Tag Archives: Robert Langer

Tightening the skin (and protecting it and removing wrinkles, temporarily)

“It’s an invisible layer that can provide a barrier, provide cosmetic improvement, and potentially deliver a drug locally to the area that’s being treated. Those three things together could really make it ideal for use in humans,” Daniel Anderson says. Photo: Melanie Gonick/MIT

“It’s an invisible layer that can provide a barrier, provide cosmetic improvement, and potentially deliver a drug locally to the area that’s being treated. Those three things together could really make it ideal for use in humans,” Daniel Anderson says. Photo: Melanie Gonick/MIT

It almost looks like he’s peeling off his own skin and I imagine that’s the secret to this polymer’s success. A May 9, 2016 news item on phys.org describes the work being done at the Massachusetts Institute of Technology (MIT) and elsewhere with collaborators,

Scientists at MIT, Massachusetts General Hospital, Living Proof, and Olivo Labs have developed a new material that can temporarily protect and tighten skin, and smooth wrinkles. With further development, it could also be used to deliver drugs to help treat skin conditions such as eczema and other types of dermatitis.

A May 9, 2016 MIT news release (also on EurekAlert), which originated the news item, provides more detail,

The material, a silicone-based polymer that could be applied on the skin as a thin, imperceptible coating, mimics the mechanical and elastic properties of healthy, youthful skin. In tests with human subjects, the researchers found that the material was able to reshape “eye bags” under the lower eyelids and also enhance skin hydration. This type of “second skin” could also be adapted to provide long-lasting ultraviolet protection, the researchers say.

“It’s an invisible layer that can provide a barrier, provide cosmetic improvement, and potentially deliver a drug locally to the area that’s being treated. Those three things together could really make it ideal for use in humans,” says Daniel Anderson, an associate professor in MIT’s Department of Chemical Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES).

Anderson is one of the authors of a paper describing the polymer in the May 9 online issue of Nature Materials. Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute, is the paper’s senior author, and the paper’s lead author is Betty Yu SM ’98, ScD ’02, former vice president at Living Proof. Langer and Anderson are co-founders of Living Proof and Olivo Labs, and Yu earned her master’s and doctorate at MIT.

Mimicking skin

As skin ages, it becomes less firm and less elastic — problems that can be exacerbated by sun exposure. This impairs skin’s ability to protect against extreme temperatures, toxins, microorganisms, radiation, and injury. About 10 years ago, the research team set out to develop a protective coating that could restore the properties of healthy skin, for both medical and cosmetic applications.

“We started thinking about how we might be able to control the properties of skin by coating it with polymers that would impart beneficial effects,” Anderson says. “We also wanted it to be invisible and comfortable.”

The researchers created a library of more than 100 possible polymers, all of which contained a chemical structure known as siloxane — a chain of alternating atoms of silicon and oxygen. These polymers can be assembled into a network arrangement known as a cross-linked polymer layer (XPL). The researchers then tested the materials in search of one that would best mimic the appearance, strength, and elasticity of healthy skin.

“It has to have the right optical properties, otherwise it won’t look good, and it has to have the right mechanical properties, otherwise it won’t have the right strength and it won’t perform correctly,” Langer says.

The best-performing material has elastic properties very similar to those of skin. In laboratory tests, it easily returned to its original state after being stretched more than 250 percent (natural skin can be elongated about 180 percent). In laboratory tests, the novel XPL’s elasticity was much better than that of two other types of wound dressings now used on skin — silicone gel sheets and polyurethane films.

“Creating a material that behaves like skin is very difficult,” says Barbara Gilchrest, a dermatologist at MGH and an author of the paper. “Many people have tried to do this, and the materials that have been available up until this have not had the properties of being flexible, comfortable, nonirritating, and able to conform to the movement of the skin and return to its original shape.”

The XPL is currently delivered in a two-step process. First, polysiloxane components are applied to the skin, followed by a platinum catalyst that induces the polymer to form a strong cross-linked film that remains on the skin for up to 24 hours. This catalyst has to be added after the polymer is applied because after this step the material becomes too stiff to spread. Both layers are applied as creams or ointments, and once spread onto the skin, XPL becomes essentially invisible.

High performance

The researchers performed several studies in humans to test the material’s safety and effectiveness. In one study, the XPL was applied to the under-eye area where “eye bags” often form as skin ages. These eye bags are caused by protrusion of the fat pad underlying the skin of the lower lid. When the material was applied, it applied a steady compressive force that tightened the skin, an effect that lasted for about 24 hours.

In another study, the XPL was applied to forearm skin to test its elasticity. When the XPL-treated skin was distended with a suction cup, it returned to its original position faster than untreated skin.

The researchers also tested the material’s ability to prevent water loss from dry skin. Two hours after application, skin treated with the novel XPL suffered much less water loss than skin treated with a high-end commercial moisturizer. Skin coated with petrolatum was as effective as XPL in tests done two hours after treatment, but after 24 hours, skin treated with XPL had retained much more water. None of the study participants reported any irritation from wearing XPL.

“I think it has great potential for both cosmetic and noncosmetic applications, especially if you could incorporate antimicrobial agents or medications,” says Thahn Nga Tran, a dermatologist and instructor at Harvard Medical School, who was not involved in the research.

Living Proof has spun out the XPL technology to Olivo Laboratories, LLC, a new startup formed to focus on the further development of the XPL technology. Initially, Olivo’s team will focus on medical applications of the technology for treating skin conditions such as dermatitis.


This video supplied by MIT shows how to apply the polymer and offers a description and demonstration of its properties once applied,

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

An elastic second skin by Betty Yu, Soo-Young Kang, Ariya Akthakul, Nithin Ramadurai, Morgan Pilkenton, Alpesh Patel, Amir Nashat, Daniel G. Anderson, Fernanda H. Sakamoto, Barbara A. Gilchrest, R. Rox Anderson & Robert Langer. Nature Materials (2016) doi:10.1038/nmat4635 Published online 09 May 2016

This paper is behind a paywall.

One final comment, I wonder who’s lining up to invest in this product.

Nanomaterials and UV (ultraviolet) light for environmental cleanups

I think this is the first time I’ve seen anything about a technology that removes toxic materials from both water and soil; it’s usually one or the other. A July 22, 2015 news item on Nanowerk makes the announcement (Note: A link has been removed),

Many human-made pollutants in the environment resist degradation through natural processes, and disrupt hormonal and other systems in mammals and other animals. Removing these toxic materials — which include pesticides and endocrine disruptors such as bisphenol A (BPA) — with existing methods is often expensive and time-consuming.

In a new paper published this week in Nature Communications (“Nanoparticles with photoinduced precipitation for the extraction of pollutants from water and soil”), researchers from MIT [Massachusetts Institute of Technology] and the Federal University of Goiás in Brazil demonstrate a novel method for using nanoparticles and ultraviolet (UV) light to quickly isolate and extract a variety of contaminants from soil and water.

A July 21, 2015 MIT news release by Jonathan Mingle, which originated the news item, describes the inspiration and the research in more detail,

Ferdinand Brandl and Nicolas Bertrand, the two lead authors, are former postdocs in the laboratory of Robert Langer, the David H. Koch Institute Professor at MIT’s Koch Institute for Integrative Cancer Research. (Eliana Martins Lima, of the Federal University of Goiás, is the other co-author.) Both Brandl and Bertrand are trained as pharmacists, and describe their discovery as a happy accident: They initially sought to develop nanoparticles that could be used to deliver drugs to cancer cells.

Brandl had previously synthesized polymers that could be cleaved apart by exposure to UV light. But he and Bertrand came to question their suitability for drug delivery, since UV light can be damaging to tissue and cells, and doesn’t penetrate through the skin. When they learned that UV light was used to disinfect water in certain treatment plants, they began to ask a different question.

“We thought if they are already using UV light, maybe they could use our particles as well,” Brandl says. “Then we came up with the idea to use our particles to remove toxic chemicals, pollutants, or hormones from water, because we saw that the particles aggregate once you irradiate them with UV light.”

A trap for ‘water-fearing’ pollution

The researchers synthesized polymers from polyethylene glycol, a widely used compound found in laxatives, toothpaste, and eye drops and approved by the Food and Drug Administration as a food additive, and polylactic acid, a biodegradable plastic used in compostable cups and glassware.

Nanoparticles made from these polymers have a hydrophobic core and a hydrophilic shell. Due to molecular-scale forces, in a solution hydrophobic pollutant molecules move toward the hydrophobic nanoparticles, and adsorb onto their surface, where they effectively become “trapped.” This same phenomenon is at work when spaghetti sauce stains the surface of plastic containers, turning them red: In that case, both the plastic and the oil-based sauce are hydrophobic and interact together.

If left alone, these nanomaterials would remain suspended and dispersed evenly in water. But when exposed to UV light, the stabilizing outer shell of the particles is shed, and — now “enriched” by the pollutants — they form larger aggregates that can then be removed through filtration, sedimentation, or other methods.

The researchers used the method to extract phthalates, hormone-disrupting chemicals used to soften plastics, from wastewater; BPA, another endocrine-disrupting synthetic compound widely used in plastic bottles and other resinous consumer goods, from thermal printing paper samples; and polycyclic aromatic hydrocarbons, carcinogenic compounds formed from incomplete combustion of fuels, from contaminated soil.

The process is irreversible and the polymers are biodegradable, minimizing the risks of leaving toxic secondary products to persist in, say, a body of water. “Once they switch to this macro situation where they’re big clumps,” Bertrand says, “you won’t be able to bring them back to the nano state again.”

The fundamental breakthrough, according to the researchers, was confirming that small molecules do indeed adsorb passively onto the surface of nanoparticles.

“To the best of our knowledge, it is the first time that the interactions of small molecules with pre-formed nanoparticles can be directly measured,” they write in Nature Communications.

Nano cleansing

Even more exciting, they say, is the wide range of potential uses, from environmental remediation to medical analysis.

The polymers are synthesized at room temperature, and don’t need to be specially prepared to target specific compounds; they are broadly applicable to all kinds of hydrophobic chemicals and molecules.

“The interactions we exploit to remove the pollutants are non-specific,” Brandl says. “We can remove hormones, BPA, and pesticides that are all present in the same sample, and we can do this in one step.”

And the nanoparticles’ high surface-area-to-volume ratio means that only a small amount is needed to remove a relatively large quantity of pollutants. The technique could thus offer potential for the cost-effective cleanup of contaminated water and soil on a wider scale.

“From the applied perspective, we showed in a system that the adsorption of small molecules on the surface of the nanoparticles can be used for extraction of any kind,” Bertrand says. “It opens the door for many other applications down the line.”

This approach could possibly be further developed, he speculates, to replace the widespread use of organic solvents for everything from decaffeinating coffee to making paint thinners. Bertrand cites DDT, banned for use as a pesticide in the U.S. since 1972 but still widely used in other parts of the world, as another example of a persistent pollutant that could potentially be remediated using these nanomaterials. “And for analytical applications where you don’t need as much volume to purify or concentrate, this might be interesting,” Bertrand says, offering the example of a cheap testing kit for urine analysis of medical patients.

The study also suggests the broader potential for adapting nanoscale drug-delivery techniques developed for use in environmental remediation.

“That we can apply some of the highly sophisticated, high-precision tools developed for the pharmaceutical industry, and now look at the use of these technologies in broader terms, is phenomenal,” says Frank Gu, an assistant professor of chemical engineering at the University of Waterloo in Canada, and an expert in nanoengineering for health care and medical applications.

“When you think about field deployment, that’s far down the road, but this paper offers a really exciting opportunity to crack a problem that is persistently present,” says Gu, who was not involved in the research. “If you take the normal conventional civil engineering or chemical engineering approach to treating it, it just won’t touch it. That’s where the most exciting part is.”

The researchers have made this illustration of their work available,

Nanoparticles that lose their stability upon irradiation with light have been designed to extract endocrine disruptors, pesticides, and other contaminants from water and soils. The system exploits the large surface-to-volume ratio of nanoparticles, while the photoinduced precipitation ensures nanomaterials are not released in the environment. Image: Nicolas Bertrand Courtesy: MIT

Nanoparticles that lose their stability upon irradiation with light have been designed to extract endocrine disruptors, pesticides, and other contaminants from water and soils. The system exploits the large surface-to-volume ratio of nanoparticles, while the photoinduced precipitation ensures nanomaterials are not released in the environment.
Image: Nicolas Bertrand Courtesy: MIT

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

Nanoparticles with photoinduced precipitation for the extraction of pollutants from water and soil by Ferdinand Brandl, Nicolas Bertrand, Eliana Martins Lima & Robert Langer. Nature Communications 6, Article number: 7765 doi:10.1038/ncomms8765 Published 21 July 2015

This paper is open access.

Inspired by babies, scientists consider* popping nanoparticle pills and downing nanoparticle potions

Given the choice over injections or suppositories most of us will choose to take medication orally (pills or liquids). It may be a surprise to some but with all the talk about nanomedicine there has been a problem with using nanoparticles in an oral delivery system which scientists at the Brigham and Women’s Hospital (BWH) and Massachusetts Institute of Technology (MIT) have solved. From a Nov. 27, 2013 BWH news release, on EurekAlert,

… a study led by researchers at Brigham and Women’s Hospital (BWH) and Massachusetts Institute of Technology (MIT) is the first to report in the field of nanomedicine a new type of nanoparticle that can be successfully absorbed through the digestive tract. The findings may one day allow patients to simply take a pill instead of receiving injections.

Until recently, after being injected into the body, nanoparticles travelled to their destination, such as a tumor, by seeping through leaky vessels. The research team, led by Farokhzad [Omid Farokhzad, MD, director of the BWH Laboratory of Nanomedicine and Biomaterials, senior study author] and Robert Langer, ScD of MIT, developed nanoparticles that could reach the target site without relying on injection nor leaky vessels.

For nanoparticles to be taken orally they need to cross the intestinal lining. This lining is composed of a layer of epithelial cells joined together to form impenetrable barriers called tight junctions. To ensure that the nanoparticles could cross these barriers, the researchers took a cue from research on how babies absorb antibodies from their mothers’ milk. The antibodies would grab onto a receptor, known as neonatal Fc receptors, found on the cell surface. This gave them access across the cells of the intestinal lining into neighboring blood vessels.

Based on this knowledge, the researchers decorated nanoparticles with Fc proteins that targeted and bound to these receptors, which are also found in adult intestinal cells. After attaching to the receptors, the Fc-protein-decorated nanoparticles—toting their drug payload—are all absorbed into the intestinal lining and into the bloodstream at a high concentration.

According to the researchers, these receptors can be used to transport nanoparticles carrying different kinds of drugs and other materials—a feat that combines a versatile vehicle and an easily accessible passageway across cellular barriers.

To demonstrate how transport of Fc-targeted nanoparticles could impact the clinical space, the researchers focused on a diabetes treatment scenario, showing how oral delivery of insulin via these targeted nanoparticles could alter blood sugar levels in mice.

Insulin carried in nanoparticles decorated with Fc proteins reached the bloodstream more efficiently than those without the proteins. Moreover, the amount of insulin delivered was large enough to lower the mice’s blood sugar levels. Aside from insulin, the researchers note that the nanoparticles can be used to carry any kind of drug to treat many diseases.

“Being able to deliver nanomedicine orally would offer clinicians broad and novel ways to treat today’s many chronic diseases that require daily therapy, such as diabetes and cancer,” said Langer. “Imagine being able to take RNA or proteins orally; that would be paradigm shift.”

In terms of next steps, the researchers are working to enhance the nanoparticles’ drug-releasing abilities to prepare for future pre-clinical testing with insulin and other drugs. They also plan to design nanoparticles that can cross other barriers, such as the blood-brain barrier, which prevents many drugs from reaching the brain.

The Nov. 27, 2013 MIT news release by Anne Trafton on EurekAlert provides additional insight into the difficulties of getting nanoparticles past our digestive tracts (this is a bit repetitive but there’s enough new detail to make it worth my while to include it here),,

Several types of nanoparticles carrying chemotherapy drugs or short interfering RNA, which can turn off selected genes, are now in clinical trials to treat cancer and other diseases. These particles exploit the fact that tumors and other diseased tissues are surrounded by leaky blood vessels. After the particles are intravenously injected into patients, they seep through those leaky vessels and release their payload at the tumor site.

For nanoparticles to be taken orally, they need to be able to get through the intestinal lining, which is made of a layer of epithelial cells that join together to form impenetrable barriers called tight junctions.

“The key challenge is how to make a nanoparticle get through this barrier of cells. Whenever cells want to form a barrier, they make these attachments from cell to cell, analogous to a brick wall where the bricks are the cells and the mortar is the attachments, and nothing can penetrate that wall,” Farokhzad says.

Researchers have previously tried to break through this wall by temporarily disrupting the tight junctions, allowing drugs through. However, this approach can have unwanted side effects because when the barriers are broken, harmful bacteria can also get through.

To build nanoparticles that can selectively break through the barrier, the researchers took advantage of previous work that revealed how babies absorb antibodies from their mothers’ milk, boosting their own immune defenses. Those antibodies grab onto a cell surface receptor called the FcRN, granting them access through the cells of the intestinal lining into adjacent blood vessels.

The researchers coated their nanoparticles with Fc proteins — the part of the antibody that binds to the FcRN receptor, which is also found in adult intestinal cells. The nanoparticles, made of a biocompatible polymer called PLA-PEG, can carry a large drug payload, such as insulin, in their core.

After the particles are ingested, the Fc proteins grab on to the FcRN in the intestinal lining and gain entry, bringing the entire nanoparticle along with them.

“It illustrates a very general concept where we can use these receptors to traffic nanoparticles that could contain pretty much anything. Any molecule that has difficulty crossing the barrier could be loaded in the nanoparticle and trafficked across,” Karnik [Rohit Karnik, an MIT associate professor of mechanical engineering] says.

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

Transepithelial Transport of Fc-Targeted Nanoparticles by the Neonatal Fc Receptor for Oral Delivery by Eric M. Pridgen, Frank Alexis, Timothy T. Kuo, Etgar Levy-Nissenbaum, Rohit Karnik, Richard S. Blumberg, Robert Langer, and Omid C. Farokhzad.
Sci Transl Med 27 November 2013: Vol. 5, Issue 213, p. 213ra167 DOI: 10.1126/scitranslmed.3007049

This article is behind a paywall.

*  ‘consdier’ corrected to ‘consider’ on June 5, 2014.

Russia’s nanotechnology efforts falter?

The title for Leonid Bershidksy’s May 16, 2013 Bloomberg.com article, Power Grab Trumps Nanotechnology in Putin’s Russia, casts an ominous shadow over Rusnano’s situation (Note: Links have been removed),

The projects, known as Rusnano and Skolkovo, were meant to propel Russia’s raw-material economy into the technology age. They involved multibillion-dollar government investments, the first in nanotechnology and the second in a new city that would become Russia’s answer to Silicon Valley. They were supposed to provide the infrastructure and stability required to attract large amounts of foreign investment.

Now, both have become targets in Putin’s campaign to demonstrate that he’s being tough on corruption and mismanagement of government funds. As a result, their chances of succeeding are looking increasingly remote.

Trouble came in April [2013], when the Accounting Chamber, a body charged with auditing government spending, accused Rusnano of inefficient management in a report that received ample coverage on state-owned TV. It said that Rusnano had transferred about $40 million to shell companies and pointed out that a silicon factory in which Rusnano invested about $450 million was not functioning and was about to be declared insolvent. The report also highlighted the state company’s 2012 losses of 2.5 billion rubles ($80 million) and the 24.4-billion-ruble (about $800 million) in reserves Rusnano had formed against potential losses from risky ventures.

Anatoly Medetsky’s Apr. 29, 2013 article for The Moscow Times provides more insight into the situation,

The government’s Audit Chamber on Friday [April 26, 2013] accused state-owned Rusnano of multiple infractions in a blow to the high-tech corporation’s chief, Anatoly Chubais.

The chamber’s critical conclusions followed President Vladimir Putin’s reproof of the company during a live call-in show the previous day.

Auditors made their statement after examining Rusnano’s records in response to a request by Chubais’ political nemesis, the Communist Party.

“The audit’s materials attest that Rusnano’s performance was inappropriate to attain the goals that it was entrusted with, which are the development of the national nano industry,” the Audit Chamber said in a statement.

Auditor Sergei Agaptsov said separately that Rusnano is unlikely to achieve the goal of 300 billion rubles in annual sales of nano-tech products by the companies it co-owns in 2015 — the target that the government set for the company, Interfax reported.

I’m sorry to read about Rusnano’s difficulties especially in light my first piece about it where I compared the Canadian effort unfavourably to, what was then, a relatively new and promising organization in my Apr. 14, 2009 posting. About seventeen months later, officials with Rusnano signed a memorandum of understanding with John Varghese, CEO and Managing Partner of Toronto based venture capital firm, VentureLink Funds as noted in my Sept. 14, 2010 posting. Nothing further seemed to come of that agreement.

I have one last thought about Rusnano’s current travails, will they have an impact on US commercialization efforts? In my Oct. 28, 2011 posting where I was contrasting nanotechnology commercialization efforts by the US, Spain, and Rusnano, I mentioned this deal Rusnano had made with two US nanomedicine companies,

Then RUSNANO announced its investments in Selecta Biosciences and BIND Biosiences, from the Oct. 27, 2011 news item on Nanowerk,

BIND Biosciences and Selecta Biosciences, two leading nanomedicine companies, announced today that they have entered into investment agreements with RUSNANO, a $10-billion Russian Federation fund that supports high-tech and nanotechnology advances. [emphasis mine]

RUSNANO is co-investing $25 million in BIND and $25 million in Selecta, for a total RUSNANO investment of $50 million within the total financing rounds of $94.5 million in the two companies combined. …

The proprietary technology platforms of BIND and Selecta originated in laboratories at Harvard Medical School directed by Professor Omid Farokhzad, MD, and in laboratories at MIT directed by Professor Robert Langer, ScD, a renowned scientist who is a recipient of the US National Medal of Science, the highest US honor for scientists, and is an inventor of approximately 850 patents issued or pending worldwide. Drs. Langer and Farokhzad are founders of both companies.

Ripple effects, eh? Rusnano was very active internationally.

ETA June 14, 2013:  Nanowerk has a June 13, 2013 news item, which updates the situation with the news that Rusnano has opted out of presenting an ‘initial public offering’, aka, listing itself on a stock exchange in 2015 and will instead attract private investment.

Evolution is the best problem-solver

Dr. Jeffrey Karp of Brigham and Women’s Hospital says, “I truly believe evolution is the best problem-solver,” when discussing his medical biomimcry work in this video,

You can find the video and more in a Mar. 20, 2013 news item on Nanowerk which was originated by a Mar. 6, 2013 article by Alisa Zapp Machalek for the US National Institutes of Health (NIH) National Institute of General Medical Sciences (NGMS) Inside Life Science webpage,

Velcro® was inspired by the grappling hooks of burrs. Supersonic jets have structures that work like the nostrils of peregrine falcons in a speed dive. Full-body swimsuits, now banned from the Olympics, lend athletes a smooth, streamlined shape like fish.

Nature’s designs are also giving researchers funded by the National Institutes of Health ideas for new technologies that could help wounds heal, make injections less painful and provide new materials for a variety of purposes.

… scientists [Jeffrey Karp and Robert Langer] discovered, to their surprise, that a [porcupine] quill’s puncture power comes from its barbed tip. Barbs seem to work like the points on a serrated knife, concentrating pressure onto small areas to aid penetration. Because they require significantly less force to puncture skin, barbed shafts don’t hurt as much when they enter flesh as their smooth-tipped counterparts do.

Zapp Machalek goes on to detail work inspired by gecko feet and spider webs, as well as, porcupine quills.

Forbes magazine and US science culture

Forbes magazine, which is based in the US but now has editions produced in many countries, describes its focus as business and finance. So, it might seem a little unexpected to find a list of rising stars in the fields of science and health until one remembers the current fascination, worldwide, with innovation which often seems to mean science research which can be commercialized.

Forbes has just published its list of ’30 under 30′ rising stars in the fields of Science and Health Care. Pedro Valencia, who studied with and worked in Robert Langer’s lab at the Massachusetts Institute of Technology (MIT), was one of the 30 cited in the 2012 list. From the Dec. 27, 2012 news item on Azonano,

Valencia was cited for figuring out “how to more quickly synthesize nanoparticles that can be used to make drugs more effective and less toxic and to put multiple drugs inside the same nanotech medicine. This has resulted in many top-notch scientific publications and the formation of a start-up, Blend Therapeutics.”

Valencia was the recipient of the NSF Graduate Fellowship. He was co-advised by Professor Langer and Dr. Omid Farokhzad of the Brigham Women’s Hospital – Harvard Medical School.

Langer and Farokhzad were mentioned in my Oct. 28, 2011 posting about nanotechnology commercialization efforts,

… BIND Biosciences and Selecta Biosciences, two leading nanomedicine companies, announced today that they have entered into investment agreements with RUSNANO, a $10-billion Russian Federation fund that supports high-tech and nanotechnology advances.

RUSNANO is co-investing $25 million in BIND and $25 million in Selecta, for a total RUSNANO investment of $50 million within the total financing rounds of $94.5 million in the two companies combined. …

The proprietary technology platforms of BIND and Selecta originated in laboratories at Harvard Medical School directed by Professor Omid Farokhzad, MD, and in laboratories at MIT directed by Professor Robert Langer, ScD, a renowned scientist who is a recipient of the US National Medal of Science, the highest US honor for scientists, and is an inventor of approximately 850 patents issued or pending worldwide. Drs. Langer and Farokhzad are founders of both companies. [Farokhzad was featured in a recent Canadian Broadcasting Corporation {CBC}, Nature of Things, television episode about nanomedicine, titled More than human.] Professor Ulrich von Andrian, MD, PhD, head of the immunopathology laboratory at Harvard Medical School, is a founder of Selecta.

It is fascinating to observe not only the linkages between business and science/health but also the way in which those linkages contribute to a larger ‘science culture’, which includes science festivals, science-oriented popular culture, science talks for just a few examples.

Gluing blood vessels with mussel goo

The University of British Columbia [UBC] Dec. 11, 2012 news release states,

A University of British Columbia researcher has helped create a gel – based on the mussel’s knack for clinging to rocks, piers and boat hulls – that can be painted onto the walls of blood vessels and stay put, forming a protective barrier with potentially life-saving implications.

Co-invented by Assistant Professor Christian Kastrup while a postdoctoral student at the Massachusetts Institute of Technology, the gel is similar to the amino acid that enables mussels to resist the power of churning water. The variant that Kastrup and his collaborators created, described in the current issue of the online journal PNAS [Proceeings of the National Academy of Sciences of the US] Early Edition, can withstand the flow of blood through arteries and veins.

Here’s the citation and a link to the article (which is behind a paywall),

Painting blood vessels and atherosclerotic plaques with an adhesive drug depot by Christian J. Kastrup, Matthias Nahrendorf, Jose Luiz Figueiredo, Haeshin Lee, Swetha Kambhampati, Timothy Lee, Seung-Woo Cho, Rostic Gorbatov, Yoshiko Iwamoto, Tram T. Dang, Partha Dutta, Ju Hun Yeon, Hao Cheng, Christopher D. Pritchard, Arturo J. Vegas, Cory D. Siegel, Samantha MacDougall, Michael Okonkwo, Anh Thai, James R. Stone, Arthur J. Coury, Ralph Weissleder, Robert Langer, and Daniel G. Anderson.  PNAS, December 11, 2012 DOI: 10.1073/pnas.1217972110

For those of a more technical turn of mind, here’s the abstract (from PNAS),

The treatment of diseased vasculature remains challenging, in part because of the difficulty in implanting drug-eluting devices without subjecting vessels to damaging mechanical forces. Implanting materials using adhesive forces could overcome this challenge, but materials have previously not been shown to durably adhere to intact endothelium under blood flow. Marine mussels secrete strong underwater adhesives that have been mimicked in synthetic systems. Here we develop a drug-eluting bioadhesive gel that can be locally and durably glued onto the inside surface of blood vessels. In a mouse model of atherosclerosis, inflamed plaques treated with steroid-eluting adhesive gels had reduced macrophage content and developed protective fibrous caps covering the plaque core. Treatment also lowered plasma cytokine levels and biomarkers of inflammation in the plaque. The drug-eluting devices developed here provide a general strategy for implanting therapeutics in the vasculature using adhesive forces and could potentially be used to stabilize rupture-prone plaques.

The news release describes the work layperson’s terms,

The gel’s “sheer strength” could shore up weakened vessel walls at risk of rupturing – much like the way putty can fill in dents in a wall, says Kastrup, a member of the Department of Biochemistry and Molecular Biology and the Michael Smith Laboratories.

By forming a stable barrier between blood and the vessel walls, the gel could also prevent the inflammation that typically occurs when a stent is inserted to widen a narrowed artery or vein; that inflammation often counteracts the opening of the vessel that the stent was intended to achieve.

The widest potential application would be preventing the rupture of blood vessel plaque. When a plaque ruptures, the resulting clot can block blood flow to the heart (triggering a heart attack) or the brain (triggering a stroke). Mice treated with a combination of the gel and an anti-inflammatory steroid had more stable plaque than a control group of untreated mice.

“By mimicking the mussel’s ability to cling to objects, we created a substance that stays in place in a very dynamic environment with high flow velocities,” says Kastrup, a member of UBC’s Centre for Blood Research.

Robert Langer, one of the paper’s co-authors, was mentioned here in an Aug. 27, 2012 posting about nanoelectronics, tissue engineering, and medicine.

Medicine, nanoelectronics, social implications, and figuring it all out

Given today’s (Aug. 27, 2012) earlier posting about nanoelectronics and tissue engineering, I though it was finally time to feature Michael Berger’s Aug. 16, 2012 Nanowerk Spotlight essay, The future of nanotechnology electronics in medicine, which discusses the integration of electronics into the human body.

First, Berger offers a summary of some of the latest research (Note: I have removed  links),

In previous Nanowerk Spotlights we have already covered numerous research advances in this area: The development of a nanobioelectronic system that triggers enzyme activity and, in a similar vein, the electrically triggered drug release from smart nanomembranes; an artificial retina for color vision; nanomaterial-based breathalyzers as diagnostic tools; nanogenerators to power self-sustained biosystems and implants; future bio-nanotechnology might even use computer chips inside living cells.

A lot of nanotechnology work is going on in the area of brain research. For instance the use of a carbon nanotube rope to electrically stimlate neural stem cells; nanotechnology to repair the brain and other advances in fabricating nanomaterial-neural interfaces for signal generation.

International cooperation in this field has also picked up. Just recently, scientists have formed a global alliance for nanobioelectronics to rapidly find solutions for neurological disorders; the EuroNanoBio project is a Support Action funded under the 7th Framework Programme of the European Union; and ENIAC, the European Technology Platform on nanoelectronics, has decided to make the development of medical applications one of its main objectives.

Berger cites a recent article in the American Chemical Society’s (ACS) Nano (journal) by scientists in today’s earlier posting about tissue scaffolding and 3-D electrnonics,

In a new perspective article in the July 31, 2012, online edition of ACS Nano (“The Smartest Materials: The Future of Nanoelectronics in Medicine” [behind a paywall]), Tzahi Cohen-Karni (a researcher in Kohane’s lab), Robert Langer, and Daniel S. Kohane provide an overview of nanoelectronics’ potential in the biomedical sciences.

They write that, as with many other areas of scientific endeavor in recent decades, continued progress will require the convergence of multiple disciplines, including chemistry, biology, electrical engineering, computer science, optics, material science, drug delivery, and numerous medical disciplines. ”

Advances in this research could lead to extremely sophisticated smart materials with multifunctional capabilities that are built in – literally hard-wired. The impact of this research could cover the spectrum of biomedical possibilities from diagnostic studies to the creation of cyborgs.”

Berger finishes with this thought,

Ultimately, and here we are getting almost into science fiction territory, nanostructures could not only incorporate sensing and stimulating capabilities but also potentially introduce computational capabilities and energy-generating elements. “In this way, one could fabricate a truly independent system that senses and analyzes signals, initiates interventions, and is self-sustained. Future developments in this direction could, for example, lead to a synthetic nanoelectronic autonomic nervous system.”

This Nanowerk Spotlight essay provides a good overview of nanoelectronics  research in medicine and lots of  links to previous related essays and other related materials.

I am intrigued that there is no mention of the social implications for this research and I find social science or humanities research on social social implications of emerging technology rarely discusses the technical aspects revealing what seems to be an insurmountable gulf. I suppose that’s why we need writers, artists, musicians, dancers, pop culture, and the like to create experiences, installations, and narratives that help us examine the technologies and their social implications, up close.

The body as an electronic device—adding electronics to biological tissue

What makes this particular combination of electronic s  and living tissue special is t that it was achieved in 3-D rather than 2-D.  From the Boston Children’s Hospital Aug. 26, 2012 news release on EurekAlert,

A multi-institutional research team has developed a method for embedding networks of biocompatible nanoscale wires within engineered tissues. These networks—which mark the first time that electronics and tissue have been truly merged in 3D—allow direct tissue sensing and potentially stimulation, a potential boon for development of engineered tissues that incorporate capabilities for monitoring and stimulation, and of devices for screening new drugs.

The Aug. 27, 2012 news item on Nanowerk provides more detail about integration of the cells and electronics,

Until now, the only cellular platforms that incorporated electronic sensors consisted of flat layers of cells grown on planar metal electrodes or transistors. Those two-dimensional systems do not accurately replicate natural tissue, so the research team set out to design a 3-D scaffold that could monitor electrical activity, allowing them to see how cells inside the structure would respond to specific drugs.

The researchers built their new scaffold out of epoxy, a nontoxic material that can take on a porous, 3-D structure. Silicon nanowires embedded in the scaffold carry electrical signals to and from cells grown within the structure.

“The scaffold is not just a mechanical support for cells, it contains multiple sensors. We seed cells into the scaffold and eventually it becomes a 3-D engineered tissue,” Tian says [Bozhi Tian, a former postdoc at MIT {Massachusetts Institute of Technology} and Children’s Hospital and a lead author of the paper ].

The team chose silicon nanowires for electronic sensors because they are small, stable, can be safely implanted into living tissue and are more electrically sensitive than metal electrodes. The nanowires, which range in diameter from 30 to 80 nanometers (about 1,000 times smaller than a human hair), can detect voltages less than one-thousandth of a watt, which is the level of electricity that might be seen in a cell.

Here’s more about why the researchers want to integrate living tissue and electronics, from the Harvard University Aug. 26, 2012 news release on EurekAlert,

“The current methods we have for monitoring or interacting with living systems are limited,” said Lieber [Charles M. Lieber, the Mark Hyman, Jr. Professor of Chemistry at Harvard and one of the study’s team leaders]. “We can use electrodes to measure activity in cells or tissue, but that damages them. With this technology, for the first time, we can work at the same scale as the unit of biological system without interrupting it. Ultimately, this is about merging tissue with electronics in a way that it becomes difficult to determine where the tissue ends and the electronics begin.”

The research addresses a concern that has long been associated with work on bioengineered tissue – how to create systems capable of sensing chemical or electrical changes in the tissue after it has been grown and implanted. The system might also represent a solution to researchers’ struggles in developing methods to directly stimulate engineered tissues and measure cellular reactions.

“In the body, the autonomic nervous system keeps track of pH, chemistry, oxygen and other factors, and triggers responses as needed,” Kohane [Daniel Kohane, a Harvard Medical School professor in the Department of Anesthesia at Children’s Hospital Boston and a team leader] explained. “We need to be able to mimic the kind of intrinsic feedback loops the body has evolved in order to maintain fine control at the cellular and tissue level.”

Here’s a citation and a link to the paper (which is behind a paywall),

Macroporous nanowire nanoelectronic scaffolds for synthetic tissues by Bozhi Tian, Jia Lin, Tal Dvir, Lihua Jin, Jonathan H. Tsui, Quan  Qing, Zhigang Suo, Robert Langer, Daniel S. Kohane, and Charles M. Lieber in Nature Materials (2012) doi:10.1038/nmat3404 Published onlin26 August 2012.

This is the image MIT included with its Aug 27, 2012 news release (which originated the news item on Nanowerk),

A 3-D reconstructed confocal fluorescence micrograph of a tissue scaffold.
Image: Charles M. Lieber and Daniel S. Kohane.

At this point they’re discussing therapeutic possibilities but I expect that ‘enhancement’ is also being considered although not mentioned for public consumption.