A therapy for traumatic brain injury?

To counter the damaging secondary effects of traumatic brain injury, researchers in Vivek Kumar’s Biomaterial Drug Development, Discovery and Delivery Laboratory are developing a hydrogel therapy to protect neurons and promote their regeneration.

A blow to the head or powerful shock wave on the battlefield can cause immediate, significant damage to a person’s skull and the tissue beneath it. But the trauma does not stop there. The impact sets off a chemical reaction in the brain that ravages neurons and the networks that supply them with nutrients and oxygen.

It is the secondary effects of traumatic brain injury (TBI), which can lead to long-term cognitive, psychological and motor system damage, that piqued the interest of a team of NJIT biomedical engineers. To counter them, they are developing a therapy, to be injected at the site of the injury, which shows early indications it can protect neurons and stimulate the regrowth of blood vessels in the damaged tissue.

The challenge, researchers say, is that brain cells don’t regenerate as well as other tissues, such as bone, which may be an evolutionary strategy for preserving the synaptic connections that retain memories. To date, there is no effective treatment for restoring damaged neurons. The body’s protective mechanisms also make it difficult to penetrate the blood-brain barrier, which hampers the delivery of medications.

“Nerve cells respond to trauma by producing excessive amounts of glutamate, a neurotransmitter that under normal conditions facilitates learning and memory, but at toxic levels overexcites cells, causing them to break down. Traumatic brain injury can also result in the activation and recruitment of immune cells, which cause inflammation that can lead to short- and long-term neural deficits by damaging the structure around cells and creating a chronic inflammatory environment,” says Biplab Sarkar, a post-doctoral fellow in biomedical engineering and member of the team that presented this work at a recent American Chemical Society conference.

The team’s treatment consists of a lab-created mimic of ependymin, a protein shown to protect neurons after injury, attached to a delivery platform – a strand of short proteins called peptides, contained in a hydrogel – that was developed by Vivek Kumar, director of NJIT’s Biomaterial Drug Development, Discovery and Delivery Laboratory. After injection, the peptides in the hydrogel reassemble at the localized injury site into a nanofibrous scaffold that mimics extracellular matrix, the supporting structure for cells. These soft materials possess mechanical properties similar to brain tissue, which improves their biocompatibility. They promote rapid infiltration by a variety of stem cells which act as precursors for regeneration and may also provide a biomimetic niche to protect them.

Now in preclinical animal trials, rats injected with the hydrogel retained twice as many functioning neurons at the injury site as compared to the control group. They also formed new blood cells in the region.

“The idea is to intervene at the right time and place to minimize or reverse damage. We do this by generating new blood vessels in the area to restore oxygen exchange, which is reduced in patients with a TBI, and by creating an environment in which neurons that have been damaged in the injury are supported and can thrive,” Kumar says. “While the exact mechanism of action for these materials is currently under study, their efficacy is becoming apparent. Our results need to be expanded, however, into a better understanding of these mechanisms at the cellular level, as well as their long-term efficacy and the resulting behavioral improvements.”

Collaborators James Haorah, an associate professor of biomedical engineering, and his graduate student Xiaotang Ma at NJIT’s Center for Injury Biomechanics, Materials and Medicine have shown how a number of TBI-related chemical effects can disrupt and destroy integral brain vasculature in the blood-brain barrier, the brain’s protective border, promoting chronic inflammation that can lead to symptoms such as post-traumatic stress disorder and anxiety, among others. Their current work provides insights into the potential neuroprotective and regenerative response guided by the Kumar lab’s materials, while future studies will attempt to analyze other mediators of inflammation and blood flow in the brain.

Kumar’s delivery mechanism is a customizable, Lego-like strand made of short proteins called peptides, which are composed of amino acids, with a biological agent attached at one end that can survive in the body for weeks and even months, where other biomaterials degrade quickly. Its self-assembling bonds are designed to be stronger than the body’s dispersive forces; it forms stable fibers, with no signs of inducing inflammation, that rapidly incorporate into specific tissues and collagen, recruiting native cells to infiltrate. The hydrogel, which is also composed of amino acids, is engineered to trigger different biological responses depending on the payload attached. These platforms can deliver drugs and other small cargo over day-, week- or month-long periods. Kumar’s lab has recently published research on applications ranging from therapies to prompt or prevent the creation of new blood vessel networks, to reduce inflammation and to combat microbes.

“The ultimate hope is that that localized delivery of regenerative materials may provide significant benefits for a number of pathologies,” he notes.

For example, the team recently developed a class of materials that may be useful against infection. These novel anti-microbial peptides are capable of disrupting dense bacterial colonies and have shown promise against a number of yeasts. Additionally, they promote human cell proliferation and are currently being studied for wound healing. That work was published in August in the journal ACS Biomaterials Science and Engineering.

Kumar and his lab have created another hydrogel designed to recruit autologous (a person’s own) dental pulp stem cells directly to the disinfected cavity after root canal therapy. The tooth would be regenerated in part by prompting growth of the necessary blood vessels to support the new tissue. Yet another peptide-based therapy, armed with antiangiogenic capabilities, targets diabetic retinopathy, an ocular disease affecting more than 90 million people worldwide. People with the disease form immature blood vessels in the retina, obstructing their vision. The hydrogel can be injected directly into the vitreous gel of the eye, where the peptide interacts with the endothelial cells in the aberrant blood vessels, causing them to die.

“Conventional biomaterials used in tissue regeneration suffer from a variety of problems with delivery, retention and biocompatibility, which can lead to rejection by the host,” Kumar says. “We’re trying to address these issues with a technology designed to be universal in its application, delivering materials that persist in the tissue and promote their biologic effects for long periods of time.”

Learn more: Dealing a Therapeutic Counterblow to Traumatic Brain Injury

 

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A nanotechnology-enhanced biochip could detect cancers, malaria and viral diseases in their progression with a pin prick blood test

via Oncology News Australia

The difficulty in spotting minute amounts of disease circulating in the bloodstream has proven a stumbling block in the detection and treatment of cancers that advance stealthily with few symptoms. With a novel electrochemical biosensing device that identifies the tiniest signals these biomarkers emit, a pair of NJIT inventors are hoping to bridge this gap.

Their work in disease detection is an illustration of the power of electrical sensing – and the growing role of engineers – in medical research.

“Ideally, there would be a simple, inexpensive test – performed at a regular patient visit in the absence of specific symptoms – to screen for some of the more silent, deadly cancers,” says Bharath Babu Nunna, a recent Ph.D. graduate who worked with Eon Soo Lee, an assistant professor of mechanical engineering, to develop a nanotechnology-enhanced biochip to detect cancers, malaria and viral diseases such as pneumonia early in their progression with a pin prick blood test.

Their device includes a microfluidic channel through which a tiny amount of drawn blood flows past a sensing platform coated with biological agents that bind with targeted biomarkers of disease in body fluids such as blood, tears and urine – thereby triggering an electrical nanocircuit that signals their presence.

One of the device’s core innovations is the ability to separate blood plasma from whole blood in its microfluidic channels. Blood plasma carries the disease biomarkers and it is therefore necessary to separate it to enhance the “signal to noise ratio” in order to achieve a highly accurate test. The standalone device analyzes a blood sample within two minutes with no need for external equipment.

“Our approach detects targeted disease biomolecules at the femto scale concentration, which is smaller than nano and even pico scale, and is akin to searching for a planet in a galaxy cluster. Current sensing technology is limited to concentrations a thousand times larger. Using a nanoscale platform allows us to identify these lower levels of disease,” Nunna says, adding, “And by separating the plasma from the blood, we are able to concentrate the disease biomarkers.”

Nunna is now a postdoctoral research fellow at Harvard Medical School, where he is expanding his expertise in microfluidic platforms, using them in organ-on-the-chip research conducted with Su Ryon Shin, a principal investigator and instructor in the medical school’s Department of Medicine who develops 3D-bioprinted organoids – artificial organs composed of cultured cells within structured hydrogels – for medical experimentation.

“I’m primarily responsible for developing the microfluidic devices that will automate the process of bioprinting 3D organs that will be incorporated on a chip for a number of purposes. I’m tasked, for example, with developing an automated platform for long-term drug efficacy and toxicity analysis to track liver cancer and cardiac biomarkers. I’ll be integrating the microfluidic biosensor with the liver cancer- and heart-on-a-chip model for continuous monitoring,” he says.

By measuring the biomarker concentrations secreted from drug-injected 3D-bioprinted organs, we can study drug effects on several organs without harming a live patient. Creating artificial organs allows us to experiment freely.”

Down the road, he adds, the work at Harvard could potentially be applied in regenerative medicine. “The goal is to develop fully functional 3D-bioprinted organoids and clinically relevant 3D tissues to address the issue of donor shortages in transplantation.”

Nunna says his research at Harvard Medical School will expand his knowledge of programmable microfluidics and precise electrochemical sensing techniques, which will in turn help him advance his biochip technology. The goal is a simple, standard assay for cancer diagnosis that avoids conventional, complex diagnostic steps.

Lee and Nunna have been working with oncologists at Weill Cornell Medicine and Hackensack Medical Center to identify clinical applications. As currently designed, the device would provide both qualitative and quantitative results of cancer antigens in blood samples, providing information on the presence and the severity of the cancer. Their next step, he says, will be to expand the platform to detect multiple diseases using a single blood sample obtained with a pin prick.

“Although healthcare technology is considered to be a fast-evolving technology, there are still many unmet needs that need to be addressed. Diagnosing potentially deadly diseases at the early stages is the key to saving lives and improving patient treatment outcomes,” he says, adding, “There is a huge need for healthcare technology, including a universal diagnostic platform that can provide instant results at the physician’s office and other point-of-care settings.”

Nunna is the co-founder and chief research scientist for Abonics, Inc., a startup formed by Lee to commercialize their device. He is named as a co-inventor with Lee on three published biochip patents and six additional patents that are now under review by the U.S. Patent and Trademark Office. Their technology has won financial backing from the National Science Foundation I-Corps program and the New Jersey Health Foundation (NJHF), a not-for-profit corporation that supports top biomedical research and health-related education programs in New Jersey.

“As we know, early detection can improve treatment outcomes for patients significantly,” explained George F. Heinrich, M.D., vice chair and CEO of NJHF, in announcing the award. “Currently, doctors rely on diagnostic devices requiring a minimum of four hours of sample preparation through centralized diagnostic centers rather than their local offices.”

In 2017, Nunna received the “Best Design in Healthcare Innovations and Point-of-Care Innovations Award” at the Healthcare Innovation and Point-of-Care Technologies conference from the Engineering in Medicine and Biology Society, held at the National Institute of Health headquarters in Bethesda, MD.  That same year, the technology received the national innovation award at the TechConnect World Innovation Conference and Expo, an annual gathering of technology transfer offices, companies, and investment firms who meet to identify promising technologies from across the globe.

“I come from an engineering background with experience in developing large machinery for the company, Caterpillar. The connection to my present work is particle transportation in fluid dynamics – identifying the unique sensing signals that particular particles generate in a dynamic fluid environment,” he notes. “It has been very exciting to work with Eon Soo Lee, who is one of the leaders in the field of microfluidic biosensing. He introduced me to a fascinating new career that took me from the production plant to the cleanroom environment at Brookhaven National Laboratory. Importantly, he gave me the freedom to test out novel ideas.”

Learn more: Minute levels of disease detected with nanotechnology-enhanced biochip

 

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A 114% quantum step towards the production of hydrogen fuel

via New Jersey Institute of Technology

Efforts to reduce our dependence on fossil fuels are advancing on various significant fronts. Such initiatives include research focused on more efficient production of gaseous hydrogen fuel by using solar energy to break water down into its components of hydrogen and oxygen.

Recently, in an article published in the journal Nature Energy, lead author Yong Yan, an assistant professor in the Department of Chemistry and Environmental Science, reported a key breakthrough in the basic science essential for progress toward this goal.

The article, “Multiple exciton generation for photoelectrochemical hydrogen evolution reactions with quantum yields exceeding 100%,” reports on the investigative work that Yan carried out along with colleagues affiliated with the National Renewable Energy Laboratory, the Colorado School of Mines and San Diego State University. Essentially, they created what is known as a quantum dot photoelectrochemical cell that catalytically achieved quantum efficiency for hydrogen gas production exceeding 100% — in the case of their experiments an efficiency approaching 114%.

Quantum dots are extremely small semiconductor particles only a few nanometers in size. (A nanometer is one-billionth of a meter.) In their device, lead sulfide quantum dots replace semiconductor materials such as silicon and copper indium gallium arsenide. The advantage is that such a photoelectrochemical device can, potentially, convert a greater portion of the solar spectrum into useful energy.

The device described is able to absorb one visible solar photon and produce two, or even more, electrons through a process known as multiple exciton generation, or MEG, which are further utilized to reduce water to generate hydrogen gas. Although many scientists worldwide are engaged in efforts to achieve quantum efficiency as close as possible to 100% for solar hydrogen production, Yan’s achievement in directly exceeding this threshold is a significant fundamental breakthrough. It clearly proves that the photoelectrochemical cell design he describes is much more efficient than a quantum dot solar cell with respect to quantum yield.

Yan, who joined the NJIT faculty in 2016, emphasizes that this advance is at the level of basic solar science, and that the breakthrough with respect to quantum yield does not equate to a substantial increase in the ultimate solar-to-hydrogen conversion efficiency. Nonetheless, this dramatic increase in quantum yield realized with a uniquely innovative lead sulfide quantum dot photoelectrochemical device is an important development in several ways, and as such is a product of Yan’s long-standing interest in renewable sources of energy, especially in novel applications of solar energy.

For Yan, the research reported in Nature Energy culminated at NJIT after his previous work as a postdoc at Princeton University and at the U.S. Department of Energy’s National Renewable Energy Laboratory in Colorado. The success of this leading-edge effort was made possible with funding provided, in part, by NJIT and the Department of Energy.

Yan says, “These results do present the possibility of generating more energy more efficiently with such a solar-capture device in the future. This could also lead to a fundamental change in the entire process of producing hydrogen fuel. We can now obtain hydrogen fuel from water by using electricity supplied by conventional power plants that consume fossil fuels. But by building on the basic step of achieving such high quantum efficiency for solar hydrogen generation, we could make the process of producing a ‘green’ fuel much greener as well.”

Learn More: A More Than 100% Quantum Step Toward Producing Hydrogen Fuel

 

 

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NJIT Professor Invents a Flexible Battery

flexible-battery

NJIT Professor Som Mitra (left) invented a flexible battery with assistance from Zhiqian Wang, a doctoral student in chemistry.

Researchers at NJIT have developed a flexible battery made with carbon nanotubes that could potentially power electronic devices with flexible displays.

Electronic manufacturers are now making flexible organic light-emitting diode (OLED) displays, a pioneering technology that allow devices such as cell phones, tablet computers and TVs to literally fold up.

And this new battery, given its flexibility and components, can be used to power this new generation of bendable electronics. The battery is made from carbon nanotubes and micro-particles that serve as active components — similar to those found in conventional batteries. It is designed, though, to contain the electro-active ingredients while remaining flexible.

“This battery can be made as small as a pinhead or as large as a carpet in your living room,” says Somenath Mitra, a professor of chemistry and environmental science whose research group invented the battery. “So its applications are endless. You can place a rolled-up battery in the trunk of your electric car and have it power the vehicle.”

A patent application on the battery has been filed, and the battery will be featured in an upcoming issue of “Advanced Materials.”  Mitra developed the new technology at NJIT with assistance from Zhiqian Wang, a doctoral student in chemistry.

The battery has another revolutionary potential, in that it could be fabricated at home by consumers.  All one would need to make the battery is a kit comprised of electrode paste and a laminating machine. One would coat two plastic sheets with the electrode paste, place a plastic separator between the sheets and then laminate the assembly. The battery assembly would function in the same way as a double-A or a triple-A battery.

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Robotic Ants Successfully Mimic Real Colony Behavior

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Scientists have successfully replicated the behaviour of a colony of ants on the move with the use of miniature robots, as reported in the journal PLOS Computational Biology.

The researchers, based at the New Jersey Institute of Technology (Newark, USA) and at the Research Centre on Animal Cognition (Toulouse, France), aimed to discover how individual ants, when part of a moving colony, orient themselves in the labyrinthine pathways that stretch from their nest to various food sources.

The study focused mainly on how Argentine ants behave and coordinate themselves in both symmetrical and asymmetrical pathways. In nature, ants do this by leaving chemical pheromone trails. This was reproduced by a swarm of sugar cube size robots, called “Alices,” leaving light trails that they can detect with two light sensors mimicking the role of the ants’ antennae.

In the beginning of the experiment, where branches of the maze had no light trail, the robots adopted an “exploratory behaviour” modelled on the regular insect movement pattern of moving randomly but in the same general direction. This led the robots to choose the path that deviated least from their trajectory at each bifurcation of the network. If the robots detected a light trail, they would turn to follow that path.

One outcome of the robotic model was the discovery that the robots did not need to be programmed to identify and compute the geometry of the network bifurcations. They managed to navigate the maze using only the pheromone light trail and the programmed directional random walk, which directed them to the more direct route between their starting area and a target area on the periphery of the maze. Individual Argentine ants have poor eyesight and move too quickly to make a calculated decision about their direction. Therefore the fact that the robots managed to orient themselves in the maze in a similar fashion than the one observed in real ants suggests that a complex cognitive process is not necessary for colonies of ants to navigate efficiently in their complex network of foraging trails.

Read more . . .

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