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Biomedical Engineering

Growing laboratory-engineered miniature human livers

I enjoyed eating cow liver as a kid. I never understood why so many kids thought it was bad. It was and still is one of my favorite foods. Now, one day soon, I might just be able to grow my own livers for snacking anytime I'd like. And the bonus is that if my own liver wears out or fails I might be able to have a surgeon pop a new one in. Well it might not be quite that simple. But in the quest to grow replacement human organs in the lab, livers are no doubt at the top of many a wish list. With its wide range of functions that support almost every organ in the body and no way to compensate for the absence of liver function, the ability to grow a replacement is also the focus of many research efforts. Now, for the first time, researchers have been able to successfully engineer miniature livers in the lab using human liver cells.

The ultimate aim of the research carried out at the Institute for Regenerative Medicine at Wake Forest University Baptist Medical Center is to provide a solution to the shortage of donor livers available for patients who need transplants. Additionally, the laboratory-engineered livers could also be used to test the safety of new drugs.

The livers engineered by the researchers are about an inch in diameter and weigh about 0.2 ounces (5.7 g). Even though the average weight of an adult human liver is around 4.4 pounds (2 kg), to meet to minimum needs of the human body the scientists say an engineered liver would need to weigh about one pound (454 g) because research has shown that human livers functioning at 30 percent of capacity are able to sustain the human body.

“We are excited about the possibilities this research represents, but must stress that we’re at an early stage and many technical hurdles must be overcome before it could benefit patients,” said Shay Soker, Ph.D., professor of regenerative medicine and project director. “Not only must we learn how to grow billions of liver cells at one time in order to engineer livers large enough for patients, but we must determine whether these organs are safe to use in patients.”

How the livers were engineered

To engineer the organs, the scientists took animal livers and treated them with a mild detergent to remove all cells in a process called decellularization. This left only the collagen “skeleton” or support structure which allowed the scientists to replace the original cells with two types of human cells: immature liver cells known as progenitors, and endothelial cells that line blood vessels.

Because the network of vessels remains intact after the decellularization process the researchers were able to introduce the cells into the liver skeleton through a large vessel that feeds a system of smaller vessels in the liver. The liver was then placed in a bioreactor, special equipment that provides a constant flow of nutrients and oxygen throughout the organ.

Flexible biocompatible LEDs for next gen biomedicine

Researchers from the University of Illinois at Urbana-Champaign have created bio-compatible LED arrays that can bend, stretch, and even be implanted under the skin. You can see an example of this in the image as LEDs have been embedded under an animal's skin.
While getting a glowing tattoo would be awesome, the arrays are actually intended for activating drugs, monitoring medical conditions, or performing other biomedical tasks within the body. Down the road, however, they could also be incorporated into consumer goods, robotics, or military/industrial applications.
Many groups have been trying to produce flexible electronic circuits, most of those incorporating new materials such as carbon nanotubes combined with silicon. The U Illinois arrays, by contrast, use the traditional semiconductor gallium arsenide (GaAs) and conventional metals for diodes and detectors.
Last year, by stamping GaAs-based components onto a plastic film, Prof. John Rogers and his team were able to create the array’s underlying circuit. Recently, they added coiled interconnecting metal wires and electronic components, to create a mesh-like grid of LEDs and photodetectors. That array was added to a pre-stretched sheet of rubber, which was then itself encapsulated inside another piece of rubber, this one being bio-compatible and transparent.
The resulting device can be twisted or stretched in any direction, with the electronics remaining unaffected after being repeatedly stretched by up to 75 percent. The coiled wires, which spring back and forth like a telephone cord, are the secret to its flexibility.
Rogers and his associates are now working on commercializing their biocompatible flexible LED array via their startup company, mc10.
The research was recently published in the journal Nature Materials.

watching nanoparticles grow

I have spent a lot of time over the past decade-and-a-half talking about nanotech and nanoparticles. The often unexpected properties of these tiny specks of matter are give them applications in everything from synthetic antibodies to fuel cells to water filters and far beyond.
Recently, for the first time ever, scientists were able to watch the particles grow from their earliest stage of development. Given that the performance of nanoparticles is based on their structure, composition, and size, being able to see how they grow could lead to the development of better growing conditions, and thus better nanotechnology.
The research was carried out by a team of scientists from the Center for Nanoscale Materials, the Advanced Photon Source (both run by US Government's Argonne National Laboratory) and the High Pressure Synergetic Consortium (HPSynC).
The team used highly focused high-energy X-ray diffraction to observe the nanoparticles. Amongst other things, it was noted that the initial chemical reaction often occurred quite quickly, then continued to evolve over time.
“It’s been very difficult to watch these tiny particles be born and grow in the past because traditional techniques require that the sample be in a vacuum and many nanoparticles are grown in a metal-conducting liquid,” said study coauthor Wenge Yang. “We have not been able to see how different conditions affect the particles, much less understand how we can tweak the conditions to get a desired effect.”
HPSynC’s Russell Hemley added, “This study shows the promise of new techniques for probing crystal growth in real time. Our ultimate goal is to use these new methods to track chemical reactions as they occur under a variety of conditions, including variable pressures and temperatures, and to use that knowledge to design and make new materials for energy applications.”
The research was recently published in the journal NANOLetters.

‘Artificial ovary’ allows human eggs to be matured outside the body

 

In a move that could yield infertility treatments for cancer patients and provide a powerful new means for conducting fertility research, researchers have built an artificial human ovary that can grow oocytes into mature human eggs in the laboratory. The ovary not only provides a living laboratory for investigating fundamental questions about how healthy ovaries work, but also can act as a testbed for seeing how problems, such as exposure to toxins or other chemicals, can disrupt egg maturation and health. It could also allow immature eggs, salvaged and frozen from women facing cancer treatment, to be matured outside the patient in the artificial ovary.
To create the ovary, the researchers at Brown University and Women & Infants Hospital formed honeycombs of theca cells, one of two key types of cells in the ovary, donated by reproductive-age (25-46) patients at the hospital. After the theca cells grew into the honeycomb shape, spherical clumps of donated granulosa cells were inserted into the holes of the honeycomb together with human egg cells, known as oocytes. In a couple days the theca cells enveloped the granulosa and eggs, mimicking a real ovary. In experiments the structure was able to nurture eggs from the “early antral follicle” stage to mature human eggs.
Sandra Carson, professor of obstetrics and gynecology at the Warren Alpert Medical School of Brown University and director of the Division of Reproductive Endocrinology and Infertility at Women & Infants Hospital, said her goal was never to invent an artificial organ, per se, but merely create a research environment in which she could study how theca and granulose cells and oocytes interact. She then heard of the so-called “3D Petri dishes” developed by Jeffrey Morgan that are made of a moldable agarose gel that provides a nurturing template to encourage cells to assemble into specific shapes. The two then teamed up to create the organ, resulting in the first fully functioning tissue to be made using Morgan’s method.
The paper detailing the development of the artificial ovary appears in the Journal of Assisted Reproduction and Genetics.

 

Mind-controlled prosthetics without brain surgery

Mind-reading is powerful stuff, but what about hand-reading? Intricate, three-dimensional hand motions have been "read" from the brain using nothing but scalp electrodes. The achievement brings closer the prospect of thought-controlled prosthetics that do not require brain surgery.

Electroencephalography (EEG), which measures electrical activity through the scalp, was previously considered too insensitive to relay the neural activity involved in complex movements of the hands. Nevertheless, Trent Bradberry and colleagues at the University of Maryland, College Park, thought the idea worth investigating.

The team used EEG to measure the brain activity of five volunteers as they moved their hands in three dimensions, and also recorded the movement detected by motion sensors attached to the volunteers' hands. They then correlated the two sets of readings to create a mathematical model that converts one into the other.

In additional trials, this model allowed Bradberry's team to use the EEG readings to accurately monitor the speed and position of each participant's hand in three dimensions.

If EEG can, contrary to past expectation, be used to monitor complex hand movements, it might also be used to control a prosthetic arm, Bradberry suggests. EEG is less invasive and less expensive than the implanted electrodes, which have previously been used to control robotic arms and computer cursors by thought alone, he says.

Giving Prosthetic Limbs The Sense Of Touch

When I was a child I dreamt about one day becoming a biomedical engineer. And, somewhere in my mother's attic lies the remnants of that dream in the form of school papers and crayon drawings of the limbs, heads, and torsos that I one day hoped to design, engineer, and implant on human beings and animals. Aside from making me the creepiest kid in the neighborhood this also provided me with a special way of thinking about the interconnections and relationships between machines and people. That dream ultimately evaporated in college when I chose to start monetizing my software development hobby instead of completing my inorganic chemistry studies.

Today however actual biomedical engineers have come one step close to the giving a sense of touch to prosthetics for humans. Existing robotic prostheses have limited motor control, provide no sensory feedback and can be uncomfortable to wear. In an effort to make a prosthesis that moves like a normal hand, researchers at the University of Michigan (U-M) have bioengineered a scaffold that is placed over severed nerve endings like a sleeve and could improve the function of prosthetic hands and possibly restore the sense of touch for injured patients.


To overcome the limitations of existing prostheses, the U-M researchers realized a better nerve interface was needed to control the upper extremity prostheses. So they created what they called an “artificial neuromuscular junction” composed of muscle cells and a nano-sized polymer placed on a biological scaffold. Neuromuscular junctions are the body's own nerve-muscle connections that enable the brain to control muscle movement.

When a hand is amputated, the nerve endings in the arm continue to sprout branches, growing a mass of nerve fibers that send flawed signals back to the brain. The bioengineered scaffold was placed over the severed nerve endings like a sleeve. The muscle cells on the scaffold and in the body bonded and the body's native nerve sprouts fed electrical impulses into the tissue, creating a stable nerve-muscle connection.

In laboratory rats, the bioengineered interface relayed both motor and sensory electrical impulses and created a target for the nerve endings to grow properly. This indicates that the interface may not only improve fine motor control of prostheses, but can also relay sensory perceptions such as touch and temperature back to the brain. Laboratory rats with the interface responded to tickling of feet with appropriate motor signals to move the limb.


The research project, which was funded by the Department of Defense, arose from a need for better prosthetic devices for troops wounded in Afghanistan and Iraq. The DoD and the Army have already provided $4.5 million in grants to support the research. Meanwhile, the University of Michigan research team has submitted a proposal to the Defense Advance Research Project Agency (DARPA) to begin testing the bioengineered interface in humans in three years.