Exclusive: 3D Printed Cardiac Patch Shows Promise for Healing Damaged Hearts

Hexagonal scaffolds induce iPSC-CM contractile properties and maturation. iPSC-CM characterization before combination with scaffold, showing A) proliferating cells, B) sarcomeric structures, C) Connexin 43 (Cx43), and D) mitochondrial localization. iPSC-CMs localize to both E) hexagonal and F) rectangular fiber scaffolds, and confocal microscopy shows G,H) Cx43 expression, and increased sarcomere density, I,J) alignment, and K) length in hexagonal scaffolds compared to rectangular scaffolds. L) Beating rate at days 2, 7, 10, 11, and 14. M) Cardiac marker and maturation-related gene expression in hexagonal and rectangular scaffolds at day 7 and day 14.

After a person suffers a heart attack, they lose about half the cells in their heart, greatly weakening the organ and increasing the odds that further attacks will occur. Doctors have begun injecting cells into the heart to grow into muscle and help contractions, but 99% of those cells get washed away. But there are alternative approaches – like 3D printing. Scientists have developed 3D printed cardiac patches that can be used to repair hearts damaged by heart attacks, but only about five have been produced worldwide.

Injectability and in vivo placement of cardiac patch with hexagonal geometry. A) In vitro culture of cardiac patch consisting of iPSC-CMs in cardiac-like ECM on large hexagonal scaffolds. B) In vitro injectability, shape recovery, and C) macro image of cardiac patch after injection. D) Application and shape recovery of cardiac patch on beating porcine heart. E) Cell viability of in vitro F,G) noninjected and H,I) injected cardiac patches. J) Spontaneous beating rate of in vitro noninjected and injected cardiac patches 30 min and 2 d after injection.

In a new study entitled “Melt Electrowriting Allows Tailored Microstructural and Mechanical Design of Scaffolds to Advance Functional Human Myocardial Tissue Formation,” a group of researchers 3D printed a world-first stretchable microfiber scaffold with a hexagonal design. They then added specialized stem cells called iPS-Cardiomyocytes, which began to contract unstimulated on the scaffold. The work was then demonstrated on the actual hearts of pigs.

We spoke with the authors of the paper to learn more about the technology used by the scientists and its implications for the future.

What are the advantages of MEW relative to other technologies? 

“Melt Electrospin Writing (MEW) has distinct advantages over other 3D Printing technologies for tissue engineering applications. MEW utilises common thermoplastics used in biomedical engineering, including Polycaprolactone (PCL). The advantage of this approach is that we are able to create microfibres with diameters often in the 10 micron range, but nano-fibres also also achievable. To put this into perspective, a single strand of hair is about 50-100 microns. Printing at such resolutions allows us to mimic the native extracellular matrix (ECM) components, and allows cells to bind onto the small fibres that at similar to collagen fibrils. Additionally, MEW allows for the control over scaffold architecture, creating scaffolds with aligned fibres and controlled fibre diameters. This specific control over architecture, allows us to tailor the mechanical properties, direct cells growth and  control the movement of nutrients. Because we can modify the scaffolds properties so well, they are often used to reinforce hydrogels (as a backbone), which are typically much weaker and less tailorable.”

What is the significance of your paper?

Representation of the workflow and fabricated microfiber scaffolds. A) Schematic illustration of the in house-built MEW device used. B) Designed hexagonal microstructure. C) 3D fiber scaffold combined with iPSC-CMs and further application in vivo through minimally invasive delivery. D) Optical images of the fabricated scaffolds: detail of microstructure with hexagonal cells (with a side length of 400 µm) composed of multiple stacked aligned microfibers. Images acquired from top and lateral perspective.

“We developed patches with controlled hexagonal micro-fibre structures that had unique flexibility and shape-recovery properties, meaning that the patch can be highly deformed without sustaining damage to its structure or cells. Moreover, such novel paths allowed the maturation of contractile human iPSC-derived cardiomyocytes, which is a breakthrough in creating a functional patch that could match an adult heart. Finally, due to the patch’s flexibility, it can be compressed and pushed through a catheter for delivery in vivo with minimally invasive laparoscopic surgery.”

Why are collagen-based hydrogels so important?

“Collagen is the most abundant protein in the human myocardial tissue and for that reason an ideal biomaterial for use in myocardial tissue engineering.”

How close are we to using 3D printing in a clinical setting?

“There are already reports of 3D printed implants used in clinics, mostly metallic or ceramic based for bone repair. However, in what concerns to our heart patch’s that include biological derived components (new cell therapies, iPSC) we believe a few more years will be required. We need first to demonstrate the efficacy and safety of such approach in animal models, which we are currently planning. Also, important challenges like integration with surrounding tissue will need to be solved: for example, currently the patches can contract autonomously, but we don’t know if they will sync with the beating of the heart once implanted.”

What work will you be doing next?

“We want to concentrate our efforts in conducting more extensive animal studies to assess feasibility and show functional effects, such as improved cardiac function. We also intend to make the patches more complex, by integrating other cell types in the patch.”

Authors of the paper include Miguel Castilho, Alain van Mil, Malachy Maher, Corina H.G. Metz, Gernot Hochleitner, Jürgen Groll, Pieter A. Doevendans, Keita Ito, Joost P.G. Sluijter, and Jos Malda.

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[Images: Castilho et al, “Melt Electrowriting Allows Tailored Microstructural and Mechanical Design of Scaffolds to Advance Functional Human Myocardial Tissue Formation,” Advanced Functional Materials, 2018. Copyright Wiley – VCH Verlag GmbH & Co. KGaA. Reproduced with permission.]


3D Bioprinting: What Can it Do Right Now?

3D bioprinting is a hot term right now, but many people aren’t sure exactly what it’s all about. Bring up bioprinting to someone who is only marginally familiar with it, and their response is likely to be, “Oh, that’s where they’re trying to print organs and stuff, right?” Well…yes, that is one of the ultimate goals of bioprinting. Most people working in the space like to talk about the dream of eliminating donor waiting lists, and creating brand new organs from a patient’s own cells, greatly reducing the risk of rejection. But the day that we see a beating 3D printed heart implanted into the chest of a living human being is still several years away.

Organ transplants are not the be-all, end-all of 3D bioprinting, however. Many people, unless they’re familiar with the industry, are unaware of just how much is being done with the technology already, and how many people are being helped by it, either directly or indirectly. Here are just some of the ways in which bioprinting is already impacting people.

Pharmaceutical Testing

[Image: Organovo]

There are many reasons why new drugs take so long to get approved for the market. One of them is that testing drugs on animal tissue is different from testing it on human tissue. A drug can work perfectly on an animal, but fail on a human – it’s inevitable that that should happen sometimes, as our systems process things differently than those of mice. But companies such as Organovo have developed 3D bioprinted human kidney and liver tissue – and yes, Organovo ultimately wants to be able to transplant working 3D printed livers into humans, but in the meantime, the company has made tremendous strides using its 3D printed tissue for pharmaceutical testing.

Testing drugs on actual human tissue can give researchers a real idea of how the drugs will react in a human system, whether they’ll be effective and if they’ll cause any sort of harmful effects. 3D printed tissue also eliminates the need for testing on animals at all, which is a bonus for those animals.

3D Printed Cartilage and Bone

[Image: St. Vincent’s Hospital

Much research has gone into the 3D printing of 3D printed bone and cartilage. Last year, Australian researchers successfully transplanted 3D printed knee cartilage into sheep, paving the way for human trials and commercialization. While it’s not yet possible to 3D print a functioning organ for human transplant, great progress has been made in treating diseases like arthritis by 3D printing new cartilage. Using a patient’s own stem cells, scientists hope to be able to 3D print pieces of cartilage and transplant them into a diseased or injured joint, where they will integrate with the body, grow and ultimately heal the affected area. This hasn’t actually been done to a human yet, but applications like this are much closer over the horizon than, say, a 3D printed heart.

3D printed bone is also being studied as a way to replace bone that has been lost due to injury or illness. Severe conditions resulting in the loss of bone, if they can be treated at all, are typically treated with bone grafts, which can cause complications or rejection, and may be impossible simply because the patient doesn’t possess enough bone to heal a particular defect. 3D printed bone, again, can be created from a patient’s own cells, making it far less likely to be rejected. It can be 3D printed in any shape or size to match the defect and integrate with existing bone to heal it.

3D Printed Patches

Perhaps we can’t implant a 3D printed organ yet, but work has been done toward 3D printed patches to repair damaged organs, such as hearts after a heart attack. Progress has been made toward getting these 3D printed cell patches to vascularize, meaning that they can form their own blood vessel networks and survive inside the body.

Disease Research

Some diseases are difficult to study because of the lack of access to the affected area, such as the placenta. But a bioprinted placenta allowed scientists to research the dangerous condition preeclampsia more thoroughly than ever before and even come up with potential treatments. As bioprinting progresses, 3D printed organs will lead to better research and treatments even before they can be implanted into humans.

3D Printed Organs

Yes, it may be a long time before organs can be 3D printed and implanted into humans – but they have been, in a few cases, successfully transplanted into animals. A mouse with a 3D printed ovary successfully gave birth to multiple babies, and before that 3D printed thyroid glands were transplanted into mice. Again, there’s a long way between mice and humans, but these cases show that 3D printed organs are a possibility and that they could perhaps be made to function inside the body. In each case, the researchers made known their intentions to eventually transfer this technology to humans. 3D printed, transplantable human organs are likely going to be part of the future – it’s just a matter of when.

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3D Printing and Electrospinning PCL for Dressings and Wound Repair

When the body is functioning as it should, wounds repair themselves naturally. Sometimes, however, wounds do not heal, due to conditions such as diabetes or other chronic diseases. This puts the patient at risk of infection and other complications, at worst even requiring amputation. Chronic wounds affect 37 million patients around the world, and there is a great need for better treatment of these wounds.

In her Master’s Degree thesis, Politecnico di Torino student Viola Sgarminato discusses how 3D bioprinting and electrospinning can create scaffolds that actually promote wound repair. Using a combination of electrospinning and 3D printing with an EnvisionTEC 3D-Bioplotter, Sgarminato developed scaffolds that would promote healing by electrically stimulating skin cells.

“To this aim hierarchical scaffolds of polycaprolactone (PCL) and piezoelectric barium titanate (BaTiO3) nanoparticles were fabricated using 3D-bioprinting and the electrospinning technique,” Sgarminato explains.

Electrospinning is a technique that has been used for decades, and it involves the use of an electric charge to spin nanometer threads from a polymer solution. Lately, it’s been frequently used in conjunction with 3D printing, particularly bioprinting. In one part of the study, Sgarminato used the technique to create fibrous patches. She also used a 3D-Bioplotter to 3D print scaffolds for skin regeneration.

“In this work the bio-plotting technique was used to produce polycaprolactone (PCL) scaffolds with and without barium titanate nanoparticles,” she says. “Several sample thicknesses, porosities and geometries were tested to obtain optimized scaffolds for skin regeneration. Low and high temperature processes were performed to produce piezoelectric and nonpiezoelectric scaffolds, respectively. Indeed, to print scaffolds with homogenously distributed BTNPs, a solution of PCL and consequently a low temperature process are needed.”

The scaffolds were seeded with cells, which were then evaluated 24 and 72 hours later.

For the electrospinning portion of the project, one solution, in particular, worked better at producing defect-free mats of fibers – PCL was the key ingredient. The 3D printed scaffolds were examined to test their porosity, and to compare those that were produced through high temperature and low-temperature 3D printing. The composite wound dressings were also examined using a scanning electron microscope to verify the adhesion of the fibers to the scaffold, and good results were shown: even if subjected to mechanical stretching, the fibers remained attached to the substrate.

SEM images of electrospun fibers deposited onto a composite scaffold.

“The results that have been measured in 3T3 cells after 24h from seeding demonstrate that the cellular adhesion is comparable for each substrate,” says Sgarminato. “By considering the absorbance values after 72h, the highest increment of proliferation occurs for samples 4,5 and 6 that correspond to the PCL nanofibers…Indeed, PCL electrospun nanofibers represent a suitable substrate for growth and proliferation of NIH 3T3 cells. The small differences between PCL nanofibers and composites (samples 7 and 8) suggest a good cytocompatibility of the composite wound dressings. On the contrary, as expected, the printed scaffolds without nanofibers (samples 2 and 3) are not appropriate substrates for cell proliferation because of the limited culture surface.”

You can read the full thesis, entitled “Composite scaffolds with porosity over multiple length scale for skin regeneration,” here. The paper demonstrates that electrospinning and 3D bioprinting are effective methods of creating wound dressings that can treat chronic wounds and promote healing. This is an important application of bioprinting; while many people excitedly await the day that it’s possible to 3D print and transplant working human organs, it’s applications like these that are more immediate and can save lives just as effectively as a new heart.

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Printing Lungs Using 3D, Bioprinting, and Stem Cells

via MIT Technology Review

Last month I had the chance to hold a replica of the upper part of a human airway—the windpipe plus the first two bronchi. It had been made from collagen, the biological cement that holds our bodies together. It was slippery and hollow, with the consistency of undercooked pasta.

The structure had emerged from a refrigerator-size 3-D printer in Manchester, New Hampshire, at an outpost of United Therapeutics, a company that earns more than a billion dollars a year selling drugs to treat lung ailments.

One day, the company says, it plans to use a printer like this one to manufacture human lungs in “unlimited quantities” and overcome the severe shortage of donor organs.

Bioprinting tissue isn’t a new idea. 3-D printers can make human skin, even retinas. Yet the method, so far, has been limited to tissues that are very small or very thin and lack blood vessels.

United instead is developing a printer that it believes will be able, within a few years, to manufacture a solid, rubbery outline of a lung in exquisite detail, including all 23 descending branches of the airway, the gas-exchanging alveoli, and a delicate network of capillaries.

A lung made from collagen won’t help anyone: it’s to a real lung what a rubber chicken is to an actual hen. So United is also developing ways to impregnate the matrix with human cells so they’ll attach and burrow into it, bringing it alive.

“We are trying to build the little stick houses for cells to live in,” says Derek Morris, a project leader in United’s organ manufacturing group.

Read more!

Student Uses 3D Printing to Develop Vocal Prosthetic

Nikita Dubrovsky

Cancer of the larynx is treatable, but it sometimes requires removing the larynx altogether, leaving the patient unable to speak. There are, however, vocal prostheses that can be implanted to restore the patient’s speech. Unfortunately, these prostheses are expensive and tend to need frequent replacement. So South Ural State University student Nikita Dubrovsky is working on an alternative.

“Everywhere in the world, the method being chosen for vocal rehabilitation of the patients who underwent laryngectomy is the voice prosthetic care,” said Dubrovsky. “Most often abroad-manufactured apparatus are used which allow patients to recover their voice. But the big minus here is that such an apparatus is due for replacement after approximately just one year. Imported prostheses are quite expensive, so we decided to come up with our own development, which will feature similar technical characteristics, but will be much cheaper.”

Vocal prostheses first began being used in 1980. A shunt is placed between the trachea and upper esophagus, and a valve is implanted into the opening. This valve allows for the exhalation of air from the trachea to the esophagus, which creates vibration in the walls of the esophagus and the lower pharynx, generating sound. These valves have more than one drawback, however.

“The abroad-manufactured prostheses mostly use plastic, which is very inconvenient because it’s hard,” explained Dubrovsky. “We’re planning on using food silicones, which will make the prosthesis softer, and patients will less suffer from pain. The forms for drip moulding, which we will be filling with silicone, will be manufactured using 3D printing.”

A 3D model of the vocal prosthetic was created, and scientists at the SUSU Research Center for Sport Science have used SLA 3D printing to create a prototype, which will be sent for clinical testing at the Chelyabinsk Regional Center for Oncology and Nuclear Medicine.

“Unfortunately, when we were working with 3D printing, we faced damages that occurred in the drip-moulding tank in the process of the model creation,” said Dubrovsky. “Moreover, such process of production may take 12 to 24 hours, which is a very long time. Since 3D printing turned to be not that accurate, we will probably have to give it up in the future and turn to lathe operators instead, as they are in command of high-accuracy equipment. But first we need to improve our computer model.”

Dubrovsky and his fellow researchers will continue work on the implant as Dubrovsky continues work towards his Master’s degree; he just graduated with a Bachelor’s in Physical Education. They will work on finding food-grade silicone of optimum hardness for patient comfort.

Dubrovsky’s work is potentially good news for the future of patients who require larynx removal; unfortunately, this week also brings some bad news for Italian surgeon Paolo Macchiarini and his patients. Macchiarini published a paper in 2011 in the medical journal The Lancet regarding an artificial windpipe he had created that was coated with the patient’s own stem cells, which would then develop into mature tracheal cells that would not be rejected by the patient’s body. It sounds like a groundbreaking development in bioprinting, but it turns out that the procedure was worse than ineffective.

Macchiarini and colleagues performed the procedure on a total of eight patients, seven of whom died. The surgeons lost track of the eighth. Macchiarini was associated with the Karolinska Institute, which awards the Nobel Prize in medicine every year. In 2014, several surgeons at Karolinska filed a complaint alleging that Macchiarini had downplayed the risks of the procedure, and that it had been carried out on at least one patient who had not been critically ill at the time.

Paolo Macchiarini [Image: Lorenzo Galassi/AP]

Recently, the new President of the Karolinska Institute, Ole Petter Ottersen, requested that The Lancet retract two papers published by Macchiarini, and the journal obliged, as explained in a recent editorialThe Lancet is a prestigious medical journal that only publishes work after extensive peer review, so such a retraction is extremely rare.

“No ethical permit had been obtained for the underlying research,” said Ottersen. “The research was carried out without sufficient support by preclinical data, and the paper presents its data in a way that is unduly positive and uncritical. The clinical findings reported are not supported by source data.”

Macchiarini and his co-authors were found guilty of misconduct, and two members of the Nobel medicine prize assembly were forced to step down.

Discuss these and other 3D printing topics at 3DPrintBoard.com or share your thoughts below. 

[Sources: South Ural State University, CTV News / Images: Viktoria Matveichuk unless otherwise noted]


Indiana University and Lung Biotechnology Partner to Advance 3D Printing of Organs

One of the reasons why I really enjoy writing about 3D printing is because it is a fabulous mix of the fun and the important. The stories we cover can be anything from the enjoyable experience of standing before a giant 3D printed skeleton to the very serious nature of fabricating necessary objects on a 3D printer onboard the International Space Station. The work done by these machines and the people that operate them has, time and again, proven to offer a helping hand (sometimes literally as in the case of prosthetics) to boosting the quality of life of a growing number of individuals.

From left to right: Lester Smith, PhD, Burcin Ekser, MD, PhD and Ping Li, PhD [Image:Eric Schoch, IUSM]

One area in which 3D printing is making particularly important contributions is in the field of medicine. Over the past several years, we have seen stories about students getting hands-on experience through 3D printed models and of improved patient outcomes as a result of preparation and the fabrication of custom surgical equipment for the medical team. With the introduction of bioprinting, the ultimate dream in medicine has been to advance to the point of being able to 3D print whole organs that could be used to replace those that are failing in patients. Thus far, that is still a dream for the future, but important advances are being made in that direction, sometimes great strides, other times only baby steps.

One of the most recent steps forward has come in the form of an agreement between faculty at Indiana University (IU) School of Medicine and the Maryland-based company Lung Biotechnology PBC, that is focused on organ transplantation technologies. The hope is that the $9 million project will result in the knowledge necessary to make the dream of 3D printing organs into a reality. They won’t be starting from scratch; the IU team is already able to generate tissues, but they will use the funding provided through this partnership to analyze the tissues and their structures in order to possibly unlock the key to more advanced organ creation. Dr. Lester Smith, an Assistant Professor of Radiology and Imaging Sciences at IU School of Medicine and the head of the research team, explained the prolonged nature of any such investigation:

“[I]f someone has a skin burn, maybe we can replace skin. Or if someone has a bad liver then we can replace the liver entirely. But this is way down the road. Most of our tissues which make up our organs have a lot of different cell types. They are also vascularized, which means they have a lot of blood vessels that are basically channeling through them. When we get there that’s when I can tell you how long it took. That’s because the body is so complex and there’re so many different parts and so many responses. I couldn’t tell you how long it would take but we’re on the road to that destination.”

Luckily, Indiana University and Lung Biotechnology don’t have to make all the headway by themselves; there are a large number of organizations, from large to small and public to private, pursuing the dream of fabricating organs. This is more than just an effort to do something to see if it can be done; there are people dying every year because they cannot get access to the organs that they need, and further deaths and astronomical medical expenses to deal with for those whose bodies strongly reject the foreign organs. Should it become possible to create a custom organ for someone using their own cells, the entire process from the surgery to simple day to day functionality would be vastly improved, and this partnership should help push that research closer to the gold standard.

What do you think of this news? Let us know your thoughts; join the discussion of this and other 3D printing topics at 3DPrintBoard.com or share your thoughts below.

[Source: Indiana Public Media]


Zero Gravity Bioprinter is Ready for Delivery to the International Space Station

An amazing thing happened two years ago, when Techshot and nScrypt worked together to 3D print a human heart – in zero gravity. Not a working heart, yet, but the two companies were the first to 3D print cardiac and vascular structures in zero gravity using adult human stem cells. Why would they do such a thing, you might ask? The reasoning is much more than “because they can,” as 3D bioprinting in zero gravity is actually easier and more effective than it is on Earth.

Earth-based bioprinting requires thick, viscous bioinks that can contain chemicals or other materials necessary for providing structural support. The lack of gravity in space, however, means that thinner, purer bioinks can be used, as well as thinner print nozzles, allowing for more precision and control. When the first viable human organ is 3D printed, it may very well happen in space.

After nScrypt and Techshot pulled off their successful zero-G bioprinting feat, they began work on the 3D BioFabrication Facility, or BFF, a 3D bioprinting system for the International Space Station. The BFF can 3D print thick tissue and organs using adult stem cells. The printing will happen on an nScrypt 3D Bio Assembly Tool, or BAT; the bioink will be printed into a specialized cell culturing bioreactor cassette designed by TechShot and conditioned in the TechShot ADvanced Space Experiment Processor (ADSEP). The BFF and ADSEP are scheduled to launch on their way to the ISS in February 2019.

The nScrypt BAT 3D printer features high-precision motion and extreme dispensing control, and will use nScrypt’s patented SmartPump, which has 100 picoliter volumetric control and uses super-fine nozzles, down to 10 microns, to dispense biomaterials. This enables the highly controlled and repeatable placement of bioink, which is necessary for printing the fine details of tissues and organs.

“Especially when dealing with something as important as tissue, it is vital to place the correct amount of material in the correct position every time,” said nScrypt CEO Ken Church. “This is what our machines offer and what has contributed to our success in bioprinting as well as other applications. This is an exciting time for discovery and more importantly a time of impact for those that are seriously seeking solutions to grow thick vascularized tissue, which is the basis for a fully printed organ.”

The first complete print, after the initial test prints, will be a cardiac patch for damaged hearts. Cells will be printed into the bioreactor cassette, and the bioreactor will then provide media perfusion to deliver nutrients and remove toxins from the tissue, keeping it alive while providing electrical and mechanical stimulus to encourage the cells to become beating heart tissue.

Rendering of the BFF in an EXPRESS rack [Image: nScrypt]

The BFF may truly be an astronaut’s BFF; in addition to 3D printing tissue for people on Earth, it can print pharmaceuticals and even food on demand for people on the International Space Station.

“We are very excited to see this project, and all that it can provide, come to life,” said Techshot President and CEO John C. Vellinger. “With the goal of producing everything from organs, to pharmaceuticals, to perhaps even food, the BFF has the ability to improve the lives of people on earth and help enable deep space exploration.”

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3D Printing with Magnets in Microgravity

While methods of 3D bioprinting vary, most of them have one thing in common – they print cells layer by layer into a desired shape, which is then transferred to an incubator where it further grows and develops. Alternative methods exist, however, that involve the manipulation of the cell material by magnetic fields. The cells are then “labeled” with magnetic nanoparticles. But now a Russian research team has developed a new method of bioprinting that neither prints layer by layer nor uses magnetic labeling. This method could lead to the creation of radiation-sensitive biological constructs and the repair of organs and tissues.

The new method, which involves magnetic levitation research in conditions of microgravity, was conducted by the 3D Bioprinting Solutions company in collaboration with other Russian and foreign scientists, including the Joint Institute for High Temperatures of the Russian Academy of Sciences (JIHT RAS).

“During the period from 2010 to 2017, a series of experimental studies were carried out aboard the Russian Orbital Segment of the International Space Station with the Coulomb Crystal experimental device,” said Mikhail Vasiliev, head of the laboratory of dusty plasma diagnostics in JIHT RAS. “The main element of the device is an electromagnet that creates a special inhomogeneous magnetic field in which the structures of the diamagnetic particles (they are magnetized against the direction of the magnetic field) can be formed in the microgravity conditions.”

The research was documented in a paper entitled “Scaffold-free, label-free and nozzle-free biofabrication technology using magnetic levitational assembly,” which you can access here. In the study, the researchers describe how small charged particles behave in the magnetic field of a special shape under microgravity or zero-gravity conditions. They also developed a mathematical model of this process based on the methods of molecular dynamics. These results explain how to obtain homogeneous and extended three-dimensional structures consisting of thousands of the particles.

Conventional methods of magnetic 3D bioprinting had several limitations associated with gravity. There are a couple of ways to reduce the power of gravitational forces, one being to increase the power of the magnets that control the magnetic field. This will, however, require a much more complex bioprinter. Another way is to reduce the gravity, which is the approach used by the scientists from 3D Bioprinting Solutions. The method is called formative three-dimensional biofactory, which creates three-dimensional biological structures immediately from all sides, rather than in layers.

The researchers applied the experimental data and the results of the mathematical modeling obtained by the JIHT RAS scientists in order to control the shape of the structures.

“The results of the Coulomb crystal experiment on the study of the formation of the spatially ordered structures led to the development of a new method for the formative 3-D biofactory of the tissue-like structures based on the programmable self-assembly of the living tissues and organs under the conditions of gravity and microgravity by means of an inhomogeneous magnetic field,” said Vasiliev.

Bioprinters based on this new technology will be able to create biological constructs that can be used for many purposes, including estimating the adverse effects of space radiation on the health of astronauts on long-term space missions. It should also be able to restore the function of damaged tissues and organs.

Authors of the paper include Vladislav A. Parfenov, Elizaveta V. Koudan, Elena A. Bulanova, Pavel A. Karelkin, Frederico DAS Pereira, Nikita E. Norkin, Alisa D. Knyazeva, Anna A. Gryadunova, Oleg F. Petrov, Mikhail M. Vasiliev, Maxim I. Myasnikov, Valery P. Chernikov, Vladimir A. Kasyanov, Artem Yu Marchenkov, Kenn Brakke, Yusef D. Khesuani, Utkan Demirci, and Vladimir A. Mironov.

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[Source: Phys.org]


Researchers 3D Print Tissue That Mimics Human Bile Duct

[Image via Cancer.org]

A bile duct plays a crucial role in the body, carrying bile from the liver to the intestine to facilitate digestion. Cancer of the bile duct has an alarmingly low survival rate, and treatment requires that the disease be caught early enough for the affected part of the bile duct to be removed. But there’s some good news for those suffering from conditions of the bile duct, as researchers at Northwestern University have 3D printed a mini-tissue that mimics it.

The research is documented in a study entitled “Tailoring nanostructure and bioactivity of 3D-printable hydrogels with self-assemble peptides amphiphile (PA) for promoting bile duct formation,” which you can access here. Lead author Ming Yan and colleagues 3D printed a nanostructure consisting of peptides amphiphile, or PAs, bioink and bile duct cells, or cholangiocytes.

“3D-printing has expanded our ability to produce reproducible and more complex scaffold architectures for tissue engineering applications,” the abstract states. “In order to enhance the biological response within these 3D-printed scaffolds incorporating nanostructural features and/or specific biological signaling may be an effective means to optimize tissue regeneration. Peptides amphiphiles (PAs) are a versatile supramolecular biomaterial with tailorable nanostructural and biochemical features. PAs are widely used in tissue engineering applications such as angiogenesis, neurogenesis, and bone regeneration. Thus, the addition of PAs is a potential solution that can greatly expand the utility of 3D bioprinting hydrogels in the field of regenerative medicine.”

The PAs and cholangiocytes were mixed with thiolated gelatin at 37°C and 3D printed at 4ºC using an EnvisionTEC 3D-Bioplotter, one of the most-utilized bioprinters on the market. The material retained integrity as the bioinks printed into filaments capable of supporting multi-layered scaffolds. The researchers stabilized the scaffold by cross-linking a derivative of ethylene glycol with calcium ions; scaffold stability was observed in culture for more than a month at a temperature of 37°C.

First author Ming Yan. [Image: Northwestern via Physics World]

The researchers also explored the use of a laminin-derived peptide (Ile-Lys-Val-Ala-Val, IKVAV) and the influence its inclusion in the bioink would have on the bile duct cells. Laminin is a molecule necessary for cell adhesion, and after bioprinting, the bile duct cells remained viable in vitro. Staining revealed the formation of functional bile-cell-based tube structures; when cultured in IKVAV bioink, the structures showed enhanced morphology, forming functional tubular structures.

This is the first time that a bioink-based system supplemented with PAs was used for bile duct tissue engineering. The research shows a lot of promise; the bioprinted bile ducts as well as in vitro systems created with the bioinks have the potential to be valuable for research into bile duct cancer as well as the testing of treatments. Right now, bile duct cancer is a grave diagnosis to receive, but the enhanced research that could be made possible by this work offers hope for better understanding and more effective treatments.

As a next step, the researchers now want to optimize the peptide concentration and test other signaling molecules within the bioinks to enhance the formation of functional tubular structures that mimic those found in the liver.

Additional authors of the research paper include P.L. Lewis and R.N. Shah.

[Source: Physics World]