Tag Archives: bioengineering

Brain and machine as one (machine/flesh)

The essay on brains and machines becoming intertwined is making the rounds. First stop on my tour was its Oct. 4, 2016 appearance on the Mail & Guardian, then there was its Oct. 3, 2016 appearance on The Conversation, and finally (moving forward in time) there was its Oct. 4, 2016 appearance on the World Economic Forum website as part of their Final Frontier series.

The essay was written by Richard Jones of Sheffield University (mentioned here many times before but most recently in a Sept. 4, 2014 posting). His book ‘Soft Machines’ provided me with an important and eminently readable introduction to nanotechnology. He is a professor of physics at the University of Sheffield and here’s more from his essay (Oct. 3, 2016 on The Conversation) about brains and machines (Note: Links have been removed),

Imagine a condition that leaves you fully conscious, but unable to move or communicate, as some victims of severe strokes or other neurological damage experience. This is locked-in syndrome, when the outward connections from the brain to the rest of the world are severed. Technology is beginning to promise ways of remaking these connections, but is it our ingenuity or the brain’s that is making it happen?

Ever since an 18th-century biologist called Luigi Galvani made a dead frog twitch we have known that there is a connection between electricity and the operation of the nervous system. We now know that the signals in neurons in the brain are propagated as pulses of electrical potential, whose effects can be detected by electrodes in close proximity. So in principle, we should be able to build an outward neural interface system – that is to say, a device that turns thought into action.

In fact, we already have the first outward neural interface system to be tested in humans. It is called BrainGate and consists of an array of micro-electrodes, implanted into the part of the brain concerned with controlling arm movements. Signals from the micro-electrodes are decoded and used to control the movement of a cursor on a screen, or the motion of a robotic arm.

A crucial feature of these systems is the need for some kind of feedback. A patient must be able to see the effect of their willed patterns of thought on the movement of the cursor. What’s remarkable is the ability of the brain to adapt to these artificial systems, learning to control them better.

You can find out more about BrainGate in my May 17, 2012 posting which also features a video of a woman controlling a mechanical arm so she can drink from a cup coffee by herself for the first time in 15 years.

Jones goes on to describe the cochlear implants (although there’s no mention of the controversy; not everyone believes they’re a good idea) and retinal implants that are currently available. Jones notes this (Note Links have been removed),

The key message of all this is that brain interfaces now are a reality and that the current versions will undoubtedly be improved. In the near future, for many deaf and blind people, for people with severe disabilities – including, perhaps, locked-in syndrome – there are very real prospects that some of their lost capabilities might be at least partially restored.

Until then, our current neural interface systems are very crude. One problem is size; the micro-electrodes in use now, with diameters of tens of microns, may seem tiny, but they are still coarse compared to the sub-micron dimensions of individual nerve fibres. And there is a problem of scale. The BrainGate system, for example, consists of 100 micro-electrodes in a square array; compare that to the many tens of billions of neurons in the brain. The fact these devices work at all is perhaps more a testament to the adaptability of the human brain than to our technological prowess.

Scale models

So the challenge is to build neural interfaces on scales that better match the structures of biology. Here, we move into the world of nanotechnology. There has been much work in the laboratory to make nano-electronic structures small enough to read out the activity of a single neuron. In the 1990s, Peter Fromherz, at the Max Planck Institute for Biochemistry, was a pioneer of using silicon field effect transistors, similar to those used in commercial microprocessors, to interact with cultured neurons. In 2006, Charles Lieber’s group at Harvard succeeded in using transistors made from single carbon nanotubes – whiskers of carbon just one nanometer in diameter – to measure the propagation of single nerve pulses along the nerve fibres.

But these successes have been achieved, not in whole organisms, but in cultured nerve cells which are typically on something like the surface of a silicon wafer. It’s going to be a challenge to extend these methods into three dimensions, to interface with a living brain. Perhaps the most promising direction will be to create a 3D “scaffold” incorporating nano-electronics, and then to persuade growing nerve cells to infiltrate it to create what would in effect be cyborg tissue – living cells and inorganic electronics intimately mixed.

I have featured Charles Lieber and his work here in two recent posts: ‘Bionic’ cardiac patch with nanoelectric scaffolds and living cells on July 11, 2016 and Long-term brain mapping with injectable electronics on Sept. 22, 2016.

For anyone interested in more about the controversy regarding cochlear implants, there’s this page on the Brown University (US) website. You might also want to check out Gregor Wolbring (professor at the University of Calgary) who has written extensively on the concept of ableism (links to his work can be found at the end of this post). I have excerpted from an Aug. 30, 2011 post the portion where Gregor defines ‘ableism’,

From Gregor’s June 17, 2011 posting on the FedCan blog,

The term ableism evolved from the disabled people rights movements in the United States and Britain during the 1960s and 1970s.  It questions and highlights the prejudice and discrimination experienced by persons whose body structure and ability functioning were labelled as ‘impaired’ as sub species-typical. Ableism of this flavor is a set of beliefs, processes and practices, which favors species-typical normative body structure based abilities. It labels ‘sub-normative’ species-typical biological structures as ‘deficient’, as not able to perform as expected.

The disabled people rights discourse and disability studies scholars question the assumption of deficiency intrinsic to ‘below the norm’ labeled body abilities and the favoritism for normative species-typical body abilities. The discourse around deafness and Deaf Culture would be one example where many hearing people expect the ability to hear. This expectation leads them to see deafness as a deficiency to be treated through medical means. In contrast, many Deaf people see hearing as an irrelevant ability and do not perceive themselves as ill and in need of gaining the ability to hear. Within the disabled people rights framework ableism was set up as a term to be used like sexism and racism to highlight unjust and inequitable treatment.

Ableism is, however, much more pervasive.

You can find out more about Gregor and his work here: http://www.crds.org/research/faculty/Gregor_Wolbring2.shtml or here:
https://www.facebook.com/GregorWolbring.

Cutting into a cell with a nanoblade

A May 11, 2016 news item on Nanotechnology Now features a type of surgery that could aid in cell engineering,

To study certain aspects of cells, researchers need the ability to take the innards out, manipulate them, and put them back. Options for this kind of work are limited, but researchers reporting May 10 [2016] in Cell Metabolism describe a “nanoblade” that can slice through a cell’s membrane to insert mitochondria. The researchers have previously used this technology to transfer other materials between cells and hope to commercialize the nanoblade for wider use in bioengineering.

Caption: This diagram illustrates the process of transferring mitochondria between cells using the nanoblade technology. Credit: Alexander N. Patananan Courtesy UCLA

Caption: This diagram illustrates the process of transferring mitochondria between cells using the nanoblade technology.
Credit: Alexander N. Patananan Courtesy UCLA

A May 10, 2016 Cell Press news release on EurekAlert, which originated the news item, expands on the theme,

“As a new tool for cell engineering, to truly engineer cells for health purposes and research, I think this is very unique,” says Mike Teitell, a pathologist and bioengineer at the University of California, Los Angeles (UCLA). “We haven’t run into anything so far, up to a few microns in size, that we can’t deliver.”

Teitell and Pei-Yu “Eric” Chiou, also a bioengineer at UCLA, first conceived the idea of a nanoblade several years ago to transfer a nucleus from one cell to another. However, they soon delved into the intersection of stem cell biology and energy metabolism, where the technology could be used to manipulate a cell’s mitochondria. Studying the effects of mutations in the mitochondrial genome, which can cause debilitating or fatal diseases in humans, is tricky for a number of reasons.

“There’s a bottleneck in the field for modifying a cell’s mitochondrial DNA,” says Teitell. “So we are working on a two-step process: edit the mitochondrial genome outside of a cell, and then take those manipulated mitochondria and put them back into the cell. We’re still working on the first step, but we’ve solved that second one quite well.”

The nanoblade apparatus consists of a microscope, laser, and titanium-coated micropipette to act as the “blade,” operated using a joystick controller. When a laser pulse strikes the titanium, the metal heats up, vaporizing the surrounding water layers in the culture media and forming a bubble next to a cell. Within a microsecond, the bubble expands, generating a local force that punctures the cell membrane and creates a passageway several microns long that the “cargo”–in this case, mitochondria–can be pushed through. The cell then rapidly repairs the membrane defect.

Teitell, Chiou, and their team used the nanoblade to insert tagged mitochondria from human breast cancer cells and embryonic kidney cells into cells without mitochondrial DNA. When they sequenced the nuclear and mitochondrial DNA afterwards, the researchers saw that the mitochondria had been successfully transferred and replicated by 2% of the cells, with a range of functionality. Other methods of mitochondrial transfer are hard to control, and when they have been reported to work, the success rates have been only 0.0001%-0.5% according to the researchers.

“The success of the mitochondrial transfer was very encouraging,” says Chiou. “The most exciting application for the nanoblade, to me, is in the study of mitochondria and infectious diseases. This technology brings new capabilities to help advance these fields.”

The team’s aspirations also go well beyond mitochondria, and they’ve already scaled up the nanoblade apparatus into an automated high-throughput version. “We want to make a platform that’s easy to use for everyone and allow researchers to devise anything they can think of a few microns or smaller that would be helpful for their research–whether that’s inserting antibodies, pathogens, synthetic materials, or something else that we haven’t imagined,” says Teitell. “It would be very cool to allow people to do something that they can’t do right now.”

The pipette being used is measured at the microscale but it’s called a nanoblade? Well, perhaps the tip or the edge of the pipette is measured at the nanoscale.

Getting back to the research, here’s a link to and a citation for the paper,

Mitochondrial Transfer by Photothermal Nanoblade Restores Metabolite Profile in Mammalian Cells by Ting-Hsiang Wu, Enrico Sagullo, Dana Case, Xin Zheng, Yanjing Li, Jason S. Hong, Tara TeSlaa, Alexander N. Patananan, J. Michael McCaffery, Kayvan Niazi, Daniel Braas, Carla M. Koehler, Thomas G. Graeber, Pei-Yu Chiou, Michael A. Teitell. Cell Metabolism Volume 23, Issue 5, p921–929, 10 May 2016  DOI: http://dx.doi.org/10.1016/j.cmet.2016.04.007

This paper appears to be open access.

Hydrogels and cartilage; repurposing vehicles in space; big bang has ‘fingerprints’

The American Institute of Physics (AIP) has made a selection of four articles freely available (h/t Mar. 9, 2015 news item on Azonano).

From a March 6, 2015 AIP news release,

WASHINGTON D.C., March 6, 2015 — The following articles are freely available online from Physics Today (www.physicstoday.org), the world’s most influential and closely followed magazine devoted to physics and the physical science community.

You are invited to read, share, blog about, link to, or otherwise enjoy:

1) STIFF AND SUPPLE CARTILAGE SUBSTITUTE

Physics Today‘s Ashley Smart reports on hydrogels that mimic the tricky nature of cartilage thanks to magnetically aligned nanosheets.

“In the realm of bioengineering, hydrogels are something of an all-purpose material. Made up of networks of interlinked, hydrophilic polymers, they tend to be soft, biocompatible, and highly absorbent…. The new material mimics the articular cartilage that lubricates our joints: It can support a heavy load along one direction while stretching and shearing with ease in the others.”

MORE: http://dx.doi.org/10.1063/PT.3.2707

2) GIVING SPACECRAFT A SECOND LEASE ON LIFE WHILE HURTLING THROUGH THE COSMOS

Physics Today‘s Toni Feder reports on the innovative processes undertaken to repurpose various spacecraft in flight, including Kepler, Voyager, Deep Impact, Spitzer, and the Hubble Space Telescope.

“A comeback like Kepler’s is ‘not unique, but it’s unusual,’ says Derek Buzasi of Florida Gulf Coast University, who reinvented the Wide-Field Infrared Explorer (WIRE) after it failed following its 1999 launch. ‘Spacecraft are built for a specialized purpose, so they are hard to repurpose. You have to come up with something they are capable of at the same time they are incapable of their original mission.’

Deep Impact’s original mission was to hurl a copper ball at a comet and watch the impact. In its continued form as EPOXI, the spacecraft went on to visit another comet and, on the way, served as an observatory for user- proposed targets.”

MORE: http://dx.doi.org/10.1063/PT.3.2713

3) CONGRESSMAN & FUSION RESEARCHER REFLECTS ON SCIENCE POLICY

Physics Today‘s David Kramer interviews Rush Holt, the New Jersey congressman who retired from office and this past December took the helm of the American Association for the Advancement of Science.

“PT: What do you consider to be your accomplishments in Congress?

HOLT: I focused a lot on science education. Our real problem is not that we’re failing to produce excellent scientists, because we are [producing them], but rather that we have failed to maintain an appreciation for and understanding of science in the general population. I was able to keep a spotlight on the need but wasn’t able to accomplish as much as I wanted. We got science included in the subjects emphasized by federal law. But we haven’t really improved teacher professional development and other things we need to do.”

MORE: http://dx.doi.org/10.1063/PT.3.2714

4) PARTICLE PHYSICS AND THE COSMIC MICROWAVE BACKGROUND

In this article, physics researchers John Carlstrom, Tom Crawford and Lloyd Knox discuss the fingerprints of the Big Bang and quantum fluctuations in the early universe, which may soon reveal physics at unprecedented energy scales.

“With its empirical successes, inflation is by consensus the best paradigm—notwithstanding some notable dissenting views—for the mechanism that generated the primordial density fluctuations that led to all structure in the universe. Its success has motivated physicists to search for the siblings of those fluctuations, the gravitational waves, via their signature in the polarization of the CMB. If discovered, that gravitational imprint would open up an observational window onto quantum gravitational effects, extremely early times, and extremely high energies.”

MORE: http://dx.doi.org/10.1063/PT.3.2718

I have checked; all of the links do lead to the articles.

Medical nanobots (nanorobots) and biocomputing; an important step in Russia

Russian researchers have reported a technique which can make logical calculations from within cells according to an Aug. 19, 2014 news item on ScienceDaily,

Researchers from the Institute of General Physics of the Russian Academy of Sciences, the Institute of Bioorganic Chemistry of the Russian Academy of Sciences and MIPT [Moscow Institute of Physics and Technology] have made an important step towards creating medical nanorobots. They discovered a way of enabling nano- and microparticles to produce logical calculations using a variety of biochemical reactions.

An Aug. 19 (?), 2014 MIPT press release, which originated the news item, provides a good beginner’s explanation of bioengineering in the context of this research,

For example, modern bioengineering techniques allow for making a cell illuminate with different colors or even programming it to die, linking the initiation  of apoptosis [cell death] to the result of binary operations.

Many scientists believe logical operations inside cells or in artificial biomolecular systems to be a way of controlling biological processes and creating full-fledged micro-and nano-robots, which can, for example, deliver drugs on schedule to those tissues where they are needed.

Calculations using biomolecules inside cells, a.k.a. biocomputing, are a very promising and rapidly developing branch of science, according to the leading author of the study, Maxim Nikitin, a 2010 graduate of MIPT’s Department of Biological and Medical Physics. Biocomputing uses natural cellular mechanisms. It is far more difficult, however, to do calculations outside cells, where there are no natural structures that could help carry out calculations. The new study focuses specifically on extracellular biocomputing.

The study paves the way for a number of biomedical technologies and differs significantly from previous works in biocomputing, which focus on both the outside and inside of cells. Scientists from across the globe have been researching binary operations in DNA, RNA and proteins for over a decade now, but Maxim Nikitin and his colleagues were the first to propose and experimentally confirm a method to transform almost any type of nanoparticle or microparticle into autonomous biocomputing structures that are capable of implementing a functionally complete set of Boolean logic gates (YES, NOT, AND and OR) and binding to a target (such as a cell) as result of a computation. This method allows for selective binding to target cells, as well as it represents a new platform to analyze blood and other biological materials.

The prefix “nano” in this case is not a fad or a mere formality. A decrease in particle size sometimes leads to drastic changes in the physical and chemical properties of a substance. The smaller the size, the greater the reactivity; very small semiconductor particles, for example, may produce fluorescent light. The new research project used nanoparticles (i.e. particles of 100 nm) and microparticles (3000 nm or 3 micrometers).

Nanoparticles were coated with a special layer, which “disintegrated” in different ways when exposed to different combinations of signals. A signal here is the interaction of nanoparticles with a particular substance. For example, to implement the logical operation “AND” a spherical nanoparticle was coated with a layer of molecules, which held a layer of spheres of a smaller diameter around it. The molecules holding the outer shell were of two types, each type reacting only to a particular signal; when in contact with two different substances small spheres separated from the surface of a nanoparticle of a larger diameter. Removing the outer layer exposed the active parts of the inner particle, and it was then able to interact with its target. Thus, the team obtained one signal in response to two signals.

For bonding nanoparticles, the researchers selected antibodies. This also distinguishes their project from a number of previous studies in biocomputing, which used DNA or RNA for logical operations. These natural proteins of the immune system have a small active region, which responds only to certain molecules; the body uses the high selectivity of antibodies to recognize and neutralize bacteria and other pathogens.

Making sure that the combination of different types of nanoparticles and antibodies makes it possible to implement various kinds of logical operations, the researchers showed that cancer cells can be specifically targeted as well. The team obtained not simply nanoparticles that can bind to certain types of cells, but particles that look for target cells when both of two different conditions are met, or when two different molecules are present or absent. This additional control may come in handy for more accurate destruction of cancer cells with minimal impact on healthy tissues and organs.

Maxim Nikitin said that although this is just as mall step towards creating efficient nanobiorobots, this area of science is very interesting and opens up great vistas for further research, if one draws an analogy between the first works in the creation of nanobiocomputers and the creation of the first diodes and transistors, which resulted in the rapid development of electronic computers.

Here’s a link to and a citation for the paper,

Biocomputing based on particle disassembly by Maxim P. Nikitin, Victoria O. Shipunova, Sergey M. Deyev, & Petr I. Nikitin. Nature Nanotechnology (2014) doi:10.1038/nnano.2014.156 Published online 17 August 2014

This paper is behind a paywall.

Growing a tooth—as an adult

These days it seems that teeth are the most erogenous zone of all. Actors on screens of all types flash pearly whites that are increasingly blinding while the rest of us are enjoined to buy teeth whiteners in toothpastes, mouthwashes, whitening strips, and/or find dental professionals to assist us in our quest for the brightest and whitest teeth. It would all be so much easier if we could just grow new teeth and discard the old ones.

Coincidentally or not, it seems researchers at King’s College London have also been thinking about how we might grow new teeth. Ben Schiller in a Mar. 14, 2013 article for Fast Company highlights the work,

Researchers from the U.K. have successfully bioengineered teeth from gum tissue and cells taken from mice. By combining and transplanting two groups of cells, they were able to grow full teeth, complete with roots, dentine, and enamel.

This King’s College London Mar. 11, 2013 news release provides more details,

New research published in the Journal of Dental Research describes an advance in efforts to develop a method to replace missing teeth with new bioengineered teeth generated from a person’s own gum cells. …

Current implant-based methods of whole tooth replacement fail to reproduce a natural root structure and as a consequence of the friction from eating and other jaw movement, loss of jaw bone can occur around the implant.

Research towards achieving the aim of producing bioengineered teeth (bioteeth) has largely focused on the generation of immature teeth (teeth primordia) that mimic those in the embryo that can be transplanted as small cell ‘pellets’ into the adult jaw to develop into functional teeth. Remarkably, despite the very different environments, embryonic teeth primordia can develop normally in the adult mouth and thus if suitable cells can be identified that can be combined in such a way to produce an immature tooth, there is a realistic prospect bioteeth can become a clinical reality. Subsequent studies have largely focussed on the use of embryonic cells and although it is clear that embryonic tooth primordia cells can readily form immature teeth following dissociation into single cell populations and subsequent recombination, such cell sources are impractical to use in a general therapy.

Professor Sharpe [Paul Sharpe, an expert in craniofacial development and stem cell biology at King’s College London’s Dental Institute] said: ‘What is required is the identification of adult sources of human epithelial and mesenchymal cells that can be obtained in sufficient numbers to make biotooth formation a viable alternative to dental implants.’

In this new work, the researchers isolated adult human gum (gingival) tissue from patients at the Dental Institute at King’s College London, grew more of it in the lab, and then combined it with the cells of mice that form teeth (mesenchyme cells). By transplanting this combination of cells into mice the researchers were able to grow hybrid human/mouse teeth containing dentine and enamel, as well as viable roots.

Professor Sharpe concluded: ‘Epithelial cells derived from adult human gum tissue are capable of responding to tooth inducing signals from embryonic tooth mesenchyme in an appropriate way to contribute to tooth crown and root formation and give rise to relevant differentiated cell types, following in vitro culture. These easily accessible epithelial cells are thus a realistic source for consideration in human biotooth formation. The next major challenge is to identify a way to culture adult human mesenchymal cells to be tooth-inducing, as at the moment we can only make embryonic mesenchymal cells do this.’

If I read this rightly, researchers are several years away from actually growing a new tooth in an adult human mouth but this work suggests they might be on the right research track.

Bioengineered ear at Cornell University

The researchers claim their bioengineered ear looks and acts like a real ear, from the Feb. 20, 2013 news release on EurekAlert,

Cornell bioengineers and physicians have created an artificial ear – using 3-D printing and injectable molds – that looks and acts like a natural ear, giving new hope to thousands of children born with a congenital deformity called microtia.

In a study published online Feb. 20 in PLOS ONE, Cornell biomedical engineers and Weill Cornell Medical College physicians described how 3-D printing and injectable gels made of living cells can fashion ears that are practically identical to a human ear. Over a three-month period, these flexible ears grew cartilage to replace the collagen that was used to mold them.

“This is such a win-win for both medicine and basic science, demonstrating what we can achieve when we work together,” said co-lead author Lawrence Bonassar, associate professor of biomedical engineering.

The novel ear may be the solution reconstructive surgeons have long wished for to help children born with ear deformity, said co-lead author Dr. Jason Spector, director of the Laboratory for Bioregenerative Medicine and Surgery and associate professor of plastic surgery at Weill Cornell in New York City.

“A bioengineered ear replacement like this would also help individuals who have lost part or all of their external ear in an accident or from cancer,” Spector said.

Replacement ears are usually constructed with materials that have a Styrofoam-like consistency, or sometimes, surgeons build ears from a patient’s harvested rib. This option is challenging and painful for children, and the ears rarely look completely natural or perform well, Spector said.

Lawrence Bonassar, associate professor of biomedical engineering, and colleagues collaborated with Weill Cornell Medical College physicians to create an artificial ear using 3-D printing and injectable molds. Credit: Lindsay France/University Photography [downloaded from http://www.news.cornell.edu/stories/Feb13/earPrint.html]

Lawrence Bonassar, associate professor of biomedical engineering, and colleagues collaborated with Weill Cornell Medical College physicians to create an artificial ear using 3-D printing and injectable molds. Credit: Lindsay France/University Photography [downloaded from http://www.news.cornell.edu/stories/Feb13/earPrint.html]

A Feb. 20, 2013 article in Cornell University’s Chronicle Online (and the basis for the news release) provides details about how this bioengineered ear was achieved (Note: A link has been removed),

To make the ears, Bonassar and colleagues started with a digitized 3-D image of a human subject’s ear and converted the image into a digitized “solid” ear using a 3-D printer to assemble a mold.

They injected the mold with collagen derived from rat tails, and then added 250 million cartilage cells from the ears of cows. This Cornell-developed, high-density gel is similar to the consistency of Jell-O when the mold is removed. The collagen served as a scaffold upon which cartilage could grow.

The process is also fast, Bonassar added: “It takes half a day to design the mold, a day or so to print it, 30 minutes to inject the gel, and we can remove the ear 15 minutes later. We trim the ear and then let it culture for several days in nourishing cell culture media before it is implanted.”

The incidence of microtia, which is when the external ear is not fully developed, varies from almost 1 to more than 4 per 10,000 births each year. Many children born with microtia have an intact inner ear, but experience hearing loss due to the missing external structure.

There was a show in 2004  at the Vancouver Art Gallery (Canada), Massive Change, curated by graphic designer Bruce Mau, which amongst many other objects and images featured a bioengineered nose being grown in a beaker. If memory serves, the work featuring the nose was from Israel and there was no mention of when that work might leave the lab and be used for implants. From the Chronicle article,

Bonassar and Spector have been collaborating on bioengineered human replacement parts since 2007. Bonassar has also worked with Weill Cornell neurological surgeon Dr. Roger Härtl on bioengineered disc replacements using some of the same techniques demonstrated in the PLOS One study.

The researchers specifically work on replacement human structures that are primarily made of cartilage — joints, trachea, spine, nose — because cartilage does not need to be vascularized with a blood supply in order to survive.

They are now looking at ways to expand populations of human ear cartilage cells in the laboratory so that these cells can be used in the mold, instead of cow cartilage.

“Using human cells, specifically those from the same patient, would reduce any possibility of rejection,” Spector said.

He added that the best time to implant a bioengineered ear on a child would be when they are about 5 or 6 years old. At that age, ears are 80 percent of their adult size.

If all future safety and efficacy tests work out, it might be possible to try the first human implant of a Cornell bioengineered ear in as little as three years, Spector said.

Good luck to them. For anyone who’s interested here’s a citation and link to the paper,

Reiffel AJ, Kafka C, Hernandez KA, Popa S, Perez JL, et al. (2013) High-Fidelity Tissue Engineering of Patient-Specific Auricles for Reconstruction of Pediatric Microtia and Other Auricular Deformities. PLoS ONE 8(2): e56506. doi:10.1371/journal.pone.0056506

PLoS One is an open access journal.

Phone up a kidney cell—scientists at ETH Zurich create a mammalian ‘cell phone’

The Sept. 17, 2012 news item on Nanowerk lays out the standard telephoning process, then applies it to mammalian cells (Note: I have removed a link),

Telephoning is a mutual exchange of information: A phones B and they both agree what B should do. Once this is done, Party B phones Party A to let him or her know. A no longer phones B. During this two-way communication, electrical signals are sent, and for their transmission suitable devices are necessary.

Based on this formula, a team of bioengineers headed by Martin Fussenegger and Jörg Stelling at ETH Zurich’s Department of Biosystems Science and Engineering in Basel has programmed mammalian cells in such a way that two cells can communicate via chemical signals (“Synthetic two-way communication between mammalian cells”).

Peter Ruegg’s Sept. 17, 2012 ETH Life article, (ETH is a science and technology university; in German: Eidgenössische Technische Hochschule Zürich) which originated the news item, outlines the research,

The researchers used suitable signal molecules and constructed “devices” out of biological components that receive, process and respond accordingly to the signals. The devices consist of suitable genes and their products, proteins, which are linked to each other logically.

An enzyme produces the amino acid L-tryptophan from indole, which has been introduced into the sender cell from outside. This little molecule enters the receiver cell, which processes the signal. The response to L-tryptophan is that the receiver produces acetaldehyde, which the sender cell can receive. If, after a certain time, a particular concentration of acetaldehyde has been attained or the indole is depleted, the sender cell stops producing L-tryptophan and the system switches itself off again.

Here are the specifics (from the Ruegg article),

For their experiment, the Basel-based researchers used so-called HEK cells – human kidney cells, in other words, which are often used in research. Moreover, the biological components necessary to construct the signal network can be used in a modular way. With these modules, the researchers were also able to connect other signal paths, including a signal cascade leading from the sender cell, through the information processing cell to the performing receiver cell without any feedback.

Thanks to their “cell phone”, the ETH-Zurich biotechnologists were able to simulate the latter accurately in a cell culture. They placed the sender and receiver module in the culture dish along with a population of endothelial cells, which line the blood-vessel walls. In response to the tryptophan signal, the receiver module formed the messenger VEGF [vascular endothelial growth factor, a signal protein] as well as acetaldehyde. This increases the permeability of the endothelial cells, which is a key prerequisite for blood-vessel growth.

Due to the acetaldehyde response, the sender module ultimately produced the signal molecule Ang1, which stops the permeability of the endothelial cells to inhibit blood-vessel growth.

At least one future application for this research is medical (from the Ruegg article),

This signal system is also found in the human body. If VEGF spirals out of control, however, too many blood vessels form, which ultimately feeds a growing tumour. The “cell phone” could therefore be a plausible strategy to halt the pathological formation of new blood vessels. “Communication is extremely important in controlling blood vessels,” says Fussenegger, “and we hope to be able to use synthetic ‘cell phones’ to correct or even cure disease-related cell communication systems precisely in the future with a ‘therapeutic call’.”

The scientists have found a way to illustrate their ‘cell phone’ research,

Researchers from ETH Zurich designed a “cell phone” made of biological components. A “therapeutical call” halts the pathological formation of new blood vessels. (Image: Andrea Lingk / ETH Zurich)

I have written for telecommunications companies and I think it’s safe to include my colleagues when I  say that neither I nor any of them imagined the possibility of making therapeutic calls to our cells.

Organ chips for DARPA (Defense Advanced Research Projects Agency)

The Wyss Institute will receive up to  $37M US for a project that integrates ten different organ-on-a-chip projects into one system. From the July 24, 2012 news release on EurekAlert,

With this new DARPA funding, Institute researchers and a multidisciplinary team of collaborators seek to build 10 different human organs-on-chips, to link them together to more closely mimic whole body physiology, and to engineer an automated instrument that will control fluid flow and cell viability while permitting real-time analysis of complex biochemical functions. As an accurate alternative to traditional animal testing models that often fail to predict human responses, this instrumented “human-on-a-chip” will be used to rapidly assess responses to new drug candidates, providing critical information on their safety and efficacy.

This unique platform could help ensure that safe and effective therapeutics are identified sooner, and ineffective or toxic ones are rejected early in the development process. As a result, the quality and quantity of new drugs moving successfully through the pipeline and into the clinic may be increased, regulatory decision-making could be better informed, and patient outcomes could be improved.

Jesse Goodman, FDA Chief Scientist and Deputy Commissioner for Science and Public Health, commented that the automated human-on-chip instrument being developed “has the potential to be a better model for determining human adverse responses. FDA looks forward to working with the Wyss Institute in its development of this model that may ultimately be used in therapeutic development.”

Wyss Founding Director, Donald Ingber, M.D., Ph.D., and Wyss Core Faculty member, Kevin Kit Parker, Ph.D., will co-lead this five-year project.

I note that Kevin Kit Parker was mentioned in an earlier posting today (July 26, 2012) titled, Medusa, jellyfish, and tissue engineering, and Donald Ingber in my Dec.1e, 2011 posting about Shrilk and insect skeletons.

As for the Wyss Institute, here’s a description from the news release,

The Wyss Institute for Biologically Inspired Engineering at Harvard University (http://wyss.harvard.edu) uses Nature’s design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world. Working as an alliance among Harvard’s Schools of Medicine, Engineering, and Arts & Sciences, and in partnership with Beth Israel Deaconess Medical Center, Boston Children’s Hospital, Brigham and Women’s Hospital, , Dana Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Tufts University, and Boston University, the Institute crosses disciplinary and institutional barriers to engage in high-risk research that leads to transformative technological breakthroughs. By emulating Nature’s principles for self-organizing and self-regulating, Wyss researchers are developing innovative new engineering solutions for healthcare, energy, architecture, robotics, and manufacturing. These technologies are translated into commercial products and therapies through collaborations with clinical investigators, corporate alliances, and new start-ups.

I hadn’t thought of an organ-on-a-chip as particularly bioinspired so I’ll have to think about that one for a while.