The Marriage of Biology and Engineering

Bioengineering’s most visible branch is the development of medical innovations such as prosthetics and high-tech implants, but genetic, stem cell and tissue engineering are all set to become key fields in the medicine of the future.

For example, to help prep a surgeon who needed to close the hole in an infant’s heart, a biomedical robotic expert at the Children’s National Medical Centre in Washington, DC created a model heart with a 3D printer. He used a mix of hard and soft plastics to replica the feel of a real heart.

A model heart created by 3D printer Photo: Carolyn Cochenour/Washington Post

In China medical doctors at the Orthopedic Hospital in Zhengzhou City created a 3D model of a dislocated spine. This allowed them to practice a complicated surgical procedure ahead of time…isolating and opening the problem area, resetting the dislocation and then screwing everything back together without damaging the patient’s actual spinal cord.


Model of a spine with a 3D-printed vertebra devise in Beijing Photograph: Jason Lee/Reuters

To rescue babies born with congenital breathing condition which caused their airways to collapse, the University of Michigan has customized tracheal splints made from biocompatible material.   The splints support the collapsed trachea and then get reabsorbed within two years.

Trachea splints Photo courtesy of Leisa Thompson, Photography/UNHA

Using bioengineering to create organ structures that function and restore the health of that tissue for that person, is the holy grail of bioengineering for regenerative medicine.

Scientists at Northwestern University created prosthetic ovaries for mice. The prosthetic ovaries were printed using liquid gelatin made from broken-down collagen, a natural material, which is found in ligaments, tendons, muscles, bones and skin.

A scaffold for a bioprosthetic mouse ovary 3D-printed with gelatin Photo by Kristin Samuelson

The research team 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. They then carefully inserted mouse follicles—spherical structures containing a growing egg surrounded by hormone-producing cells—into these “scaffolds.”

After punching out 2-millimeter circles through the scaffolds and implanting 40–50 follicles into each one, they created a “bioprosthetic” ovary. The team showed that blood vessels from each mouse infiltrated the scaffolds. This process 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 result was a fully functional bio-prosthetic ovary that not only restored hormone function, but also allowed the mice to get pregnant, deliver pups and lactate after birth.

In the future ready-to-implant organs should be possible in humans with 3D bioprinting. Scientists are excited that this technique could restore function in cancer patients who have lost their fertility.

Bioengineering is also being used to build artificial biological systems for research, engineering and medical applications.

Illustration of synthetic biology by Eric Proctor and Autumn Kulaga

Synthetic biology gives scientists unprecedented control of living cells at the genetic level. This field encompasses both plant and mammalian cells.

MIT biological engineers have created a programming language that allows them to rapidly design complex, DNA-encoded circuits to give new functions to living cells. The circuit runs inside a bacteria cell.   It’s like they are hacking living cells to program a new language.

Illustration of programing bacteria Image by Janet Iwasa

The MIT team plans to work on several different applications using this approach: bacteria that can be swallowed to aid in digestion of lactose; bacteria that can live on plant roots and produce insecticide if they sense the plant is under attack; and yeast that can be engineered to shut off when they are producing too many toxic byproducts in a fermentation reactor. In the future the bacteria could be programmed to release cancer drugs when encountering a tumor.

Biomedical engineering and biological programming are exciting, expanding new field of research with unlimited possibilities.

 

 

 

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Home is Where the Microbes Are

A person’s home is their castle and they populate it with their own subjects – millions and millions of bacteria.

When we move from one location to another we take all of our bacteria with us and “colonize” the space around us within a matter of hours. These “bacterial signatures” are unique.

Mouth microbes Credit Martin Oeggerli, with support from School of Life Sciences, FHNW

Microbiome studies could serve as a forensic tool. In the future scientists could look at bacterial colonies to identify the last person to come into contact with the victim of a crime and estimated when the contact happened.

Microbes on small intestines Credit: Stephanie Schuller

The human gut teems with bacteria, many of their species still unknown. They help us digest food and absorb nutrients, and they play a part in protecting our intestinal walls. Gut bacteria may also help regulate weight and ward off autoimmune diseases.

Chain of streptococcus in a lab sample. Credit: Photo by Martin Oeggerli, with support from School of Life Sciences, FHNW
Colored scanning electron micrograph of microbes in human gut Photo by Martin Oeggerli

What are “superbugs” ? Any bacteria that cannot be treated by two or more antibiotics is being called a superbug. The CDC claims the single leading factor for the increase in superbugs is the misuse of antibiotics. Most people who get a C. diff (Clostridium difficile) infection are getting medical care.

SEM by David Phillips of Clostridium Difficile

MRSA (Staphylococcus aureus) is carried by around 30 per cent of the population without causing any symptoms. However, in vulnerable people, such as those that have recently had surgery, it can cause wound infections, pneumonia and blood poisoning. MRSA cannot be treated with penicillin.

Staphylococcus aureus MRSA bacteria, computer artwork by Alfred Pasieka/Science Photo Library

Doctors sometimes recommend beneficial bacteria, also known as probiotics, for patients suffering from GI illnesses such as colitis and Crohn’s disease. However, these over-the-counter probiotic supplements may contain varying amounts of bacteria, and may include cells that are no longer viable. Furthermore, these probiotics have no protective coating, so they can be damaged by acid in the stomach before reaching the intestines.

An MIT team has come up with a method of coating these beneficial bacteria with layer-by-layer layers of polysaccharides or sugars. The thin, gel-like coating protects the bacteria cells from acid in the stomach, as well as bile salts. Once the cells reach the intestines, they settle in and begin replicating, creating a whole new microbiome.

MIT coated probiotic bacteria Credit: Second Bay Studios

 

 

Psychedelic Images in Science

3D Computed Tomography (CT) is a nondestructive scanning technology that allows you to view and inspect the external and internal structures of an object in 3D space. Computed Tomography works by taking hundreds or thousands of 2D Digital Radiography projections around a 360 degree rotation of an object. Algorithms are then used to reconstruct the 2D projections into a 3D CT volume, which will allow you to view and slice the part at any angle.

North Star Technology integrated circuit micro Chip 3D x ray nanotanomography ct scan
Integrated circuit micro chip shown using 3D nano tomography CT scan by North Star Technology

The same technology allows medical doctors and dentists to more accurately diagnose their patients and/or to view implants.

Brain Skull DawidKasza istockphoto 185555045
3D CT scan showing brain in human skull Credit:  DawidKasza/iStockphoto.com
Dental-CT-Scan showing implants
Dental 3D CT scan showing dental implants

In the course of developing sophisticated imaging techniques for peering into the human body, radiologist Dr. Kai-Hung Fung discovered something within himself: an artist.

Dr. Fung is a specialist in diagnostic radiology at Pamela Youde Nethersole Eastern Hospital, Hong Kong SAR, China. The discovery happened when Fung was asked by surgeons to generate 3-D images to allow them to visualize complex anatomies prior to surgery. Beginning with CT scans that show slices of organs at different depths, Fung stacked the slices into a single image and developed a way to indicate changes in depth with contour lines similar to those on a topographic map.

Teeth
Looking at human teeth upward from inside the mouth.  Credit:  Dr. Kai-Hung Fung
Kai Hung Fung CT scan cancerskulll
CT scan of human skull.  The red ring-like pattern is cancer of the thyroid, which has become detached and deposited on the skull bone.  Credit:  Dr. Kai-Hung Fung
Down through top of brain netwk arteries and veins Kai hung Fung blob1
Network of blood vessels inside the brain with the skull base as background.  Credit:  Dr. Kai-Hung Fung

Dr. Fung has used a post-production trick he developed, known as the “rainbow technique” to add colored contour lines to his images. This enhances the 3D effect.

Roof of 4th ventricle of brain K H Fung 1.jpg.CROP.original-original.jpg
Roof of 4th ventricle of brain  Credit:  Dr. Kai-Hung Fung

His approach to radiology doesn’t stop with medical imagery. He has partnered with Dr. Gary Yeoh to produce 3-D CT images of flowers and biological specimens.

Bell pepper (Capsicum annuum), 3D CT scan
Colored 3D CT scan of bell pepper.  Credit:  Dr. Kai-Hung Fung
Whelk, 3D CT scan
Colored 3D CT of whelk shell  Credit:  Dr. Kai-Hung Fung
Stargazer lily from mysicalgarden.org
Stargazer lily from mysticalgarden.org

Dr. Fung’s art career has blossomed. His amazing diagnostic images have been awarded, exhibited and published. His CT and MR scans are more than just psychedelic images, they are “4-D visualizations” that help surgeons visualize the changing perspectives and relative relationships of various anatomical structures.

Sticky Proteins Carry Vaccines

Successful vaccines and immune therapies contain more than just bits of harmful bugs; they also contain components that guide our immune response, making them more effective. Duke engineer Joel Collier and his group are hacking proteins’ natural ability to bend, fold, and assemble to create precisely blended vaccines. His team attaches important proteins (modeled here as red, cyan, and green) to short nanofiber segments (grey). When mixed, the proteins self-organize, creating a scaffold that delivers the perfect concoction of chemicals.

This image was chosen as a winner of the 2016 NIH funded research image call. Credit: Peter Allen

To see the entire gallery of 2016 NIH award winners go to https://www.flickr.com/photos/nihgov/albums/72157666897233564/

 

 

Sacrificing for the Greater Good

salmonella

Like American soldiers on the shores of Normandy during World War II, salmonella bacteria sacrifice themselves for the greater good — a phenomenon that may illuminate the evolution of altruism.

When salmonella enter the digestive tract, they fare poorly: other bacteria have already established their positions. But by sending an advance group digging into intestinal tissues, they set off an inflammatory reaction in their host, sweeping away the other bacteria. The advance group also dies, but the intestine is wide-open for colonization by their brethren. The population flourishes because of the selflessness of a few.

From a Darwinian viewpoint, the existence of altruism in nature is at first sight puzzling, as Darwin himself realized. Natural selection leads us to expect animals to behave in ways that increase their own chances of survival and reproduction, not those of others.

Alarm-calling monkey Credit: Vervet Monkey Sanctuary, Tzaneen, South Africa
Alarm-calling monkey Credit: Vervet Monkey Sanctuary, Tzaneen, South Africa

Here’s another example of sacrificiing for the greater good. Vervet monkeys give alarm calls to warn fellow monkeys of the presence of predators, even though by doing so they attract attention to themselves and increase their chance of being attacked. Biologists argue that the group that contains a high proportion of alarm-calling monkeys will have a survival advantage over a group containing a lower proportion, thereby encouraging this trait to continue and evolve among individuals. The Vervet monkey crier is Nature’s Hero. And Nature’s heroes are our real altruists.

Helping a relative is another example of animal altruism.

Two ants sharing food  Photo by Alex Wild
Two ants sharing food Photo by Alex Wild

The above photo shows nest mate workers engaging in the social sharing of liquid food. This behavior does more than merely transfer food. Ants also use it to pass chemical signals among each other, and research has shown that sharing food helps the colony maintain a cohesive identifying odor.

Two female worker ants.  Photo by Alex Wild
Two female worker ants. Photo by Alex Wild

Why are worker ants sterile? In most species, the balance between male and female is 50-50. But there are exceptions. In some ant species, for example, the ratio is around three daughters for every son. That is because the sterile female workers invest more into female larvae than males. The workers ants are more closely related to their sisters than to their brothers. A female ant may be able to spread more genes by helping to raise her queen mother’s eggs than trying to lay eggs of her own.

And finally interspecies animal adoptions are another example of altruism.

Mother cat nursing her own cat and abandoned puppies.  Credit:  Credit:  Muhammad Hamed/Reuters
Mother cat nursing her own cat and abandoned puppies. Credit: Credit: Muhammad Hamed/Reuters
Baby hippo that survived the Indian Ocean tsunami with his new “mother” a giant male Aldabran tortoise.  Credit:  Peter Greste/ATP/Getty Images.
Baby hippo that survived the Indian Ocean tsunami with his new “mother” a giant male Aldabran tortoise. Credit: Peter Greste/ATP/Getty Images.
Dog with adopted bunnies.  Credit:  Matt Jones via Flickr
Dog with adopted bunnies. Credit: Matt Jones via Flickr

Art & Medicine

A number of medical schools have adopted courses to train doctors in observational skills by studying great paintings. Physicians say the practice can help them become more observant, inform them about how society viewed medical conditions in the past, and connect them with the craft of medicine at a time when their profession is increasingly shaped by technological advances.

Modern doctors may be able to look to the paintings of Old Masters like Raphael and Rembrandt for practice in assessing their patients’ general health and finding clues about their ailments.

“The School of Athens” by Raphael    Credit:  Palazzi Pontifici, Vatican
“The School of Athens” by Raphael Credit: Palazzi Pontifici, Vatican

Note the detail shown below of Heraclitus from “The School of Athens” who represent Michelangelo, according to evidence of sketches by Michelangelo’s friend Vasari, and also in poetic depictions of his health problems by Michelangelo himself. The unusual shape of his knee might be a representation of gout, an acute form of arthritis.

Detail of Heraclitus from “The School of Athens” by Raphael
Detail of Heraclitus from “The School of Athens” by Raphael
"St. Peter Healing the Sick with his Shadow" by Masaccio   Credit: Brancacci Chapel, Santa Maria del Carmine, Florence, Italy
St. Peter Healing the Sick with his Shadow by Masaccio Credit: Brancacci Chapel, Santa Maria del Carmine, Florence, Italy

In Masaccio’s painting one of the figures represented in the bottom left corner looks like a polio victim:

Detail from St. Peter "Healing the Sick with his Shadow" by Masaccio
Detail from St. Peter “Healing the Sick with his Shadow” by Masaccio
"The Inheritance" by Edvard Munch    Credit:  Munch Museum, Oslo
“The Inheritance” by Edvard Munch Credit: Munch Museum, Oslo

“The Inheritance” is based on an experience Edvard Munch had at a hospital in Paris.   In a waiting room he observed a tear-stained mother with a dying child on her lap.   The child was infected with syphilis, a fatal venereal disease that can be passed from parent to child. The little child’s body is depicted with an abnormally large head, thin limbs, and a red rash on its chest.   The painting provoked strong reaction in Munch’s day boldly touching on many taboos such as sex, venereal diseases and even prostitution.

"A Family Group" by Thomas Jones Barker
“A Family Group” by Thomas Jones Barker

Some observers say the girl in the painting by Thomas Jones Barker which hangs in the Taj Hotel in Boston might have had Down Syndrome…see detail below:

Detail of "A Family Group" by Thomas Jones Barker
Detail of “A Family Group” by Thomas Jones Barker
  “Portrait of a Young Man” by Bronzino  Credit:  The Metropolitan Museum of Art/Art Resource, NY

“Portrait of a Young Man” by Bronzino Credit: The Metropolitan Museum of Art/Art Resource, NY

Doctors seem fascinated by the Italian Renaissance painter Bronzino’s “Portrait of A Young Man” and other portraits that show subjects with one eye that is shifted dramatically to one side. A number of doctors that saw these portraits diagnosed the sitters with strabismus, or “wandering eye.”

Will studying art make a better doctor? At least one class at Harvard’s Medical School meets at the Museum of Fine Arts. Weill Medical College of Cornell University has offered a noncredit art course in collaboration with the Frick Collection in New York City for eight years, while Yale Medical School runs an art observation course for medical students that is now a required class.

Sometimes, doctors look at symptoms and review tests but forget they are looking at human beings, which can lead them to miss something important in the diagnosis. Applying the skills learned in art history reinforces the fact that, as a doctor, you have to look at a person as a whole – not just the disease.

Super Resolution Microscopy

E. coli and Shigella sp. bacteria
Fluorescence confocal light micrograph of E. coli and Shigella sp. bacteria (blue) in human cell (green) Credit: Stephanie Schuller/Science Source
Fluorescent micrograph of human insulin producing beta cells  Credit:  Doug Melton/Harvard University.  Photo by B.D. Colen
Fluorescent micrograph of human insulin producing beta cells Credit: Doug Melton/Harvard University. Photo by B.D. Colen

It used to be fact, and even children at school were taught one basic principle of light microscopy: it’s impossible to see things that are smaller than 200 nanometers – that is, a 200 millionth of a millimeter. This was called the diffraction limit. So you might be able to see the shapes of very large bacteria or human cells under your microscope, but you won’t be able to see smaller structures inside of these cells or viruses and certainly no single molecules. This year three new Nobel Laureates in Chemistry – William E. Moerner, Stefan W. Hell and Eric Betzig – have turned it all on its head with the development of super-resolved fluorescence microscopy.

Stefan Hell developed a special method which makes use of two laser beams. One stimulates fluorescent molecules to glow. A second laser beam, though, cancels out any glow caused by the first beam – except for that in a nanometer-sized volume. This way, he yielded images with a resolution much better than conventional confocal light microscopes. He called the new microscopy STED – stimulated emission depletion microscopy.

Working separately Moerner and Betzig, using the same concept of fluorescence and turning individual molecules on and off with laser beam pulses, made it possible to see single molecules only one nanometer big under a microscope.

This image demonstrates the difference in resolution of confocal and STED microscopy. It shows proteins of the nucleus, labeled with fluorescent dyes, imaged with a STED microscope.
This image demonstrates the difference in resolution of confocal and STED microscopy. It shows proteins of the nucleus, labeled with fluorescent dyes, imaged with a STED microscope.
Difference between confocual and super resolution view of a human cell.  Credit:  Dr. Dr. Kandasamy Biomedical Microscopy Core University of Georgia.
Difference between confocual and super resolution view of a human cell. Credit: Dr. Dr. Kandasamy Biomedical Microscopy Core University of Georgia.

Since this technology can be used with living cells it will be an invaluable resource when studying HIV or to observe how living cancer cells react to certain cancer drugs. Biologists will even be able to study nerve synapses and the interaction between viruses and cells. This will be a rapidly expanding field in many, many branches of science.

Super-resolution image of a living neuron captured on STED reveals dendritic spines in unprecedented detail.  Photo by Stefen Hell from the Max Planck Institute on Biophysical Chemistry.
Super-resolution image of a living neuron captured on STED reveals dendritic spines in unprecedented detail. Photo by Stefen Hell from the Max Planck Institute on Biophysical Chemistry.
Protein network in a mammalian cell captured with STED Photo from Max Planck Institute of Biophysical Chemistry
Protein network in a mammalian cell captured with STED Photo from Max Planck Institute of Biophysical Chemistry

To watch a video on the STED microscope produced by the Max Planck Institute click below.