3D-printed blood vessels bring artificial organs closer to reality

Growing functional human organs outside the body is a long-sought "holy grail" of organ transplantation medicine that remains elusive. New research from Harvard's Wyss Institute for Biologically Inspired Engineering and John A. Paulson School of Engineering and Applied Science (SEAS) brings that quest one big step closer to completion.

A team of scientists created a new method to 3D print vascular networks that consist of interconnected blood vessels possessing a distinct "shell" of smooth muscle cells and endothelial cells surrounding a hollow "core" through which fluid can flow, embedded inside a human cardiac tissue. This vascular architecture closely mimics that of naturally occurring blood vessels and represents significant progress toward being able to manufacture implantable human organs. The achievement is published in Advanced Materials.

"In prior work, we developed a new 3D bioprinting method, known as "sacrificial writing in functional tissue" (SWIFT), for patterning hollow channels within a living cellular matrix. Here, building on this method, we introduce coaxial SWIFT (co-SWIFT) that recapitulates the multilayer architecture found in native blood vessels, making it easier to form an interconnected endothelium and more robust to withstand the internal pressure of blood flow," said first author Paul Stankey, a graduate student at SEAS in the lab of co-senior author and Wyss Core Faculty member Jennifer Lewis, Sc.D.

The key innovation developed by the team was a unique core-shell nozzle with two independently controllable fluid channels for the "inks" that make up the printed vessels: a collagen-based shell ink and a gelatin-based core ink. The interior core chamber of the nozzle extends slightly beyond the shell chamber so that the nozzle can fully puncture a previously printed vessel to create interconnected branching networks for sufficient oxygenation of human tissues and organs via perfusion. The size of the vessels can be varied during printing by changing either the printing speed or the ink flow rates.

To confirm the new co-SWIFT method worked, the team first printed their multilayer vessels into a transparent granular hydrogel matrix. Next, they printed vessels into a recently created matrix called uPOROS composed of a porous collagen-based material that replicates the dense, fibrous structure of living muscle tissue. They were able to successfully print branching vascular networks in both of these cell-free matrices. After these biomimetic vessels were printed, the matrix was heated, which caused collagen in the matrix and shell ink to crosslink, and the sacrificial gelatin core ink to melt, enabling its easy removal and resulting in an open, perfusable vasculature.

Moving into even more biologically relevant materials, the team repeated the printing process using a shell ink that was infused with smooth muscle cells (SMCs), which comprise the outer layer of human blood vessels. After melting out the gelatin core ink, they then perfused endothelial cells (ECs), which form the inner layer of human blood vessels, into their vasculature. After seven days of perfusion, both the SMCs and the ECs were alive and functioning as vessel walls -- there was a three-fold decrease in the permeability of the vessels compared to those without ECs.

Finally, they were ready to test their method inside living human tissue. They constructed hundreds of thousands of cardiac organ building blocks (OBBs) -- tiny spheres of beating human heart cells, which are compressed into a dense cellular matrix. Next, using co-SWIFT, they printed a biomimetic vessel network into the cardiac tissue. Finally, they removed the sacrificial core ink and seeded the inner surface of their SMC-laden vessels with ECs via perfusion and evaluated their performance.

Not only did these printed biomimetic vessels display the characteristic double-layer structure of human blood vessels, but after five days of perfusion with a blood-mimicking fluid, the cardiac OBBs started to beat synchronously -- indicative of healthy and functional heart tissue. The tissues also responded to common cardiac drugs -- isoproterenol caused them to beat faster, and blebbistatin stopped them from beating. The team even 3D-printed a model of the branching vasculature of a real patient's left coronary artery into OBBs, demonstrating its potential for personalized medicine.

"We were able to successfully 3D-print a model of the vasculature of the left coronary artery based on data from a real patient, which demonstrates the potential utility of co-SWIFT for creating patient-specific, vascularized human organs," said Lewis, who is also the Hansjörg Wyss Professor of Biologically Inspired Engineering at SEAS.

In future work, Lewis' team plans to generate self-assembled networks of capillaries and integrate them with their 3D-printed blood vessel networks to more fully replicate the structure of human blood vessels on the microscale and enhance the function of lab-grown tissues.

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Custom implants on demand? Bandages for the heart? 3D printing method makes it possible

In the quest to develop life-like materials to replace and repair human body parts, scientists face a formidable challenge: Real tissues are often both strong and stretchable and vary in shape and size.

A CU Boulder-led team, in collaboration with researchers at the University of Pennsylvania, has taken a critical step toward cracking that code. They've developed a new way to 3D print material that is at once elastic enough to withstand a heart's persistent beating, tough enough to endure the crushing load placed on joints, and easily shapable to fit a patient's unique defects.

Better yet, it sticks easily to wet tissue.

Their breakthrough, described in the Aug. 2 edition of the journal Science, helps pave the way toward a new generation of biomaterials, from internal bandages that deliver drugs directly to the heart to cartilage patches and needle-free sutures.

"Cardiac and cartilage tissues are similar in that they have very limited capacity to repair themselves. When they're damaged, there is no turning back," said senior author Jason Burdick, a professor of chemical and biological engineering at CU Boulder's BioFrontiers Institute. "By developing new, more resilient materials to enhance that repair process, we can have a big impact on patients."

Worm 'blobs' as inspiration

Historically, biomedical devices have been created via molding or casting, techniques which work well for mass production of identical implants but aren't practical when it comes to personalizing those implants for specific patients. In recent years, 3D printing has opened a world of new possibilities for medical applications by allowing researchers to make materials in many shapes and structures.

Unlike typical printers, which simply place ink on paper, 3D printers deposit layer after layer of plastics, metals or even living cells to create multidimensional objects.

One specific material, known as a hydrogel (the stuff that contact lenses are made of), has been a favorite prospect for fabricating artificial tissues, organs and implants.

But getting these from the lab to the clinic has been tough because traditional 3D-printed hydrogels tend to either break when stretched, crack under pressure or are too stiff to mold around tissues.

"Imagine if you had a rigid plastic adhered to your heart. It wouldn't deform as your heart beats," said Burdick. "It would just fracture."

To achieve both strength and elasticity within 3D printed hydrogels, Burdick and his colleagues took a cue from worms, which repeatedly tangle and untangle themselves around one another in three-dimensional "worm blobs" that have both solid and liquid-like properties. Previous research has shown that incorporating similarly intertwined chains of molecules, known as "entanglements," can make them tougher.

Their new printing method, known as CLEAR (for Continuous-curing after Light Exposure Aided by Redox initiation), follows a series of steps to entangle long molecules inside 3D-printed materials much like those intertwined worms.

When the team stretched and weight-loaded those materials in the lab (one researcher even ran over a sample with her bike) they found them to be exponentially tougher than materials printed with a standard method of 3D printing known as Digital Light Processing (DLP). Better yet: They also conformed and stuck to animal tissues and organs.

"We can now 3D print adhesive materials that are strong enough to mechanically support tissue," said co-first author Matt Davidson, a research associate in the Burdick Lab. "We have never been able to do that before."

Revolutionizing care

Burdick imagines a day when such 3D-printed materials could be used to repair defects in hearts, deliver tissue-regenerating drugs directly to organs or cartilage, restrain bulging discs or even stitch people up in the operating room without inflicting tissue damage like a needle and suture can.

His lab has filed for a provisional patent and plans to launch more studies soon to better understand how tissues react to the presence of such materials.

But the team stresses that their new method could have impacts far beyond medicine -- in research and manufacturing too. For instance, their method eliminates the need for additional energy to cure, or harden, parts, making the 3D printing process more environmentally friendly.

Read more at Science Daily

Artificial cartilage with the help of 3D printing

Is it possible to grow tissue in the laboratory, for example to replace injured cartilage? At TU Wien (Vienna), an important step has now been taken towards creating replacement tissue in the lab -- using a technique that differs significantly from other methods used around the world.

A special high-resolution 3D printing process is used to create tiny, porous spheres made of biocompatible and degradable plastic, which are then colonized with cells.

These spheroids can then be arranged in any geometry, and the cells of the different units combine seamlessly to form a uniform, living tissue.

Cartilage tissue, with which the concept has now been demonstrated at TU Wien, was previously considered particularly challenging in this respect.

Tiny spherical cages as a scaffold for the cells

"Cultivating cartilage cells from stem cells is not the biggest challenge. The main problem is that you usually have little control over the shape of the resulting tissue," says Oliver Kopinski-Grünwald from the Institute of Materials Science and Technology at TU Wien, one of the authors of the current study.

"This is also due to the fact that such stem cell clumps change their shape over time and often shrink."

To prevent this, the research team at TU Wien is working with a new approach: specially developed laser-based high-resolution 3D printing systems are used to create tiny cage-like structures that look like mini footballs and have a diameter of just a third of a millimeter.

They serve as a support structure and form compact building blocks that can then be assembled into any shape.

Stem cells are first introduced into these football-shaped mini-cages, which quickly fill the tiny volume completely.

"In this way, we can reliably produce tissue elements in which the cells are evenly distributed and the cell density is very high. This would not have been possible with previous approaches," explains Prof.

Aleksandr Ovsianikov, head of the 3D Printing and Biofabrication research group at TU Wien.

Growing together perfectly

The team used differentiated stem cells -- i.e. stem cells that can no longer develop into any type of tissue, but are already predetermined to form a specific type of tissue, in this case cartilage tissue.

Such cells are particularly interesting for medical applications, but the construction of larger tissue is challenging when it comes to cartilage cells.

In cartilage tissue, the cells form a very pronounced extracellular matrix, a mesh-like structure between the cells that often prevents different cell spheroids from growing together in the desired way.

If the 3D-printed porous spheres are colonized with cells in the desired way, the spheres can be arranged in any desired shape.

The crucial question is now: do the cells of different spheroids also combine to form a uniform, homogeneous tissue?

"This is exactly what we have now been able to show for the first time," says Kopinski-Grünwald.

"Under the microscope, you can see very clearly: neighboring spheroids grow together, the cells migrate from one spheroid to the other and vice versa, they connect seamlessly and result in a closed structure without any cavities -- in contrast to other methods that have been used so far, in which visible interfaces remain between neighboring cell clumps."

The tiny 3D-printed scaffolds give the overall structure mechanical stability while the tissue continues to mature.

Over a period of a few months, the plastic structures degrade, they simply disappear, leaving behind the finished tissue in the desired shape.

First step towards medical application

In principle, the new approach is not limited to cartilage tissue, it could also be used to tailor different kinds of larger tissues such as bone tissue.

However, there are still a few tasks to be solved along the way -- after all, unlike in cartilage tissue, blood vessels would also have to be incorporated for these tissues above a certain size.

Read more at Science Daily

Researchers 3D-print functional human brain tissue

A team of University of Wisconsin-Madison scientists has developed the first 3D-printed brain tissue that can grow and function like typical brain tissue.

It's an achievement with important implications for scientists studying the brain and working on treatments for a broad range of neurological and neurodevelopmental disorders, such as Alzheimer's and Parkinson's disease.

"This could be a hugely powerful model to help us understand how brain cells and parts of the brain communicate in humans," says Su-Chun Zhang, professor of neuroscience and neurology at UW-Madison's Waisman Center.

"It could change the way we look at stem cell biology, neuroscience, and the pathogenesis of many neurological and psychiatric disorders."

Printing methods have limited the success of previous attempts to print brain tissue, according to Zhang and Yuanwei Yan, a scientist in Zhang's lab.

The group behind the new 3D-printing process described their method today in the journal Cell Stem Cell.

Instead of using the traditional 3D-printing approach, stacking layers vertically, the researchers went horizontally.

They situated brain cells, neurons grown from induced pluripotent stem cells, in a softer "bio-ink" gel than previous attempts had employed.

"The tissue still has enough structure to hold together but it is soft enough to allow the neurons to grow into each other and start talking to each other," Zhang says.

The cells are laid next to each other like pencils laid next to each other on a tabletop.

"Our tissue stays relatively thin and this makes it easy for the neurons to get enough oxygen and enough nutrients from the growth media," Yan says.

The results speak for themselves -- which is to say, the cells can speak to each other.

The printed cells reach through the medium to form connections inside each printed layer as well as across layers, forming networks comparable to human brains.

The neurons communicate, send signals, interact with each other through neurotransmitters, and even form proper networks with support cells that were added to the printed tissue.

"We printed the cerebral cortex and the striatum and what we found was quite striking," Zhang says.

"Even when we printed different cells belonging to different parts of the brain, they were still able to talk to each other in a very special and specific way."

The printing technique offers precision -- control over the types and arrangement of cells -- not found in brain organoids, miniature organs used to study brains.

The organoids grow with less organization and control.

"Our lab is very special in that we are able to produce pretty much any type of neurons at any time. Then we can piece them together at almost any time and in whatever way we like," Zhang says.

"Because we can print the tissue by design, we can have a defined system to look at how our human brain network operates. We can look very specifically at how the nerve cells talk to each other under certain conditions because we can print exactly what we want."

That specificity provides flexibility. The printed brain tissue could be used to study signaling between cells in Down syndrome, interactions between healthy tissue and neighboring tissue affected by Alzheimer's, testing new drug candidates, or even watching the brain grow.

"In the past, we have often looked at one thing at a time, which means we often miss some critical components. Our brain operates in networks. We want to print brain tissue this way because cells do not operate by themselves. They talk to each other. This is how our brain works and it has to be studied all together like this to truly understand it," Zhang says.

"Our brain tissue could be used to study almost every major aspect of what many people at the Waisman Center are working on. It can be used to look at the molecular mechanisms underlying brain development, human development, developmental disabilities, neurodegenerative disorders, and more."

The new printing technique should also be accessible to many labs.

It does not require special bio-printing equipment or culturing methods to keep the tissue healthy, and can be studied in depth with microscopes, standard imaging techniques and electrodes already common in the field.

The researchers would like to explore the potential of specialization, though, further improving their bio-ink and refining their equipment to allow for specific orientations of cells within their printed tissue..

"Right now, our printer is a benchtop commercialized one," Yan says.

Read more at Science Daily

Scientists 3D-print hair follicles in lab-grown skin

A team led by scientists at Rensselaer Polytechnic Institute has 3D-printed hair follicles in human skin tissue cultured in the lab. This marks the first time researchers have used the technology to generate hair follicles, which play an important role in skin healing and function.

The finding, published in the journal Science Advances, has potential applications in regenerative medicine and drug testing, though engineering skin grafts that grow hair are still several years away.

"Our work is a proof-of-concept that hair follicle structures can be created in a highly precise, reproducible way using 3D-bioprinting. This kind of automated process is needed to make future biomanufacturing of skin possible," said Pankaj Karande, Ph.D., an associate professor of chemical and biological engineering and a member of Rensselaer's Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies, who led the study.

"The reconstruction of hair follicles using human-derived cells has historically been a challenge. Some studies have shown that if these cells are cultured in a three-dimensional environment, they can potentially originate new hair follicles or hair shafts, and our study builds on this work," Karande said.

When it comes to engineering human skin, hair may at first seem superfluous. However, hair follicles are quite important: They produce sweat, helping regulate body temperature, and they contain stem cells that help skin heal.

Hair follicles are also an entry point for topical drugs and cosmetics, making them an important part of dermatological testing. But today, initial safety testing is done on engineered skin tissues that lack hair follicles.

"Right now, contemporary skin models -- the engineered structures that mimic human skin -- are quite simple. Increasing their complexity by adding hair follicles would give us even more information about how skin interacts with topical products," said Carolina Catarino, Ph.D., first author of the study, who earned her doctorate at Rensselaer and is now a researcher developing new skin testing methods at Grupo Boticário, a cosmetics company in her home country of Brazil.

"Dr. Karande's lab is at the forefront of skin tissue engineering. This team has already successfully printed skin with working blood vessels, and this latest research is an exciting next step in developing and testing better treatments for burns and other skin conditions," said Deepak Vashishth, Ph.D., director of the Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies.

"Dr. Karande's work is a great example of advances being made by RPI researchers at the interface of engineering and life sciences with impact on human health," said Shekhar Garde, Ph.D., dean of Rensselaer's School of Engineering. "Bringing multichannel 3-D printing to biological realm is opening exciting opportunities that would have been hard to imagine in the past."

The researchers created their follicle-bearing skin with 3D-printing techniques adapted for printing at the cellular level.

The scientists begin by allowing samples of skin and follicle cells to divide and multiply in the lab until there are enough printable cells. Next, the researchers mix each type of cell with proteins and other materials to create the "bio-ink" used by the printer. Using an extremely thin needle to deposit the bio-ink, the printer builds the skin layer by layer, while also creating channels for depositing the hair cells. Over time, the skin cells migrate to these channels surrounding the hair cells, mirroring the follicle structures present in real skin.

Read more at Science Daily

Printed robots with bones, ligaments, and tendons

3D printing is advancing rapidly, and the range of materials that can be used has expanded considerably. While the technology was previously limited to fast-curing plastics, it has now been made suitable for slow-curing plastics as well. These have decisive advantages as they have enhanced elastic properties and are more durable and robust.

The use of such polymers is made possible by a new technology developed by researchers at ETH Zurich and a US start-up. As a result, researchers can now 3D print complex, more durable robots from a variety of high-quality materials in one go. This new technology also makes it easy to combine soft, elastic, and rigid materials. The researchers can also use it to create delicate structures and parts with cavities as desired.

Materials that return to their original state

Using the new technology, researchers at ETH Zurich have succeeded for the first time in printing a robotic hand with bones, ligaments and tendons made of different polymers in one go. "We wouldn't have been able to make this hand with the fast-curing polyacrylates we've been using in 3D printing so far," explains Thomas Buchner, a doctoral student in the group of ETH Zurich robotics professor Robert Katzschmann and first author of the study. "We're now using slow-curing thiolene polymers. These have very good elastic properties and return to their original state much faster after bending than polyacrylates." This makes thiolene polymers ideal for producing the elastic ligaments of the robotic hand.

In addition, the stiffness of thiolenes can be fine-tuned very well to meet the requirements of soft robots. "Robots made of soft materials, such as the hand we developed, have advantages over conventional robots made of metal. Because they're soft, there is less risk of injury when they work with humans, and they are better suited to handling fragile goods," Katzschmann explains.

Scanning instead of scraping

3D printers typically produce objects layer by layer: nozzles deposit a given material in viscous form at each point; a UV lamp then cures each layer immediately. Previous methods involved a device that scraped off surface irregularities after each curing step. This works only with fast-curing polyacrylates. Slow-curing polymers such as thiolenes and epoxies would gum up the scraper.

To accommodate the use of slow-curing polymers, the researchers developed 3D printing further by adding a 3D laser scanner that immediately checks each printed layer for any surface irregularities. "A feedback mechanism compensates for these irregularities when printing the next layer by calculating any necessary adjustments to the amount of material to be printed in real time and with pinpoint accuracy," explains Wojciech Matusik, a professor at the Massachusetts Institute of Technology (MIT) in the US and co-author of the study. This means that instead of smoothing out uneven layers, the new technology simply takes the unevenness into account when printing the next layer.

Inkbit, an MIT spin-off, was responsible for developing the new printing technology. The ETH Zurich researchers developed several robotic applications and helped optimise the printing technology for use with slow-curing polymers. The researchers from Switzerland and the US have now jointly published the technology and their sample applications in the journal Nature.

Read more at Science Daily

To advance space colonization, new research explores 3D printing in microgravity

Research from West Virginia University students and faculty into how 3D printing works in a weightless environment aims to support long-term exploration and habitation on spaceships, the moon or Mars.

Extended missions in outer space require the manufacture of crucial materials and equipment onsite, rather than transporting those items from Earth. Members of the Microgravity Research Team said they believe 3D printing is the way to make that happen.

The team's recent experiments focused on how a weightless microgravity environment affects 3D printing using titania foam, a material with potential applications ranging from UV blocking to water purification. ACS Applied Materials and Interfaces published their findings.

"A spacecraft can't carry infinite resources, so you have to maintain and recycle what you have and 3D printing enables that," said lead author Jacob Cordonier, a doctoral student in mechanical and aerospace engineering at the WVU Benjamin M. Statler College of Engineering and Mineral Resources. "You can print only what you need, reducing waste. Our study looked at whether a 3D-printed titanium dioxide foam could protect against ultraviolet radiation in outer space and purify water.

"The research also allows us to see gravity's role in how the foam comes out of the 3D printer nozzle and spreads onto a substrate. We've seen differences in the filament shape when printed in microgravity compared to Earth gravity. And by changing additional variables in the printing process, such as writing speed and extrusion pressure, we're able to paint a clearer image of how all these parameters interact to tune the shape of the filament."

Cordonier's co-authors include current and former undergraduate students Kyleigh Anderson, Ronan Butts, Ross O'Hara, Renee Garneau and Nathanael Wimer. Also contributing to the paper were John Kuhlman, professor emeritus, and Konstantinos Sierros, associate professor and associate chair for research in the Department of Mechanical and Aerospace Engineering.

Sierros has overseen the Microgravity Research Team's titania foam studies since 2016. The work now happens in his WVU labs but originally required taking a ride on a Boeing 727. There, students printed lines of foam onto glass slides during 20-second periods of weightlessness when the jet was at the top of its parabolic flight path.

"Transporting even a kilogram of material in space is expensive and storage is limited, so we're looking into what is called 'in-situ resource utilization,'" Sierros said. "We know the moon contains deposits of minerals very similar to the titanium dioxide used to make our foam, so the idea is you don't have to transport equipment from here to space because we can mine those resources on the moon and print the equipment that's necessary for a mission."

Necessary equipment includes shields against ultraviolet light, which poses a threat to astronauts, electronics and other space assets.

"On Earth, our atmosphere blocks a significant part of UV light -- though not all of it, which is why we get sunburned," Cordonier said. "In space or on the moon, there's nothing to mitigate it besides your spacesuit or whatever coating is on your spacecraft or habitat."

To measure titania foam's effectiveness at blocking UV waves, "we would shine light ranging from the ultraviolet wavelengths up to the visible light spectrum," he explained. "We measured how much light was getting through the titania foam film we had printed, how much got reflected back and how much was absorbed by the sample. We showed the film blocks almost all the UV light hitting the sample and very little visible light gets through. Even at only 200 microns thick, our material is effective at blocking UV radiation."

Cordonier said the foam also demonstrated photocatalytic properties, meaning that it can use light to promote chemical reactions that can do things like purify air or water.

Team member Butts, an undergraduate from Wheeling, led experiments in contact angle testing to analyze how changes in temperature affected the foam's surface energy. Butts called the research "a different type of challenge that students don't always get to experience," and said he especially valued the engagement component.

"Our team gets to do a lot of outreach with young students like the Scouts through the Merit Badge University at WVU. We get to show them what we do here as a way to say, 'Hey, this is something you could do, too,'" Butts said.

According to Sierros, "We're trying to integrate research into student careers at an early point. We have a student subgroup that's purely hardware and they make the 3D printers. We have students leading materials development, automation, data analysis. The undergraduates who have been doing this work with the support of two very competitive NASA grants are participating in the whole research process. They have published peer-reviewed scientific articles and presented at conferences."

Garneau, a student researcher from Winchester, Virginia, said her dream is for their 3D printer -- custom designed to be compact and automated -- to take a six-month trip to the International Space Station. That would enable more extensive monitoring of the printing process than was possible during the 20-second freefalls.

"This was an amazing experience," Garneau said. "It was the first time I participated in a research project that didn't have predetermined results like what I have experienced in research-based classes. It was really rewarding to analyze the data and come to conclusions that weren't based on fixed expectations.

Read more at Science Daily

Custom, 3D-printed heart replicas look and pump just like the real thing

No two hearts beat alike. The size and shape of the the heart can vary from one person to the next. These differences can be particularly pronounced for people living with heart disease, as their hearts and major vessels work harder to overcome any compromised function.

MIT engineers are hoping to help doctors tailor treatments to patients' specific heart form and function, with a custom robotic heart. The team has developed a procedure to 3D print a soft and flexible replica of a patient's heart. They can then control the replica's action to mimic that patient's blood-pumping ability.

The procedure involves first converting medical images of a patient's heart into a three-dimensional computer model, which the researchers can then 3D print using a polymer-based ink. The result is a soft, flexible shell in the exact shape of the patient's own heart. The team can also use this approach to print a patient's aorta -- the major artery that carries blood out of the heart to the rest of the body.

To mimic the heart's pumping action, the team has fabricated sleeves similar to blood pressure cuffs that wrap around a printed heart and aorta. The underside of each sleeve resembles precisely patterned bubble wrap. When the sleeve is connected to a pneumatic system, researchers can tune the outflowing air to rhythmically inflate the sleeve's bubbles and contract the heart, mimicking its pumping action.

The researchers can also inflate a separate sleeve surrounding a printed aorta to constrict the vessel. This constriction, they say, can be tuned to mimic aortic stenosis -- a condition in which the aortic valve narrows, causing the heart to work harder to force blood through the body.

Doctors commonly treat aortic stenosis by surgically implanting a synthetic valve designed to widen the aorta's natural valve. In the future, the team says that doctors could potentially use their new procedure to first print a patient's heart and aorta, then implant a variety of valves into the printed model to see which design results in the best function and fit for that particular patient. The heart replicas could also be used by research labs and the medical device industry as realistic platforms for testing therapies for various types of heart disease.

"All hearts are different," says Luca Rosalia, a graduate student in the MIT-Harvard Program in Health Sciences and Technology. "There are massive variations, especially when patients are sick. The advantage of our system is that we can recreate not just the form of a patient's heart, but also its function in both physiology and disease."

Rosalia and his colleagues report their results in a study appearing today in Science Robotics. MIT co-authors include Caglar Ozturk, Debkalpa Goswami, Jean Bonnemain, Sophie Wang, and Ellen Roche, along with Benjamin Bonner of Massachusetts General Hospital, James Weaver of Harvard University, and Christopher Nguyen, Rishi Puri, and Samir Kapadia at the Cleveland Clinic in Ohio.

Print and pump

In January 2020, team members, led by mechanical engineering professor Ellen Roche, developed a "biorobotic hybrid heart" -- a general replica of a heart, made from synthetic muscle containing small, inflatable cylinders, which they could control to mimic the contractions of a real beating heart.

Shortly after those efforts, the Covid-19 pandemic forced Roche's lab, along with most others on campus, to temporarily close. Undeterred, Rosalia continued tweaking the heart-pumping design at home.

"I recreated the whole system in my dorm room that March," Rosalia recalls.

Months later, the lab reopened, and the team continued where it left off, working to improve the control of the heart-pumping sleeve, which they tested in animal and computational models. They then expanded their approach to develop sleeves and heart replicas that are specific to individual patients. For this, they turned to 3D printing.

"There is a lot of interest in the medical field in using 3D printing technology to accurately recreate patient anatomy for use in preprocedural planning and training," notes Wang, who is a vascular surgery resident at Beth Israel Deaconess Medical Center in Boston.

An inclusive design

In the new study, the team took advantage of 3D printing to produce custom replicas of actual patients' hearts. They used a polymer-based ink that, once printed and cured, can squeeze and stretch, similarly to a real beating heart.

As their source material, the researchers used medical scans of 15 patients diagnosed with aortic stenosis. The team converted each patient's images into a three-dimensional computer model of the patient's left ventricle (the main pumping chamber of the heart) and aorta. They fed this model into a 3D printer to generate a soft, anatomically accurate shell of both the ventricle and vessel.

The team also fabricated sleeves to wrap around the printed forms. They tailored each sleeve's pockets such that, when wrapped around their respective forms and connected to a small air pumping system, the sleeves could be tuned separately to realistically contract and constrict the printed models.

The researchers showed that for each model heart, they could accurately recreate the same heart-pumping pressures and flows that were previously measured in each respective patient.

"Being able to match the patients' flows and pressures was very encouraging," Roche says. "We're not only printing the heart's anatomy, but also replicating its mechanics and physiology. That's the part that we get excited about."

Going a step further, the team aimed to replicate some of the interventions that a handful of the patients underwent, to see whether the printed heart and vessel responded in the same way. Some patients had received valve implants designed to widen the aorta. Roche and her colleagues implanted similar valves in the printed aortas modeled after each patient. When they activated the printed heart to pump, they observed that the implanted valve produced similarly improved flows as in actual patients following their surgical implants.

Finally, the team used an actuated printed heart to compare implants of different sizes, to see which would result in the best fit and flow -- something they envision clinicians could potentially do for their patients in the future.

"Patients would get their imaging done, which they do anyway, and we would use that to make this system, ideally within the day," says co-author Nyugen. "Once it's up and running, clinicians could test different valve types and sizes and see which works best, then use that to implant."

Ultimately, Roche says the patient-specific replicas could help develop and identify ideal treatments for individuals with unique and challenging cardiac geometries.

Read more at Science Daily

Martian rock-metal composite shows potential of 3D printing on Mars

A small amount of simulated crushed Martian rock mixed with a titanium alloy made a stronger, high-performance material in a 3D-printing process that could one day be used on Mars to make tools or rocket parts. The parts were made by Washington State University researchers with as little as 5% up to 100% Martian regolith, a black powdery substance meant to mimic the rocky, inorganic material found on the surface of the red planet. While the parts with 5% Martian regolith were strong, the 100% regolith parts proved brittle and cracked easily. Still, even high-Martian content materials would be useful in making coatings to protect equipment from rust or radiation damage.

A little Martian dust appears to go a long way. A small amount of simulated crushed Martian rock mixed with a titanium alloy made a stronger, high-performance material in a 3D-printing process that could one day be used on Mars to make tools or rocket parts.

The parts were made by Washington State University researchers with as little as 5% up to 100% Martian regolith, a black powdery substance meant to mimic the rocky, inorganic material found on the surface of the red planet.

While the parts with 5% Martian regolith were strong, the 100% regolith parts proved brittle and cracked easily. Still, even high-Martian content materials would be useful in making coatings to protect equipment from rust or radiation damage, said Amit Bandyopadhyay, corresponding author on the study published in the International Journal of Applied Ceramic Technology.

"In space, 3D printing is something that has to happen if we want to think of a manned mission because we really cannot carry everything from here," said Bandyopadhyay, a professor in WSU's School of Mechanical and Materials Engineering. "And if we forgot something, we cannot come back to get it."

Bringing materials into space can be extremely expensive. For instance, the authors noted it costs about $54,000 for the NASA space shuttle to put just one kilogram of payload (about 2.2 pounds) into Earth orbit. Anything that can be made in space, or on planet, would save weight and money -- not to mention if something breaks, astronauts would need a way to repair it on site.

Bandyopadhyay first demonstrated the feasibility of this idea in 2011 when his team used 3D-printing to manufacture parts from lunar regolith, simulated crushed moon rock, for NASA. Since then, space agencies have embraced the technology, and International Space Station has its own 3D-printers to manufacture needed materials on site and for experiments.

For this study, Bandyopadhyay along with graduate students Ali Afrouzian and Kellen Traxel, used a powder-based 3D printer to mix the simulated Martian rock dust with a titanium alloy, a metal often used in space exploration for its strength and heat-resistant properties. As part of the process, a high-powered laser heated the materials to over 2,000 degrees Celsius (3,632 F). Then, the melted mix of Martian regolith-ceramic and metal material flowed onto a moving platform that allowed the researchers to create different sizes and shapes. After the material cooled down, the researchers tested it for strength and durability.

The ceramic material made from 100% Martian rock dust cracked as it cooled, but as Bandyopadhyay pointed out it could still make good coatings for radiation shields as cracks do not matter in that context. But just a little Martian dust, the mixture with 5% regolith, not only did not crack or bubble but also exhibited better properties than the titanium alloy alone, which meant it could be used to make lighter weight pieces that could still bear heavy loads.

"It gives you a better, higher strength and hardness material, so that can perform significantly better in some applications," he said.

This study is just a start, Bandyopadhyay said, and future research may yield better composites using different metals or 3D-printing techniques.

Read more at Science Daily

Researchers 3D print sensors for satellites

MIT scientists have created the first completely digitally manufactured plasma sensors for orbiting spacecraft. These plasma sensors, also known as retarding potential analyzers (RPAs), are used by satellites to determine the chemical composition and ion energy distribution of the atmosphere.

The 3D-printed and laser-cut hardware performed as well as state-of-the-art semiconductor plasma sensors that are manufactured in a cleanroom, which makes them expensive and requires weeks of intricate fabrication. By contrast, the 3D-printed sensors can be produced for tens of dollars in a matter of days.

Due to their low cost and speedy production, the sensors are ideal for CubeSats. These inexpensive, low-power, and lightweight satellites are often used for communication and environmental monitoring in Earth's upper atmosphere.

The researchers developed RPAs using a glass-ceramic material that is more durable than traditional sensor materials like silicon and thin-film coatings. By using the glass-ceramic in a fabrication process that was developed for 3D printing with plastics, there were able to create sensors with complex shapes that can withstand the wide temperature swings a spacecraft would encounter in lower Earth orbit.

"Additive manufacturing can make a big difference in the future of space hardware. Some people think that when you 3D-print something, you have to concede less performance. But we've shown that is not always the case. Sometimes there is nothing to trade off," says Luis Fernando Velásquez-García, a principal scientist in MIT's Microsystems Technology Laboratories (MTL) and senior author of a paper presenting the plasma sensors.

Joining Velásquez-García on the paper are lead author and MTL postdoc Javier Izquierdo-Reyes; graduate student Zoey Bigelow; and postdoc Nicholas K. Lubinsky. The research is published in Additive Manufacturing.

Versatile sensors

An RPA was first used in a space mission in 1959. The sensors detect the energy in ions, or charged particles, that are floating in plasma, which is a superheated mix of molecules present in the Earth's upper atmosphere. Aboard an orbiting spacecraft like a CubeSat, the versatile instruments measure energy and conduct chemical analyses that can help scientists predict the weather or monitor climate change.

The sensors contain a series of electrically charged meshes dotted with tiny holes. As plasma passes through the holes, electrons and other particles are stripped away until only ions remain. These ions create an electric current that the sensor measures and analyzes.

Key to the success of an RPA is the housing structure that aligns the meshes. It must be electrically insulating while also able to withstand sudden, drastic swings in temperature. The researchers used a printable, glass-ceramic material that displays these properties, known as Vitrolite.

Pioneered in the early 20th century, Vitrolite was often used in colorful tiles that became a common sight in art deco buildings.

The durable material can also withstand temperatures as high as 800 degrees Celsius without breaking down, whereas polymers used in semiconductor RPAs start to melt at 400 degrees Celsius.

"When you make this sensor in the cleanroom, you don't have the same degree of freedom to define materials and structures and how they interact together. What made this possible is the latest developments in additive manufacturing," Velásquez-García says.

Rethinking fabrication

The 3D printing process for ceramics typically involves ceramic powder that is hit with a laser to fuse it into shapes, but this process often leaves the material coarse and creates weak points due to the high heat from the lasers.

Instead, the MIT researchers used vat polymerization, a process introduced decades ago for additive manufacturing with polymers or resins. With vat polymerization, a 3D structure is built one layer at a time by submerging it repeatedly into a vat of liquid material, in this case Vitrolite. Ultraviolet light is used to cure the material after each layer is added, and then the platform is submerged in the vat again. Each layer is only 100 microns thick (roughly the diameter of a human hair), enabling the creation of smooth, pore-free, complex ceramic shapes.

In digital manufacturing, objects described in a design file can be very intricate. This precision allowed the researchers to create laser-cut meshes with unique shapes so the holes lined up perfectly when they were set inside the RPA housing. This enables more ions to pass through, which leads to higher-resolution measurements.

Because the sensors were cheap to produce and could be fabricated so quickly, the team prototyped four unique designs.

While one design was especially effective at capturing and measuring a wide range of plasmas, like those a satellite would encounter in orbit, another was well-suited for sensing extremely dense and cold plasmas, which are typically only measurable using ultraprecise semiconductor devices.

This high precision could enable 3D-printed sensors for applications in fusion energy research or supersonic flight. The rapid prototyping process could even spur more innovation in satellite and spacecraft design, Velásquez-García adds.

"If you want to innovate, you need to be able to fail and afford the risk. Additive manufacturing is a very different way to make space hardware. I can make space hardware and if it fails, it doesn't matter because I can make a new version very quickly and inexpensively, and really iterate on the design. It is an ideal sandbox for researchers," he says.

While Velásquez-García is pleased with these sensors, in the future he wants to enhance the fabrication process. Reducing the thickness of layers or pixel size in glass-ceramic vat polymerization could create complex hardware that is even more precise. Moreover, fully additively manufacturing the sensors would make them compatible with in-space manufacturing. He also wants to explore the use of artificial intelligence to optimize sensor design for specific use cases, such as greatly reducing their mass while ensuring they remain structurally sound.

Read more at Science Daily

Silk fibers improve bioink for 3D-printed artificial tissues and organs

 How do you test, in early-stage research, whether a potential pharmaceutical effectively targets a human tumor, organ, or some other part of the body? How do you grow a new hand or some other body part? Researchers are in the early stages of using 3D cell printing technology to make developments like these happen. A standard way -- currently unavailable -- to fix the cells in place after printing would help researchers avoid having to 'reinvent the wheel' in every new investigation.

In a study recently published in Materials Today Bio, researchers from Osaka University have used silk nanofibers obtained by mechanical disintegration to enhance the printing process without damaging the cells or cell assemblies. An attractive point of silk for this application is that silk is believed to be a safe material for humans. This development will help bring 3D cell printing research out of the laboratory and into real-world biomedical use.

To obtain the fibers, the researchers started with virgin silk, then removed the protein sericin from it because this protein causes inflammation in patients. Next, the researchers ground the remaining biocompatible material into nanofibers. The fibers can be sterilized -- without damaging them -- for medical use, with common laboratory equipment.

"Our silk fibers are excellent additives to bioink cell printing media," says lead author Shinji Sakai. "They are compatible with many media, such as those containing gelatin, chitosan, or hyaluronic acid, giving them a broad range of potential applications."

The main purpose of the fibers was to ensure that the cells in the bioink retained their 3D positioning after printing without damaging the cells. The fibers fulfill this purpose by enhancing the integrity of the bioink and minimizing the damaging high mechanical stresses often placed on cells during printing.

"Various mechanical experiments say the same thing: the nanofibers enhanced the properties of the printing media," explains Professor Sakai. "For example, Young's modulus -- a measure of stiffness -- increased several-fold and remained enhanced for over a month."

The fibers help printed configurations retain their structural integrity after printing. For example, a nose-shaped configuration retained its shape only when printed with bioink containing the silk fibers. Over 85% of the cells in the bioink remained alive after a week in the printed bioink with or without the added fibers, indicating that adding the fibers did not damage the cells.

Read more at Science Daily

Researchers develop simple method to 3D print milk products

 Researchers from the Singapore University of Technology and Design (SUTD) developed a method to perform direct ink writing (DIW) 3D printing of milk-based products at room temperature, while maintaining its temperature sensitive nutrients.

3D printing of food has been achieved by different printing methods, including the widely used selective laser sintering (SLS) and hot-melt extrusion methods. However, these methods are not always compatible with temperature-sensitive nutrients found in certain types of food. For instance, milk is rich in both calcium and protein, but as these nutrients are temperature sensitive, milk is unsuitable for 3D printing using the aforementioned printing methods which require high temperature. While the cold-extrusion is a viable alternative, it often requires rheology modifiers or additives to stabilize printed structures. Optimizing these additives is a complex and judicious task.

To tackle these limitations, the research team from SUTD's Soft Fluidics Lab changed the rheological properties of the printing ink and demonstrated DIW 3D printing of milk by cold-extrusion with a single milk product -- powdered milk. The team found that the concentration of milk powder allowed for the simple formulation of 3D-printable milk inks using water to control the rheology. Extensive characterizations of the formulated milk ink were also conducted to analyse their rheological properties and ensure optimal printability.

"This novel yet simple method can be used in formulating various nutritious foods including those served to patients in hospitals for their special dietary needs," said the lead author and Ph.D. candidate from SUTD, Mr Lee Cheng Pau.

"Cold-extrusion does not compromise heat-sensitive nutrients and yet offers vast potential in 3D printing of aesthetically pleasing, nutritionally controlled foods customized for individual requirements," added Assistant Professor Michinao Hashimoto, the principal investigator of the study.

From Science Daily

Living skin can now be 3D-printed with blood vessels included

Researchers at Rensselaer Polytechnic Institute have developed a way to 3D print living skin, complete with blood vessels. The advancement, published online today in Tissue Engineering Part A, is a significant step toward creating grafts that are more like the skin our bodies produce naturally.

"Right now, whatever is available as a clinical product is more like a fancy Band-Aid," said Pankaj Karande, an associate professor of chemical and biological engineering and member of the Center for Biotechnology and Interdisciplinary Studies (CBIS), who led this research at Rensselaer. "It provides some accelerated wound healing, but eventually it just falls off; it never really integrates with the host cells."

A significant barrier to that integration has been the absence of a functioning vascular system in the skin grafts.

Karande has been working on this challenge for several years, previously publishing one of the first papers showing that researchers could take two types of living human cells, make them into "bio-inks," and print them into a skin-like structure. Since then, he and his team have been working with researchers from Yale School of Medicine to incorporate vasculature.

In this paper, the researchers show that if they add key elements -- including human endothelial cells, which line the inside of blood vessels, and human pericyte cells, which wrap around the endothelial cells -- with animal collagen and other structural cells typically found in a skin graft, the cells start communicating and forming a biologically relevant vascular structure within the span of a few weeks. You can watch Karande explain this development here.

"As engineers working to recreate biology, we've always appreciated and been aware of the fact that biology is far more complex than the simple systems we make in the lab," Karande said. "We were pleasantly surprised to find that, once we start approaching that complexity, biology takes over and starts getting closer and closer to what exists in nature."

Once the Yale team grafted it onto a special type of mouse, the vessels from the skin printed by the Rensselaer team began to communicate and connect with the mouse's own vessels.

"That's extremely important, because we know there is actually a transfer of blood and nutrients to the graft which is keeping the graft alive," Karande said.

In order to make this usable at a clinical level, researchers need to be able to edit the donor cells using something like the CRISPR technology, so that the vessels can integrate and be accepted by the patient's body.

"We are still not at that step, but we are one step closer," Karande said.

"This significant development highlights the vast potential of 3D bioprinting in precision medicine, where solutions can be tailored to specific situations and eventually to individuals," said Deepak Vashishth, the director CBIS. "This is a perfect example of how engineers at Rensselaer are solving challenges related to human health."

Karande said more work will need to be done to address the challenges associated with burn patients, which include the loss of nerve and vascular endings. But the grafts his team has created bring researchers closer to helping people with more discrete issues, like diabetic or pressure ulcers.

Read more at Science Daily

3-D printed coral could help endangered reefs

Natural disasters such as hurricanes often leave devastation in their wake. Residents living in affected areas are sometimes displaced or require temporary shelter while their homes -- or even neighborhoods -- are repaired or rebuilt.

But what if you are a fish and your home is a coral reef?

Researchers across the globe are searching for ways to help endangered reefs, and the animals that live there, withstand or recover from weather events, including bleaching and storms that can occur with increasingly warmer water temperatures.

One idea is to use 3D-printed coral models to replace or supplement coral reef systems that have been affected.

New research by the University of Delaware's Danielle Dixson and UD alumnus Emily Ruhl has shown that 3D-printed objects do not impact the behavior of coral-associated damselfish or the survival of a settling stony coral.

Further, the study demonstrated that fish showed no preference between materials used to 3D-print artificial corals, opening the door to using environmentally friendly materials, such as biodegradable cornstarch instead of plastic.

With mounting concerns about plastic pollution in the marine environment, it is timely evidence that can support environmentally conscious decisions about what is put in the ocean.

The researchers reported their results in PLOS One, a peer-reviewed open source journal.

Testing 3D-printed materials

Like others studying this problem, Dixson and Ruhl are looking for ways to keep the right animals on a reef after an emergency to fuel recovery. One important consideration is knowing that any 3D-printed material used won't harm coral or negatively affect fish behavior.

"If the fish on a reef won't use the 3D-printed coral models as a habitat in the wild, it could place them at greater risk for predation by other larger species," said Dixson, an associate professor in UD's College of Earth, Ocean and Environment's School of Marine Science and Policy. "If coral larvae won't settle on 3D-printed materials, they can't help to rebuild the reef."

In laboratory experiments, the researchers studied the behavior of damselfish and mustard hill coral larvae in the presence of a coral skeleton and four 3D-printed coral models made from different filaments. Blue-green damselfish (Chromis viridis) are a common coral-associated fish found in the Indian and Pacific Oceans, while mustard hill corals (Porites astreoides) are a stony coral found in the Caribbean Sea.

The 3D coral models were made by replicating a coral skeleton using 50 iPhone images of the coral taken from all angles and a 3D printer. The researchers 3D-printed four different artificial coral models from low-cost, widely available filaments, including polyester and two biodegradable materials, one made from cornstarch and another made from cornstarch combined with stainless steel powder.

The researchers placed the damselfish into a fish tank loaded with the coral skeleton and the four artificial habitat options, in what is known as a cafeteria-style choice experiment, and studied whether the fish preferred one habitat over another.

Behavior analysis showed the damselfish did not display a preference between the native coral skeleton and the 3D-printed coral materials. The fish's activity level, such as frequency of movement and distance the fish traveled in the tank, also remained unchanged regardless of what coral habitat they were provided.

Ruhl said she was surprised that the fish behaved the same near artificial coral even with a natural coral skeleton present.

"I thought the natural skeleton would elicit more docile (that is, accepting) behavior compared to 3D-printed objects," said Ruhl, who earned her master's degree in marine biosciences at UD in 2018. "But then we realized the small reef fish didn't care if the habitat was artificial or calcium carbonate, they just wanted protection."

The researchers' lab experiments also revealed that mustard hill coral larvae settled at much higher rates on 3D-printed surfaces compared to having no settlement surface at all, which could occur if a reef were flattened in a storm.

This is promising news since both reef-associated fish and coral are vulnerable animal species, making them a good proxy for understanding how other reef organisms will respond to 3D-printed materials in the open ocean.

As coral reefs degrade, they often lose structural complexity, which is a problem for reef-associated fish that rarely move more than 15 feet from home in their entire lives. Without proper habitat, coral reef associated juvenile fish don't grow up to be bigger fish, and without bigger fish that feed on competitive algae, the algae can overgrow live corals, causing destruction and placing the whole ecosystem at risk.

In ongoing work, the researchers are analyzing field data from Fiji where they deployed 3D-printed coral and tiles made from biodegradable cornstarch filaments after determining they were safe to use. They are analyzing what settled on the artificial tiles, with an eye toward methods that would support conservation efforts.

"Offering 3D-printed habitats is a way to provide reef organisms a structural starter kit that can become part of the landscape as fish and coral build their homes around the artificial coral," Dixson said. "And since the materials we selected are biodegradable, the artificial coral would naturally degrade over time as the live coral overgrows it."

In addition, 3D-printed coral models can be useful as a control for fish-related laboratory studies, enabling researchers to provide each fish an identical habitat, something that is currently not possible with the use of coral skeletons, Dixson said.

Read more at Science Daily

Researchers revolutionize 3D printed products with data-driven design method

Additive manufacturing (AM), also known as three-dimensional printing, is a process that fabricates parts in a layer-by-layer manner by adding and processing materials. Advancements in AM technology have enabled the processing of a wide range of materials to create products in varying scales which span from medical implants to aircraft engine parts. These products, which can be rich in shape, material, hierarchical and functional complexities, offer high potential to revolutionize existing product development processes.

However, it can be a difficult process to fully realize the potential of AM's unique capabilities for product development as it requires product designers to change their design mindsets.

In conventional manufacturing processes, the main task for designers is tailoring their designs to eliminate manufacturing difficulties and minimize costs. On the contrary, AM has fewer manufacturing constraints while offering designers with much more design freedom to explore. Therefore, designers must search for optimal design solutions out of millions of design alternatives that are different in geometry, topology, structure, and material. This can be a tedious task with current design methods and computer-aided design (CAD) tools due to the lack of ability to rapidly explore and exploit such a high dimensional design space.

To address this issue, researchers from Digital Manufacturing and Design (DManD) Centre from the Singapore University of Technology and Design (SUTD) proposed a holistic approach that applies data-driven methods in design search and optimization at successive stages of a design process for AM products.

First, they used simple and computationally inexpensive surrogate models in the design exploration process to approximate and replace complex high-fidelity engineering analysis models for rapidly narrowing down the high-dimensional design space. Next, they conducted design optimization based on refined surrogate models to obtain a single optimal design. These surrogate models are trained based on an updated dataset using the Markov Chain Monte Carlo resampling method.

This design approach was demonstrated in the design of an AM fabricated ankle brace (refer to image) that has a tunable mechanical performance for facilitating the recovery process of joints. In this design, the researchers selected a metamaterial which has a horseshoe-like structure, where its stiffness can be tailored. The proposed design approach was applied to optimize the orientation and dimensions of the horseshoe-like structure's geometry in different areas to achieve desired stiffness distributions.

Such geometry complexities enabled by AM offer the ankle brace design unique and favorable behaviors. The ankle brace is very soft within the allowable range of motions which provides comfort to patients. However, once the movement is out of the permissible range, it becomes stiff enough to protect the users' joints from extreme load conditions due to its geometrical design.

"Previously, it was hard for designers to imagine a design of such complex geometry due to the limitations in conventional manufacturing, but now this design is easily achievable with AM. Our new approach allows designers to embrace the design freedom in AM that comes with the shift in design paradigm and create more optimal products similar to the ankle brace," said first author Dr. Yi Xiong, Research Fellow from SUTD.

With the design space exploration and exploitation capability developed, the research team is working towards a more ambitious goal -- to develop a next-generation CAD system for AM.

Read more at Science Daily

A swifter way towards 3D-printed organs

20 people die every day waiting for an organ transplant in the United States, and while more than 30,000 transplants are now performed annually, there are over 113,000 patients currently on organ waitlists. Artificially grown human organs are seen by many as the "holy grail" for resolving this organ shortage, and advances in 3D printing have led to a boom in using that technique to build living tissue constructs in the shape of human organs. However, all 3D-printed human tissues to date lack the cellular density and organ-level functions required for them to be used in organ repair and replacement.

Now, a new technique called SWIFT (sacrificial writing into functional tissue) created by researchers from Harvard's Wyss Institute for Biologically Inspired Engineering and John A. Paulson School of Engineering and Applied Sciences (SEAS), overcomes that major hurdle by 3D printing vascular channels into living matrices composed of stem-cell-derived organ building blocks (OBBs), yielding viable, organ-specific tissues with high cell density and function. The research is reported in Science Advances.

"This is an entirely new paradigm for tissue fabrication," said co-first author Mark Skylar-Scott, Ph.D., a Research Associate at the Wyss Institute. "Rather than trying to 3D-print an entire organ's worth of cells, SWIFT focuses on only printing the vessels necessary to support a living tissue construct that contains large quantities of OBBs, which may ultimately be used therapeutically to repair and replace human organs with lab-grown versions containing patients' own cells."

SWIFT involves a two-step process that begins with forming hundreds of thousands of stem-cell-derived aggregates into a dense, living matrix of OBBs that contains about 200 million cells per milliliter. Next, a vascular network through which oxygen and other nutrients can be delivered to the cells is embedded within the matrix by writing and removing a sacrificial ink. "Forming a dense matrix from these OBBs kills two birds with one stone: not only does it achieve a high cellular density akin to that of human organs, but the matrix's viscosity also enables printing of a pervasive network of perfusable channels within it to mimic the blood vessels that support human organs," said co-first author Sébastien Uzel, PhD., a Research Associate at the Wyss Institute and SEAS.

The cellular aggregates used in the SWIFT method are derived from adult induced pluripotent stem cells, which are mixed with a tailored extracellular matrix (ECM) solution to make a living matrix that is compacted via centrifugation. At cold temperatures (0-4oC), the dense matrix has the consistency of mayonnaise - soft enough to manipulate without damaging the cells, but thick enough to hold its shape - making it the perfect medium for sacrificial 3D printing. In this technique, a thin nozzle moves through this matrix depositing a strand of gelatin "ink" that pushes cells out of the way without damaging them.

When the cold matrix is heated to 37 oC, it stiffens to become more solid (like an omelet being cooked) while the gelatin ink melts and can be washed out, leaving behind a network of channels embedded within the tissue construct that can be perfused with oxygenated media to nourish the cells. The researchers were able to vary the diameter of the channels from 400 micrometers to 1 millimeter, and seamlessly connected them to form branching vascular networks within the tissues.

Organ-specific tissues that were printed with embedded vascular channels using SWIFT and perfused in this manner remained viable, while tissues grown without these channels experienced cell death in their cores within 12 hours. To see whether the tissues displayed organ-specific functions, the team printed, evacuated, and perfused a branching channel architecture into a matrix consisting of heart-derived cells and flowed media through the channels for over a week. During that time, the cardiac OBBs fused together to form a more solid cardiac tissue whose contractions became more synchronous and over 20 times stronger, mimicking key features of a human heart.

"Our SWIFT biomanufacturing method is highly effective at creating organ-specific tissues at scale from OBBs ranging from aggregates of primary cells to stem-cell-derived organoids," said corresponding author Jennifer Lewis, Sc.D., who is a Core Faculty Member at the Wyss Institute as well as the Hansjörg Wyss Professor of Biologically Inspired Engineering at SEAS. "By integrating recent advances from stem-cell researchers with the bioprinting methods developed by my lab, we believe SWIFT will greatly advance the field of organ engineering around the world."

Collaborations are underway with Wyss Institute faculty members Chris Chen, M.D., Ph.D. at Boston University and Sangeeta Bhatia, M.D., Ph.D., at MIT to implant these tissues into animal models and explore their host integration, as part of the 3D Organ Engineering Initiative co-led by Lewis and Chris Chen.

Read more at Science Daily

3D printing the human heart

A team of researchers from Carnegie Mellon University has published a paper in Science that details a new technique allowing anyone to 3D bioprint tissue scaffolds out of collagen, the major structural protein in the human body. This first-of-its-kind method brings the field of tissue engineering one step closer to being able to 3D print a full-sized, adult human heart.

The technique, known as Freeform Reversible Embedding of Suspended Hydrogels (FRESH), has allowed the researchers to overcome many challenges associated with existing 3D bioprinting methods, and to achieve unprecedented resolution and fidelity using soft and living materials.

Each of the organs in the human body, such as the heart, is built from specialized cells that are held together by a biological scaffold called the extracellular matrix (ECM). This network of ECM proteins provides the structure and biochemical signals that cells need to carry out their normal function. However, until now it has not been possible to rebuild this complex ECM architecture using traditional biofabrication methods.

"What we've shown is that we can print pieces of the heart out of cells and collagen into parts that truly function, like a heart valve or a small beating ventricle," says Adam Feinberg, a professor of biomedical engineering (BME) and materials science & engineering at Carnegie Mellon, whose lab performed this work. "By using MRI data of a human heart, we were able to accurately reproduce patient-specific anatomical structure and 3D bioprint collagen and human heart cells."

Over 4000 patients in the United States are waiting for a heart transplant, while millions of others worldwide need hearts but are ineligible for the waitlist. The need for replacement organs is immense, and new approaches are needed to engineer artificial organs that are capable of repairing, supplementing, or replacing long-term organ function. Feinberg, who is a member of Carnegie Mellon's Bioengineered Organs Initiative, is working to solve these challenges with a new generation of bioengineered organs that more closely replicate natural organ structures.

"Collagen is an extremely desirable biomaterial to 3D print with because it makes up literally every single tissue in your body," explains Andrew Hudson, a BME Ph.D. student in Feinberg's lab and co-first author on the paper. "What makes it so hard to 3D print, however, is that it starts out as a fluid -- so if you try to print this in air it just forms a puddle on your build platform. So we've developed a technique that prevents it from deforming."

The FRESH 3D bioprinting method developed in Feinberg's lab allows collagen to be deposited layer-by-layer within a support bath of gel, giving the collagen a chance to solidify in place before it is removed from the support bath. With FRESH, the support gel can be easily melted away by heating the gel from room temperature to body temperature after the print is complete. This way, the researchers can remove the support gel without damaging the printed structure made of collagen or cells.

This method is truly exciting for the field of 3D bioprinting because it allows collagen scaffolds to be printed at the large scale of human organs. And it is not limited to collagen, as a wide range of other soft gels including fibrin, alginate, and hyaluronic acid can be 3D bioprinted using the FRESH technique, providing a robust and adaptable tissue engineering platform. Importantly, the researchers also developed open-source designs so that nearly anyone, from medical labs to high school science classes, can build and have access to low-cost, high-performance 3D bioprinters.

Looking forward, FRESH has applications in many aspects of regenerative medicine, from wound repair to organ bioengineering, but it is just one piece of a growing biofabrication field. "Really what we're talking about is the convergence of technologies," says Feinberg. "Not just what my lab does in bioprinting, but also from other labs and small companies in the areas of stem cell science, machine learning, and computer simulation, as well as new 3D bioprinting hardware and software."

Read more at Science Daily

Organ bioprinting gets a breath of fresh air

Bioprinting research from the lab of Rice University bioengineer Jordan Miller featured a visually stunning proof-of-principle -- a scale-model of a lung-mimicking air sac with airways and blood vessels that never touch yet still provide oxygen to red blood cells.

Bioengineers have cleared a major hurdle on the path to 3D printing replacement organs with a breakthrough technique for bioprinting tissues.

The new innovation allows scientists to create exquisitely entangled vascular networks that mimic the body's natural passageways for blood, air, lymph and other vital fluids.

The research is featured on the cover of this week's issue of Science. It includes a visually stunning proof-of-principle -- a hydrogel model of a lung-mimicking air sac in which airways deliver oxygen to surrounding blood vessels. Also reported are experiments to implant bioprinted constructs containing liver cells into mice.

The work was led by bioengineers Jordan Miller of Rice University and Kelly Stevens of the University of Washington (UW) and included 15 collaborators from Rice, UW, Duke University, Rowan University and Nervous System, a design firm in Somerville, Massachusetts.

"One of the biggest road blocks to generating functional tissue replacements has been our inability to print the complex vasculature that can supply nutrients to densely populated tissues," said Miller, assistant professor of bioengineering at Rice's Brown School of Engineering. "Further, our organs actually contain independent vascular networks -- like the airways and blood vessels of the lung or the bile ducts and blood vessels in the liver. These interpenetrating networks are physically and biochemically entangled, and the architecture itself is intimately related to tissue function. Ours is the first bioprinting technology that addresses the challenge of multivascularization in a direct and comprehensive way."

Stevens, assistant professor of bioengineering in the UW College of Engineering, assistant professor of pathology in the UW School of Medicine, and an investigator at the UW Medicine Institute for Stem Cell and Regenerative Medicine, said multivascularization is important because form and function often go hand in hand.

"Tissue engineering has struggled with this for a generation," Stevens said. "With this work we can now better ask, 'If we can print tissues that look and now even breathe more like the healthy tissues in our bodies, will they also then functionally behave more like those tissues?' This is an important question, because how well a bioprinted tissue functions will affect how successful it will be as a therapy."

The goal of bioprinting healthy, functional organs is driven by the need for organ transplants. More than 100,000 people are on transplant waiting lists in the United States alone, and those who do eventually receive donor organs still face a lifetime of immune-suppressing drugs to prevent organ rejection. Bioprinting has attracted intense interest over the past decade because it could theoretically address both problems by allowing doctors to print replacement organs from a patient's own cells. A ready supply of functional organs could one day be deployed to treat millions of patients worldwide.

"We envision bioprinting becoming a major component of medicine within the next two decades," Miller said.

"The liver is especially interesting because it performs a mind-boggling 500 functions, likely second only to the brain," Stevens said. "The liver's complexity means there is currently no machine or therapy that can replace all its functions when it fails. Bioprinted human organs might someday supply that therapy."

To address this challenge, the team created a new open-source bioprinting technology dubbed the "stereolithography apparatus for tissue engineering," or SLATE. The system uses additive manufacturing to make soft hydrogels one layer at a time.

Layers are printed from a liquid pre-hydrogel solution that becomes a solid when exposed to blue light. A digital light processing projector shines light from below, displaying sequential 2D slices of the structure at high resolution, with pixel sizes ranging from 10-50 microns. With each layer solidified in turn, an overhead arm raises the growing 3D gel just enough to expose liquid to the next image from the projector. The key insight by Miller and Bagrat Grigoryan, a Rice graduate student and lead co-author of the study, was the addition of food dyes that absorb blue light. These photoabsorbers confine the solidification to a very fine layer. In this way, the system can produce soft, water-based, biocompatible gels with intricate internal architecture in a matter of minutes.

Tests of the lung-mimicking structure showed that the tissues were sturdy enough to avoid bursting during blood flow and pulsatile "breathing," a rhythmic intake and outflow of air that simulated the pressures and frequencies of human breathing. Tests found that red blood cells could take up oxygen as they flowed through a network of blood vessels surrounding the "breathing" air sac. This movement of oxygen is similar to the gas exchange that occurs in the lung's alveolar air sacs.

To design the study's most complicated lung-mimicking structure, which is featured on the cover of Science, Miller collaborated with study co-authors Jessica Rosenkrantz and Jesse Louis-Rosenberg, co-founders of Nervous System.

"When we founded Nervous System it was with the goal of adapting algorithms from nature into new ways to design products," Rosenkrantz said. "We never imagined we'd have the opportunity to bring that back and design living tissues."

In the tests of therapeutic implants for liver disease, the team 3D printed tissues, loaded them with primary liver cells and implanted them into mice. The tissues had separate compartments for blood vessels and liver cells and were implanted in mice with chronic liver injury. Tests showed that the liver cells survived the implantation.

Miller said the new bioprinting system can also produce intravascular features, like bicuspid valves that allow fluid to flow in only one direction. In humans, intravascular valves are found in the heart, leg veins and complementary networks like the lymphatic system that have no pump to drive flow.

"With the addition of multivascular and intravascular structure, we're introducing an extensive set of design freedoms for engineering living tissue," Miller said. "We now have the freedom to build many of the intricate structures found in the body."

Miller and Grigoryan are commercializing key aspects of the research through a Houston-based startup company called Volumetric. The company, which Grigoryan has joined full time, is designing and manufacturing bioprinters and bioinks.

Miller, a longstanding champion of open-source 3D printing, said all source data from the experiments in the published Science study are freely available. In addition, all 3D printable files needed to build the stereolithography printing apparatus are available, as are the design files for printing each of the hydrogels used in the study.

"Making the hydrogel design files available will allow others to explore our efforts here, even if they utilize some future 3D printing technology that doesn't exist today," Miller said.

Miller said his lab is already using the new design and bioprinting techniques to explore even more complex structures.

"We are only at the beginning of our exploration of the architectures found in the human body," he said. "We still have so much more to learn."

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Scientists print first 3D heart using patient's biological materials

A 3D-printed, small-scaled human heart engineered from the patient's own materials and cells.

In a major medical breakthrough, Tel Aviv University researchers have "printed" the world's first 3D vascularised engineered heart using a patient's own cells and biological materials. Their findings were published on April 15 in a study in Advanced Science.

Until now, scientists in regenerative medicine -- a field positioned at the crossroads of biology and technology -- have been successful in printing only simple tissues without blood vessels.

"This is the first time anyone anywhere has successfully engineered and printed an entire heart replete with cells, blood vessels, ventricles and chambers," says Prof. Tal Dvir of TAU's School of Molecular Cell Biology and Biotechnology, Department of Materials Science and Engineering, Center for Nanoscience and Nanotechnology and Sagol Center for Regenerative Biotechnology, who led the research for the study.

Heart disease is the leading cause of death among both men and women in the United States. Heart transplantation is currently the only treatment available to patients with end-stage heart failure. Given the dire shortage of heart donors, the need to develop new approaches to regenerate the diseased heart is urgent.

"This heart is made from human cells and patient-specific biological materials. In our process these materials serve as the bioinks, substances made of sugars and proteins that can be used for 3D printing of complex tissue models," Prof. Dvir says. "People have managed to 3D-print the structure of a heart in the past, but not with cells or with blood vessels. Our results demonstrate the potential of our approach for engineering personalized tissue and organ replacement in the future."

Research for the study was conducted jointly by Prof. Dvir, Dr. Assaf Shapira of TAU's Faculty of Life Sciences and Nadav Moor, a doctoral student in Prof. Dvir's lab.

"At this stage, our 3D heart is small, the size of a rabbit's heart," explains Prof. Dvir. "But larger human hearts require the same technology."

For the research, a biopsy of fatty tissue was taken from patients. The cellular and a-cellular materials of the tissue were then separated. While the cells were reprogrammed to become pluripotent stem cells, the extracellular matrix (ECM), a three-dimensional network of extracellular macromolecules such as collagen and glycoproteins, were processed into a personalized hydrogel that served as the printing "ink."

After being mixed with the hydrogel, the cells were efficiently differentiated to cardiac or endothelial cells to create patient-specific, immune-compatible cardiac patches with blood vessels and, subsequently, an entire heart.

According to Prof. Dvir, the use of "native" patient-specific materials is crucial to successfully engineering tissues and organs.

"The biocompatibility of engineered materials is crucial to eliminating the risk of implant rejection, which jeopardizes the success of such treatments," Prof. Dvir says. "Ideally, the biomaterial should possess the same biochemical, mechanical and topographical properties of the patient's own tissues. Here, we can report a simple approach to 3D-printed thick, vascularized and perfusable cardiac tissues that completely match the immunological, cellular, biochemical and anatomical properties of the patient."

The researchers are now planning on culturing the printed hearts in the lab and "teaching them to behave" like hearts, Prof. Dvir says. They then plan to transplant the 3D-printed heart in animal models.

"We need to develop the printed heart further," he concludes. "The cells need to form a pumping ability; they can currently contract, but we need them to work together. Our hope is that we will succeed and prove our method's efficacy and usefulness.

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3D printing 100 times faster with light

Rather than building up plastic filaments layer by layer, a new approach to 3D printing lifts complex shapes from a vat of liquid at up to 100 times faster than conventional 3D printing processes, University of Michigan researchers have shown.

3D printing could change the game for relatively small manufacturing jobs, producing fewer than 10,000 identical items, because it would mean that the objects could be made without the need for a mold costing upwards of $10,000. But the most familiar form of 3D printing, which is sort of like building 3D objects with a series of 1D lines, hasn't been able to fill that gap on typical production timescales of a week or two.

"Using conventional approaches, that's not really attainable unless you have hundreds of machines," said Timothy Scott, U-M associate professor of chemical engineering who co-led the development of the new 3D printing approach with Mark Burns, the T.C. Chang Professor of Engineering at U-M.

Their method solidifies the liquid resin using two lights to control where the resin hardens -- and where it stays fluid. This enables the team to solidify the resin in more sophisticated patterns. They can make a 3D bas-relief in a single shot rather than in a series of 1D lines or 2D cross-sections. Their printing demonstrations include a lattice, a toy boat and a block M.

"It's one of the first true 3D printers ever made," said Burns, professor of chemical engineering and biomedical engineering.

But the true 3D approach is no mere stunt -- it was necessary to overcome the limitations of earlier vat-printing efforts. Namely, the resin tends to solidify on the window that the light shines through, stopping the print job just as it gets started.

By creating a relatively large region where no solidification occurs, thicker resins -- potentially with strengthening powder additives -- can be used to produce more durable objects. The method also bests the structural integrity of filament 3D printing, as those objects have weak points at the interfaces between layers.

"You can get much tougher, much more wear-resistant materials," Scott said.

An earlier solution to the solidification-on-window problem was a window that lets oxygen through. The oxygen penetrates into the resin and halts the solidification near the window, leaving a film of fluid that will allow the newly printed surface to be pulled away.

But because this gap is only about as thick as a piece of transparent tape, the resin must be very runny to flow fast enough into the tiny gap between the newly solidified object and the window as the part is pulled up. This has limited vat printing to small, customized products that will be treated relatively gently, such as dental devices and shoe insoles.

By replacing the oxygen with a second light to halt solidification, the Michigan team can produce a much larger gap between the object and the window -- millimeters thick -- allowing resin to flow in thousands of times faster.

The key to success is the chemistry of the resin. In conventional systems, there is only one reaction. A photoactivator hardens the resin wherever light shines. In the Michigan system, there is also a photoinhibitor, which responds to a different wavelength of light.

Rather than merely controlling solidification in a 2D plane, as current vat-printing techniques do, the Michigan team can pattern the two kinds of light to harden the resin at essentially any 3D place near the illumination window.

U-M has filed three patent applications to protect the multiple inventive aspects of the approach, and Scott is preparing to launch a startup company.

Read more at Science Daily