper (free access) but you must be registered (it’s free) with RSC (Royal Society of Chemistry) Publishing. Here’s a link and the citation,

Bio-ink for on-demand printing of living cells

Cameron J. Ferris ,  Kerry J. Gilmore ,  Stephen Beirne ,  Donald McCallum ,  Gordon G. Wallace and Marc in het Panhuis

Biomater. Sci., 2013, Advance Article

DOI: 10.1039/C2BM00114D
Received 09 Aug 2012, Accepted 11 Oct 2012
First published on the web 05 Nov 2012

Even more helpful than the abstract and assuming you’re not ready to read the paper is Jennifer Newton’s Nov. 7, 2012 article for the RSC’s Chemistry World,

‘The first bio-inks used in drop-on-demand cell printing were simple salt solutions,’ says Marc in het Panhuis, who was part of the research team at the University of Wollongong. ‘The cells in these inks settled and aggregated quickly, which impeded printing. Cell viability can also be compromised if the salt concentration is too high.’

Other bio-inks include low viscosity biopolymer solutions, which are known to slow cell settling. The team’s bio-ink consists of a biopolymer – gellan gum – and two surfactants in a standard tissue culture medium. The surfactants – Novec FC4430 and Poloxamer 188 – reduce surface tension, allowing optimal inkjet printing, and protect the cells from fluid-mechanical damage.

The cells do not settle and aggregate because the biopolymer creates a structured network of micro-gel particles that keep the cells suspended in the gel. However, the bio-ink remains printable as the network is not rigid and is easily broken down during printing. ‘Our bio-ink allowed us to print multiple cell types over long printing periods without changing print heads or replenishing ink solutions,’ says in het Panhuis.

There are more details in Newton’s article and the image that accompanies it is quite striking.