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Scientists at the University of Oxford have developed a radical new method of 3D-printing laboratory-grown cells that can form complex living tissues and cartilage to potentially support, repair, or augment diseased and damaged areas of the body. Printing high-resolution living tissues is currently difficult because the cells often move within printed structures and can collapse on themselves. So the team devised a new way to produce tissues in protective nanoliter droplets wrapped in a lipid (oil-compatible) coating that is assembled, layer-by-layer, into living cellular structures. This new method improves the survival rate of the individual cells and allows for building each tissue one drop at a time to mimic the behaviors and functions of the human body. The patterned cellular constructs, once fully grown, can mimic or potentially enhance natural tissues. “We were aiming to fabricate three-dimensional living tissues that could display the basic behaviors and physiology found in natural organisms,” explained Alexander Graham, PhD, lead author and 3D Bioprinting Scientist at OxSyBio (Oxford Synthetic Biology). “To date, there are limited examples of printed tissues [that] have the complex cellular architecture of native tissues. Hence, we focused on designing a high-resolution cell printing platform, from relatively inexpensive components, that could be used to reproducibly produce artificial tissues with appropriate complexity from a range of cells, including stem cells.” The researchers hope that with further development, the materials could have a wide impact on healthcare worldwide and bypass clinical animal testing. The scientists plan to develop new complementary printing techniques that allow for a wider range of living and hybrid materials, producing tissues at industrial scale.
By Gabe Cherry
In research that could one day lead to advances against neurodegenerative diseases like Alzheimer's and Parkinson's, University of Michigan engineering researchers have demonstrated a technique for precisely measuring the properties of individual protein molecules floating in a liquid.
Proteins are essential to the function of every cell. Measuring their properties in blood and other body fluids could unlock valuable information, as the molecules are a vital building block in the body. The body manufactures them in a variety of complex shapes that can transmit messages between cells, carry oxygen and perform other important functions.
Sometimes, however, proteins don't form properly. Scientists believe that some types of these misshapen proteins, called amyloids, can clump together into masses in the brain. The sticky tangles block normal cell function, leading to brain cell degeneration and disease.
But the processes of how amyloids form and clump together are not well understood. This is due in part to the fact that there's currently not a good way to study them. Researchers say current methods are expensive, time-consuming and difficult to interpret, and can only provide a broad picture of the overall level of amyloids in a patient's system.
The University of Michigan and University of Fribourg researchers who developed the new technique believe that it could help solve the problem by measuring an individual molecule's shape, volume, electrical charge, rotation speed and propensity for binding to other molecules.
They call this information a "5-D fingerprint" and believe that it could uncover new information that may one day help doctors track the status of patients with neurodegenerative diseases and possibly even develop new treatments. Their work is detailed in a paper published in Nature Nanotechnology.
"Imagine the challenge of identifying a specific person based only on their height and weight," said David Sept, a U-M biomedical engineering professor who worked on the project. "That's essentially the challenge we face with current techniques. Imagine how much easier it would be with additional descriptors like gender, hair color and clothing. That's the kind of new information 5-D fingerprinting provides, making it much easier to identify specific proteins."
Michael Mayer, the lead author on the study and a former U-M researcher who's now a biophysics professor at Switzerland's Adolphe Merkle Institute, says identifying individual proteins could help doctors keep better tabs on the status of a patient's disease, and it could also help researchers gain a better understanding of exactly how amyloid proteins are involved with neurodegenerative disease.
To take the detailed measurements, the research team uses a nanopore 10-30 nanometers wide—so small that only one protein molecule can fit through at a time. The researchers filled the nanopore with a salt solution and passed an electric current through the solution.
As a protein molecule tumbles through the nanopore, its movement causes tiny, measurable fluctuations in the electric current. By carefully measuring this current, the researchers can determine the protein's unique five-dimensional signature and identify it nearly instantaneously.
"Amyloid molecules not only vary widely in size, but they tend to clump together into masses that are even more difficult to study," Mayer said. "Because it can analyze each particle one by one, this new method gives us a much better window to how amyloids behave inside the body."
Ultimately, the team aims to develop a device that doctors and researchers could use to quickly measure proteins in a sample of blood or other body fluid. This goal is likely several years off; in the meantime, they are working to improve the technique's accuracy, honing it in order to get a better approximation of each protein's shape. They believe that in the future, the technology could also be useful for measuring proteins associated with heart disease and in a variety of other applications as well.
"I think the possibilities are pretty vast," Sept said. "Antibodies, larger hormones, perhaps pathogens could all be detected. Synthetic nanoparticles could also be easily characterized to see how uniform they are."
The study is titled "Real-time shape approximation and fingerprinting of single proteins using a nanopore."
Nanoengineers at the University of California, San Diego have developed a 3D-printed device inspired by the liver to remove dangerous toxins from the blood. The device, which is designed to be used outside the body — much like dialysis — uses nanoparticles to trap pore-forming toxins that can damage cellular membranes and are a key factor in illnesses that result from animal bites and stings, and bacterial infections. The findings were published May 8 in the journal Nature Communications.
Nanoparticles have already been shown to be effective atneutralizing pore-forming toxins in the blood, but if those nanoparticles cannot be effectively digested, they can accumulate in the liver creating a risk of secondary poisoning, especially among patients who are already at risk of liver failure.
To solve this problem, a research team led by nanoengineering professor Shaochen Chen created a 3D-printed hydrogel matrix to house nanoparticles, forming a device that mimics the function of the liver by sensing, attracting and capturing toxins routed from the blood.
The device, which is in the proof-of-concept stage, mimics the structure of the liver but has a larger surface area designed to efficiently attract and trap toxins within the device. In an in vitro (lab) study, the device completely neutralized pore-forming toxins.
“One unique feature of this device is that it turns red when the toxins are captured,” said the co-first author, Xin Qu, who is a postdoctoral researcher working in Chen’s laboratory. “The concept of using 3D printing to encapsulate functional nanoparticles in a biocompatible hydrogel is novel,” said Chen. “This will inspire many new designs for detoxification techniques since 3D printing allows user-specific or site-specific manufacturing of highly functional products,” Chen said.
Chen’s lab has already demonstrated the ability to print complex 3D microstructures, such as blood vessels, in mere seconds out of soft biocompatible hydrogels that contain living cells.
As previously reported, Chen’s biofabrication technology, called dynamic optical projection stereolithography (DOPsL), can produce the micro- and nanoscale resolution required to print tissues that mimic nature’s fine-grained details, including blood vessels, which are essential for distributing nutrients and oxygen throughout the body.
Researchers are hopeful that new advances in tissue engineering and regenerative medicine could one day make a replacement liver from a patient’s own cells, or animal muscle tissue that could be cut into steaks without ever being inside a cow. Bioengineers can already make 2D structures out of many kinds of tissue, but one of the major roadblocks to making the jump to 3D is keeping the cells within large structures from suffocating; organs have complicated 3D blood vessel networks that are still impossible to recreate in the laboratory. Now, University of Pennsylvania researchers have developed an innovative solution to this perfusion problem: they’ve shown that 3D printed templates of filament networks can be used to rapidly create vasculature and improve the function of engineered living tissues.
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Fans of 3D printing say it has the potential to revolutionize medicine—think 3D-printed skin,ears, bone scaffolds, and heart valves. Now, prosthetic ovaries made of gelatin have allowed mice to conceive and give birth to healthy offspring. Such engineered ovaries could one day be used to help restore fertility in cancer survivors rendered sterile by radiation or chemotherapy. This “landmark study” is a “significant advance in the application of bioengineering to reproductive tissues,” says Mary Zelinski, a reproductive scientist at the Oregon National Primate Research Center in Beaverton who was not involved with the work. The researchers used a 3D printer with a nozzle that fired gelatin, derived from the collagen that’s naturally found in animal ovaries. The scientists built the ovaries by printing various patterns of overlapping gelatin filaments on glass slides—like building with Lincoln Logs, but on a miniature scale: Each scaffold measured just 15 by 15 millimeters. The team then carefully inserted mouse follicles—spherical structures containing a growing egg surrounded by hormone-producing cells—into these “scaffolds.” The scaffolds that were more tightly woven hosted a higher fraction of surviving follicles after 8 days, an effect the team attributes to the follicles having better physical support. The researchers then tested the more tightly woven scaffolds in live mice. The researchers punched out 2-millimeter circles through the scaffolds and implanted 40–50 follicles into each one, creating a “bioprosthetic” ovary. They then surgically removed the ovaries from seven mice and sutured the prosthetic ovaries in their place. The team showed that blood vessels from each mouse infiltrated the scaffolds. This vascularization is critical because it provides oxygen and nutrients to the follicles and allows hormones produced by the follicles to circulate in the blood stream. The researchers allowed the mice to mate, and three of the females gave birth to healthy litters, the team reports today in Nature Communications. The mice that gave birth also lactated naturally, which demonstrated that the follicles embedded in the scaffolds produced normal levels of hormones.
Via THE OFFICIAL ANDREASCY
With 3D printers everywhere, making everything from Yoda statues to bionic body parts, this company is using 3D printing to make new body tissue. BioBots, a team from the University of Pennsylvania, does just that. They’ve developed a $5,000 3D printer that actually prints functional living tissue. The company just snagged the Most Innovative Company at SXSW’s Accelerator Awards.
And while most of the living tissue BioBots is creating these days is for drug research — to make it less expensive and take animals out of the mix — one day, it could print new organs for transplants. “If we could somehow reveal the failures before testing drugs on people, we would be able to identify false positives much earlier in the drug development process,” CEO and co-founder Danny Cabrera told Forbes. “The problem is in animal testing – mice are not humans, and tests on animals often fail to mimic human diseases or predict how the human body responds to new drugs.
“The Holy Grail is to develop fully functioning replacement organs out of a patient’s own cells, eliminating the organ waiting list, but in the meantime we’ll settle for getting more drugs approved by the FDA at a significantly lower cost on an accelerated time scale, improving the quality of life for millions of people around the world.”
Tissue engineers have succeeded in making artificial organs that use a patient’s cells to become a living part of the body, with hope for eventual organ regeneration. So far, only a few organs have been made and transplanted, and they are relatively simple, hollow ones — like bladders and Mr. Beyene’s windpipe, which was implanted in June 2011. But scientists around the world are using similar techniques with the goal of building more complex organs. At Wake Forest University in North Carolina, for example, where the bladders were developed, researchers are working on kidneys, livers and more. Labs in China and the Netherlands are among many working on blood vessels. The work of these new body builders is far different from the efforts that produced artificial hearts decades ago. Those devices, which are still used temporarily by some patients awaiting transplants, are sophisticated machines, but in the end they are only that: machines. Tissue engineers aim to produce something that is more human. They want to make organs with the cells, blood vessels and nerves to become a living, functioning part of the body. Some, like Dr. Macchiarini, want to go even further — to harness the body’s repair mechanisms so that it can remake a damaged organ on its own. Researchers are making use of advances in knowledge of stem cells, basic cells that can be transformed into types that are specific to tissues like liver or lung. They are learning more about what they call scaffolds, compounds that act like mortar to hold cells in their proper place and that also play a major role in how cells are recruited for tissue repair. Tissue engineers caution that the work they are doing is experimental and costly, and that the creation of complex organs is still a long way off. But they are increasingly optimistic about the possibilities.
Efforts to create customised medicines using 3D printer-based technology are being developed in Glasgow. Researchers have used a £1,250 system to create a range of organic compounds and inorganic clusters - some of which are used to create cancer treatments. Longer term, the scientists say the process could be used to make customised medicines. It is predicted that this technique will be used by pharmaceutical firms within five years, and by the public within 20.
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