Tag Archives: Scaffold

Shape-conforming hydrogel and the body’s own healing mechanisms

A June 11, 2018 news item on ScienceDaily announces a development of interest to people with diabetes or those who treat them,

A simple scrape or sore might not cause alarm for most people. But for diabetic patients, an untreated scratch can turn into an open wound that could potentially lead to a limb amputation or even death.

A Northwestern University team has developed a new device, called a regenerative bandage, that quickly heals these painful, hard-to-treat sores without using drugs. During head-to-head tests, Northwestern’s bandage healed diabetic wounds 33 percent faster than one of the most popular bandages currently on the market.

A June 11, 2018 Northwestern University news release by Amanda Morris, which originated the news item, provides more detail,

“The novelty is that we identified a segment of a protein in skin that is important to wound healing, made the segment and incorporated it into an antioxidant molecule that self-aggregates at body temperature to create a scaffold that facilitates the body’s ability to regenerate tissue at the wound site,” said Northwestern’s Guillermo Ameer, who led the study. “With this newer approach, we’re not releasing drugs or outside factors to accelerate healing. And it works very well.”

Because the bandage leverages the body’s own healing power without releasing drugs or biologics, it faces fewer regulatory hurdles. This means patients could see it on the market much sooner.

The research was published today, June 11 [2018], in the Proceedings of the National Academy of Sciences. Although Ameer’s laboratory is specifically interested in diabetes applications, the bandage can be used to heal all types of open wounds.

An expert in biomaterials and regenerative engineering, Ameer is the Daniel Hale Williams Professor of Biomedical Engineering in the McCormick School of Engineering, professor of surgery in the Feinberg School of Medicine and director of Northwestern’s new Center for Advanced Regenerative Engineering (CARE).

The difference between a sore in a physically healthy person versus a diabetic patient? Diabetes can cause nerve damage that leads to numbness in the extremities. People with diabetes, therefore, might experience something as simple as a blister or small scratch that goes unnoticed and untreated because they cannot feel it to know it’s there. As high glucose levels also thicken capillary walls, blood circulation slows, making it more difficult for these wounds to heal. It’s a perfect storm for a small nick to become a limb-threatening — or life-threatening — wound.

The secret behind Ameer’s regenerative bandage is laminin, a protein found in most of the body’s tissues including the skin. Laminin sends signals to cells, encouraging them to differentiate, migrate and adhere to one another. Ameer’s team identified a segment of laminin — 12 amino acids in length — called A5G81 that is critical for the wound-healing process.

“This particular sequence caught our eye because it activates cellular receptors to get cells to adhere, migrate and proliferate,” Ameer said. “Then we cut up the sequence to find the minimum size that we needed for it to work.”

By using such a small fragment of laminin rather than the entire protein, it can be easily synthesized in the laboratory — making it more reproducible while keeping manufacturing costs low. Ameer’s team incorporated A5G81 into an antioxidant hydrogel bandage that it previously developed in the laboratory.

The bandage’s antioxidant nature counters inflammation. And the hydrogel is thermally responsive: It is a liquid when applied to the wound bed, then rapidly solidifies into a gel when exposed to body temperature. This phase change allows it to conform to the exact shape of the wound — a property that helped it out-perform other bandages on the market.

“Wounds have irregular shapes and depths. Our liquid can fill any shape and then stay in place,” Ameer said. “Other bandages are mostly based on collagen films or sponges that can move around and shift away from the wound site.”

Patients also must change bandages often, which can rip off the healing tissue and re-injure the site. Ameer’s bandage, however, can be rinsed off with cool saline, so the regenerating tissue remains undisturbed.

Not only will the lack of drugs or biologics make the bandage move to market faster, it also increases the bandage’s safety. So far, Ameer’s team has not noticed any adverse side effects in animal models. This is a stark difference from another product on the market, which contains a growth factor linked to cancer.

“It is not acceptable for patients who are trying to heal an open sore to have to deal with an increased risk of cancer,” Ameer said.

Next, Ameer’s team will continue to investigate the bandage in a larger pre-clinical model.

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

Potent laminin-inspired antioxidant regenerative dressing accelerates wound healing in diabetes by Yunxiao Zhu, Zdravka Cankova, Marta Iwanaszko, Sheridan Lichtor, Milan Mrksich, and Guillermo A. Ameer. PNAS [Proceedings of the National Academy of Science] June 11, 2018. 201804262; published ahead of print June 11, 2018. https://doi.org/10.1073/pnas.1804262115

This paper is behind a paywall.

Sugar in your bones might be better for you than you think

These days sugar is often  viewed as leading to health problems but there is an instance where it may be useful—bone regeneration. From a June 19, 2017 news item on Nanowerk (Note: A link has been removed),

There hasn’t been a gold standard for how orthopaedic spine surgeons promote new bone growth in patients, but now Northwestern University scientists have designed a bioactive nanomaterial that is so good at stimulating bone regeneration it could become the method surgeons prefer.

While studied in an animal model of spinal fusion, the method for promoting new bone growth could translate readily to humans, the researchers say, where an aging but active population in the U.S. is increasingly receiving this surgery to treat pain due to disc degeneration, trauma and other back problems. Many other procedures could benefit from the nanomaterial, ranging from repair of bone trauma to treatment of bone cancer to bone growth for dental implants.

“Regenerative medicine can improve quality of life by offering less invasive and more successful approaches to promoting bone growth,” said Samuel I. Stupp, who developed the new nanomaterial. “Our method is very flexible and could be adapted for the regeneration of other tissues, including muscle, tendons and cartilage.”

Stupp is director of Northwestern’s Simpson Querrey Institute for BioNanotechnology and the Board of Trustees Professor of Materials Science and Engineering, Chemistry, Medicine and Biomedical Engineering.

For the interdisciplinary study, Stupp collaborated with Dr. Wellington K. Hsu, associate professor of orthopaedic surgery, and Erin L. K. Hsu, research assistant professor of orthopaedic surgery, both at Northwestern University Feinberg School of Medicine. The husband-and-wife team is working to improve clinically employed methods of bone regeneration.

Sugar molecules on the surface of the nanomaterial provide its regenerative power. The researchers studied in vivo the effect of the “sugar-coated” nanomaterial on the activity of a clinically used growth factor, called bone morphogenetic protein 2 (BMP-2). They found the amount of protein needed for a successful spinal fusion was reduced to an unprecedented level: 100 times less of BMP-2 was needed. This is very good news, because the growth factor is known to cause dangerous side effects when used in the amounts required to regenerate high-quality bone, and it is expensive as well.

A June 19, 2017 Northwestern University news release by Megan Fellman, which originated the news item, tells the rest of the story,

Stupp’s biodegradable nanomaterial functions as an artificial extracellular matrix, which mimics what cells in the body usually interact with in their surroundings. BMP-2 activates certain types of stem cells and signals them to become bone cells. The Northwestern matrix, which consists of tiny nanoscale filaments, binds the protein by molecular design in the way that natural sugars bind it in our bodies and then slowly releases it when needed, instead of in one early burst, which can contribute to side effects.

To create the nanostructures, the research team led by Stupp synthesized a specific type of sugar that closely resembles those used by nature to activate BMP-2 when cell signaling is necessary for bone growth. Rapidly moving flexible sugar molecules displayed on the surface of the nanostructures “grab” the protein in a specific spot that is precisely the same one used in biological systems when it is time to deploy the signal. This potentiates the bone-growing signals to a surprising level that surpasses even the naturally occurring sugar polymers in our bodies.

In nature, the sugar polymers are known as sulfated polysaccharides, which have super-complex structures impossible to synthesize at the present time with chemical techniques. Hundreds of proteins in biological systems are known to have specific domains to bind these sugar polymers in order to activate signals. Such proteins include those involved in the growth of blood vessels, cell recruitment and cell proliferation, all very important biologically in tissue regeneration. Therefore, the approach of the Stupp team could be extended to other regenerative targets.

Spinal fusion is a common surgical procedure that joins adjacent vertebra together using a bone graft and growth factors to promote new bone growth, which stabilizes the spine. The bone used in the graft can come from the patient’s pelvis — an invasive procedure — or from a bone bank.

“There is a real need for a clinically efficacious, safe and cost-effective way to form bone,” said Wellington Hsu, a spine surgeon. “The success of this nanomaterial makes me excited that every spine surgeon may one day subscribe to this method for bone graft. Right now, if you poll an audience of spine surgeons, you will get 15 to 20 different answers on what they use for bone graft. We need to standardize choice and improve patient outcomes.”

In the in vivo portion of the study, the nanomaterial was delivered to the spine using a collagen sponge. This is the way surgeons currently deliver BMP-2 clinically to promote bone growth.

The Northwestern research team plans to seek approval from the Food and Drug Administration to launch a clinical trial studying the nanomaterial for bone regeneration in humans.

“We surgeons are looking for optimal carriers for growth factors and cells,” Wellington Hsu said. “With its numerous binding sites, the long filaments of this new nanomaterial is more successful than existing carriers in releasing the growth factor when the body is ready. Timing is critical for success in bone regeneration.”

In the new nanomaterial, the sugars are displayed in a scaffold built from self-assembling molecules known as peptide amphiphiles, first developed by Stupp 15 years ago. These synthetic molecules have been essential in his work on regenerative medicine.

“We focused on bone regeneration to demonstrate the power of the sugar nanostructure to provide a big signaling boost,” Stupp said. “With small design changes, the method could be used with other growth factors for the regeneration of all kinds of tissues. One day we may be able to fully do away with the use of growth factors made by recombinant biotechnology and instead empower the natural ones in our bodies.”

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

Sulfated glycopeptide nanostructures for multipotent protein activation by Sungsoo S. Lee, Timmy Fyrner, Feng Chen, Zaida Álvarez, Eduard Sleep, Danielle S. Chun, Joseph A. Weiner, Ralph W. Cook, Ryan D. Freshman, Michael S. Schallmo, Karina M. Katchko, Andrew D. Schneider, Justin T. Smith, Chawon Yun, Gurmit Singh, Sohaib Z. Hashmi, Mark T. McClendon, Zhilin Yu, Stuart R. Stock, Wellington K. Hsu, Erin L. Hsu, & Samuel I. Stupp. Nature Nanotechnology 12, 821–829 (2017) doi:10.1038/nnano.2017.109 Published online 19 June 2017

This paper is behind a paywall.

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.

NANoReg invites you to April 11, 2014 workshop in Athens, Greece

For anyone interested in nanomaterials and/or attending an EHS-themed (environment, health, and safety) event in Athens, Greece, NANoREG is holding an April 2014 workshop at the Industrial Technologies 2014 conference (April 9 – 11, 2014). From a March 14, 2014 news item on Nanowerk (Some links have been removed),

NANoREG will identify EHS [environment, health, and safety] aspects that are most relevant from a regulatory point of view. It will provide tools for testing the EHS aspects and the assessment and management of the risks to the regulators and other stakeholders.

To assure that the final results of the project can be implemented in an efficient and effective way, Industry and Regulators are strongly involved in the project.
We kindly invite you to attend the NANoREG workshop and to give your opinion on the regulatory testing of nanomaterials, as a valuable contribution to future economic success of nanotechnology!

The workshop will take place on Friday, April 11, 2014 from 11:15 a.m. to 1:30 p.m. in Athens, Greece, as part of the Industrial Technologies 2014 event. For registration please use the offi cial registration portal: www.naturalway.gr/industrial_technologies

Here’s more about the workshop from the NANoREG workshop page on the Industrial Technologies 2014 website,

1. The NANoREG approach: Answers from Science to the questions/needs of Industry and the Regulation Authorities.
2. First entrypoints, the regulatory questions and needs, an overview, matching of needs
3. NANoREG results: Materials, SOPs and the advancement of Regulatory Risk Assessment and Testing.
4.Overview of the NANoREG projects.
5. Whe window for industry participation, keeping pace with innovation.
6. Modes of collaboartion [sic] for industry.
7. Outlook

A joint workshops of EU FP7 Projects SANOWORK, nanoMICEX and Scaffold funded under the topic NMP.2011.1.3-2 “Worker Protection and exposure risk management strategies for nanomaterials production, use and disposal”, will focus on the main achievements of the three Projects in the related area. All three projects are committed to support the needs of companies and aim to provide a practical overview of the results of current research in the field of management of exposure to nanomaterials.

Here are links to the other three projects collaborating on the NANoREG workshop  SANOWORKnanoMICEX, and Scaffold.