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Foundation Supports ALS Inflammation Treatments

Brain activity graphic

(Gordon Johnson, Pixabay)

17 Feb. 2020. A foundation is funding a biotechnology company’s research on therapies to block proteins encouraging neuron inflammation in people with amyotrophic lateral sclerosis, or ALS. The ALS Association in Arlington, Virginia is providing a $500,000 grant to support the work of Neuropore Therapies Inc. in San Diego.

ALS, also known as Lou Gehrig’s disease, is a progressive neurodegenerative disorder where neurons or nerve cells controlling muscles in the body begin to waste away, and can no longer send or receive signals from the brain or spinal cord. As the nerve cells stop functioning, muscles in the limbs, and later speech and breathing muscles, begin weakening and eventually stop functioning. Most people with the disease die of respiratory failure.

Neuropore Therapies discovers and develops treatments for neurodegenerative disorders. The company focuses particularly on diseases from accumulations of toxic misfolded proteins in neurons in the brain, and the chronic and damaging inflammation of neurons that instigates or drives progressive neurodegeneration. Neuropore’s pipeline includes therapies in clinical trials and preclinical development for Parkinson’s disease and ALS.

One of Neuropore’s targets is a set of proteins called toll-like receptors that detect foreign microbes in the body. Toll-like receptors stimulate innate, or general, defense mechanisms in the immune system, as well as responses to specific pathogens. In the brain, however, toll-like receptors can drive chronic inflammation that damages neurons in people with ALS and Parkinson’s disease.

Neuropore developed a treatment code-named NPT1220-312 that blocks a subset of toll-like receptors in the brain, known as toll-like receptor 2 or TLR2 proteins associated with ALS and Parkinson’s disease inflammation. “Targeting TLR2 is an exciting new approach to the treatment of ALS,” says Doug Bonhaus, Neuropore’s CEO and chief scientist in a company statement released through BusinessWire. “NPT1220-312 is a potent, selective, orally-bioavailable TLR2 antagonist. It has shown robust beneficial actions in cell-based assays and in an animal models of ALS.”

ALS Association is an advocacy and research funding organization seeking to find effective treatments for ALS, and provide support for patients with ALS and their families. The group is funding the Neuropore work from its drug development program that supports preclinical studies and clinical trials by academic labs and industry teams.

Bonhaus adds, “Pending positive outcomes in ongoing studies, our goal is to submit an IND application for NPT1220-312 to FDA by first half of 2021.” IND is short for investigational new drug application, in effect clearance from FDA to begin clinical trials of an experimental drug or biologic therapy.

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Waste Plastic-to-Energy System Unveiled

Waste plastic cups

(meineresterampe, Pixabay)

17 Feb. 2020. A company developing waste-to-energy conversion systems revealed a version of its product that converts waste plastic to heat and electric power. Enexor BioEnergy in Franklin, Tennessee unveiled yesterday its PTE-200 system that combines chemical processing with high pressure and temperatures in a self-contained unit resembling a shipping container.

Enexor BioEnergy says its PTE-200 system diverts non-recyclable plastic waste from landfills and microplastics into usable energy. According to the U.N. Environmental Program, humans produce about 300 million metric tons of plastic waste each year, nearly as much as the weight of the entire human population on earth. Since he 1950s, says the U.N. agency, the world produced some 8.3 billion metric tons of plastic, about 60 percent of which ended up in landfills, and nearly all of which  is derived form fossil fuels. And as reported by Science & Enterprise in June 2018, China plans by 2030 to stop importing waste plastic, accounting for more than 72 percent of the world’s trade in this material.

The company says its technology, called Bio-CHP, can process many kinds of organic bio-waste — wood chips, saw dust, agricultural residues, food waste, animal waste, disposed cardboard and paper — as well as plastics. The raw waste is oxidized under high heat and pressure that break down the organic materials. At the same time, the process filters out and stores non-organic particulates for later disposal. Enexor does not indicate the volume of inorganic materials produced by its process.

The hot pressurized gas produced by the process heats ambient air sent through a self-contained turbine that produces electrical power. In addition, this exhaust gas can be sent through a heat exchanger to generate hot water or steam.

The company says its units generate 75 kilowatts of electrical power and the equivalent of 125 kilowatts of thermal energy, sufficient to power more than 100 standard homes. The units can also be sited at hospitals, telecommunications towers, water pumping systems, or shopping centers, and integrated into local microgrids to supplement renewable energy sources. Enexor offers operating plans for customers to avoid high upfront costs, where the company manages the systems remotely and charges only for energy produced by its units.

The PTE-200 system for converting plastics is a variation of Enexor’s multiple-feedstock Bio-200 system announced earlier this month. The company plans to market the PTE-200 low-resource regions for communities with both mounting waste plastic stockpiles and a lack of reliable energy sources, starting in Latin America and Asia.

“The majority of the world’s plastic pollution is located where the most disadvantaged people in the world live,” says Lee Jestings, Exenor’s founder and CEO in a company statement. “These areas are also the most energy-deprived. Our PTE-200 systems can be installed where they are needed the most, at the convergence of plastic waste and energy impoverished communities.”

Exenor BioEnergy is a five year-old company that, according to Crunchbase, raised $5 million in seed-round funding in July 2019.

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Infographic – U.S. Having Bad Flu Season

Chart: US flu season

(Statista)

15 Feb. 2020. While much of the world’s attention is focused on the novel coronavirus, now code-named COVID-19, the flu season in the U.S. is no day at the beach either. According to data from the Centers for Disease Control and Prevention, the infection rate for this year’s seasonal influenza is among the highest in the past five years.

The business research company Statista charted the CDC’s data, displayed in our weekend infographic. Not only did the rate of positive lab test specimens in late January reach nearly 28 percent, that rate began dropping during the first part of January, only to rebound toward the end of the month. And not shown on the chart is the latest report from CDC showing the positive test rate rising last week to nearly 31 percent.

The best protection against the flu, of course, is the annual flu vaccine, particularly for people at higher risk of infection: those age 65 and older, pregnant women, young children, and people with chronic diseases. And don’t put it off. CDC estimates that so far this season, the flu caused at least 12 million medical visits, 250,000 hospitalizations, and 14,000 deaths in the U.S.

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Infant Jumpsuit Captures Objective Movement Data

Smart jumpsuit

Child in smart jumpsuit (Sampsa Vanhatalo, University of Helsinki)

14 Feb. 2020. A one-piece garment fitted with sensors is shown to capture data about an infant’s movements for analysis by algorithms to reveal possible developmental problems. A description of the baby’s high-tech play wear and the algorithms for analysis appear last month in the journal Scientific Reports.

Researchers from University of Helsinki and Aalto University in Espoo, Finland are seeking more objective methods for assessing a child’s early neurological development, often revealed by atypical movements of the limbs and torso. While developmental conditions such as cerebral palsy and autism spectrum disorders can be detected early on by observing infants at play, these observations can be subjective and are not easily quantified. In addition, children may not spontaneously play in an unfamiliar setting, like a doctor’s office, thus capturing a child’s movements unobtrusively while at home would likely provide more accurate data.

A team led by University of Helsinki neuroscientist Sampsa Vanhatalo developed a one-piece garment resembling a jumpsuit for infants as young as five months to wear while they play at home. Sewn into the soft fabric are accelerometer and gyroscope sensors devised by Movesense, an open-source wearable project, with the devices positioned in the upper arms and legs. Data captured by the sensors are sent via Bluetooth to a nearby receiver. There, the data are processed and displayed with software by the German company Kaasa, a participant in the Movesense project.

Vanhatalo and colleagues asked parents of 22 typically-developed infants about seven months old, to have their children wear the jumpsuits at home. While the infants played in the jumpsuits, the devices captured data sent to the receiving systems, and were also video-recorded. Child development experts then observed the videos of infants at play and annotated the clips with a characterization scheme for posture and movement patterns of children that age.

With that movement characterization scheme, the researchers developed algorithms for analyzing movement data collected by sensors in infants’ jumpsuits. The algorithms use a convolutional neural network, a type of artificial intelligence that combines image analysis and deep machine learning to dissect an image by layers for understanding features in the image. Different aspects of each layer discovered and analyzed by the system are translated into data that the algorithm then uses to train its understanding of the problem being solved, with that understanding enhanced and refined as more images and data are encountered.

The team carried out a series of experiments comparing expert observations of the children’s motility or independent movements to results produced by algorithms from the sensor data. One proof-of-concept test evaluated results of experts’ ratings of five children with higher motor performance and five lower-performing infants. Separate assessments using data from the jumpsuit sensors and analyzed by the algorithm returned similar results.

“The smart jumpsuit provides us with the first opportunity to quantify infants’ spontaneous and voluntary movements outside the laboratory,” says Vanhatalo in a Helsinki University statement. He adds, “The measurements provide a tool to detect the precise variation in motility from the age of five months, something which medical smart clothes have not been able to do until now.”

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Wireless Smart Bandage Designed for Chronic Wounds

Hand bandage

(Rawpixel, Pexels.com)

14 Feb. 2020. A university lab developed a wirelessly-controlled programmable bandage that in tests with lab mice results in more diabetic wound closure than topical medicines. Researchers from University of Connecticut in Farmington and University of Nebraska in Lincoln describe the device in yesterday’s issue of the journal Advanced Functional Materials (paid subscription required).

A team led by biomedical engineer Ali Tamayol, on the faculty at Connecticut and Nebraska, is seeking more effective treatments for chronic diabetic skin ulcers. Many people with diabetes develop slow-healing skin ulcers on their feet, a common complication of the disease. In people with diabetes, blood flow is reduced to the legs and feet, leading to nerve damage and reduced feeling in those regions, as well as slower healing of wounds. Centers for Disease Control and Prevention says in 2014, some 108,000 Americans required amputation of a leg or foot because of complications from diabetes.

The authors note that despite advances in finding medications to treat chronic diabetic skin ulcers, patients often need different medications as healing progresses on the wound, which makes treating the wounds more complex. As a result, the researchers designed a bandage able to dispense different medications as needed to promote healing of the wound, yet could also be programmed or controlled by the wearer.

The bandage device created by the UConn-Nebraska team uses 3-D printed miniature needles that penetrate the outer layers of the patient’s wound. The needles are hollowed out and attached to a reservoir for medications made from polydimethylsiloxane, or PDMS, a soft, flexible biocompatible polymer used in many biomedical applications. The bandage’s needles are minimally invasive, causing little apparent pain or inflammation.

Different medications can be stored in the reservoir, with their application through the needles controlled by wireless commands from a nearby controller, with software that can be hosted by a smartphone. “This is an important step in engineering advanced bandages that can facilitate the healing of hard to treat wounds,” says Tamayol in a UConn statement. “The bandage does not need to be changed continuously.”

To prove the concept, the researchers tested their bandage device in lab mice induced with diabetic skin ulcers penetrating the entire skin thickness. For the study, the device dispensed vascular endothelial growth factors, or VEGFs, proteins that encourage regeneration of blood vessels, but also other types of tissue. The results show wounds on mice with the smart bandage healed to a greater extent, including more blood vessels and hair growth, than mice with comparable wounds treated with VEGF as a topical medication.

The authors say the findings indicate their programmable bandage device can reduce the burden of chronic diabetic skin wounds on individuals and health care systems. UConn adds that Tamayol applied for a patent on the technology.

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Controlling Your Business’s Narrative

– Contributed content –

Business newspaper

(Rawpixel, Unsplash)

14 Feb. 2020. The most successful businesses in the world all have their own stories, from the esoteric (do you know how Coca-Cola first came into the public realm?) to the standard. What they all have in common, though, is that these stories are by now a matter of public record, for better or worse. When you are starting your business, you may not be thinking about much more than whether you can avoid being one of those companies that fails in its first year – don’t worry, the stat of 50% has been conclusively debunked – but you’re writing your story whether or not you realize it.

A story can be a powerful thing to have as a business, especially as numbers suggest that consumers are now more likely than ever to gravitate to businesses with a positive ethos. And while you are likely to spend the early days just trying to get your business off the ground, it’s important that you think about how you write that story. You want to control your narrative, because when people hear your story, you want them to take a positive message from it.

What difference does a positive story make?

In the present generation, an increasing number of consumers have strong ideas about which kind of business they want to give their custom to. This tends to be exemplified by being prepared to pay extra for sustainably-sourced products, or businesses that pay a living wage. If you can point to a back story of being an ethical business – showing “receipts” both metaphorically and in some cases literally – then you can appeal to a growing audience.

How do you make your story positive?

Your story isn’t just about your company’s origins and the people who work for it. It also has to do with how you conduct yourself as a business, and how you interact with clients. If you do business with resellers, then protecting the honest ones from being undercut by unfair competition is part of how you control your narrative. In this way, MAP compliance software is as powerful a tool as any content you may put on your website. Your loyal clients will be a testament to your fairness.

How do you tell a story?

Increasingly, social media is becoming an effective way for businesses to get their stories out there. Sometimes, you might hand the company Twitter account over to different members of staff, or even give a camera to a new employee who can vlog about a typical day on the job for them. The authenticity of this approach doesn’t just offer a fun selling point in the now – it also can build into a handy “back story” that will document the development of your company from the acorn of an idea to the great oak it will one day become.

Customers will always be happier to give their loyalty to a company that takes a positive approach, and you can attract that customer base by being open and telling your story as a company. Among other benefits, this allows you to protect your legacy by being the person who tells the real story.

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Enrollment Completed in Aging Frailty Stem Cell Trial

Hands of older person

(Steve Buissinne, Pixabay)

13 Feb. 2020. A company developing stem cell treatments to counter frailty in older people finished enlisting participants in a clinical trial testing its therapies. Longeveron LLC in Miami is conducting the mid-stage trial with 150 individuals at seven test sites in Florida.

Longeveron develops therapies for age-related diseases from human mesenchymal stem cells. Mesenchymal stem cells are so-called adult stem cells, derived from existing cells or tissue, in this case, bone marrow, rather than human embryos. Longeveron acquires donated bone marrow from young, healthy volunteers, then processes the donations in the company’s lab to extract stem cells for allogenic, or off-the-shelf infusions in patients. The company is creating treatments from these stem cells for frailty, metabolic disorder, and Alzheimer’s disease in older individuals, as well as congenital heart defects in children.

Frailty in older adults, usually people older than 65, is recognized as a geriatric syndrome indicated by weakness, low activity, and weight loss. The condition helps make older individuals vulnerable to other diseases, by lowering their ability to counter internal stresses. “The biology of frailty is complex,” says Anthony Oliva, senior scientist at Longeveron in a company statement released through PRNewswire, “and includes diminished stem cell activity, reduced ability to repair and regenerate tissue, and chronic systemic inflammation.”

Longeveron says its stem cell infusions restore stem cell levels to help reduce inflammation, promote internal tissue repair, and improve immune system performance. As a result, the company believes its treatments can help people in frail condition, estimated at 7 to 12 percent of people age 65 and older, increase their strength, stamina, and mobility. Longeveron says earlier clinical trials established the safety of its stem cell treatments.

The new clinical trial is testing Longeveron’s stem cell treatments among 150 older individuals, age 70 to 85, and scored mildly or moderately frail on a standard rating scale. Participants are randomly assigned to receive one of four doses — 25, 50, 100, or 200 million –stem cells, or a placebo, in a single infusion. The study team is looking primarily at the distance participants can walk for six minutes before stem cell or placebo infusions, and 180 days later. Participants are also rated on changes in overall physical functioning, as well as levels of an inflammatory cytokine called tumor necrosis factor alpha, or TNF alpha.

“This study,” says Longeveron’s president Geoff Green, “is designed to determine whether the transplant of healthy donor-derived mesenchymal stem cells can restore mild to moderately frail patients to a state of more healthful aging, thereby improving functionality and lowering their risk of disability, and dependence on others for care.”

The clinical trial is funded by a Small Business Innovation Research, or SBIR, grant from National Institute on Aging, part of National Institutes of Health. Funding from the grant, awarded in October 2018, is set to end on 29 February 2020.

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Time Saving Techniques for Your Business

– Contributed content –

Apple smartwatch

(Fancycrave1, Pixabay)

13 Feb. 2020. As a business owner, you know that time is much more precious than money at the moment. If you had more hours in the day you could carry out more needle moving tasks to get your business to the next level. A lot of entrepreneurs struggle with time management, so there are a few solutions that might help you. You might be struggling to hire due to lack of time and resources; maybe you don’t have time to run your social media accounts. There are a number of reasons why you’re low on hours in the day, so here’s how you can rectify that.

Virtual interviews

When you are desperate for new members of staff but you don’t have the time to onboard, the pressure can start to mount. This is a catch 22 situation as you need the additional help, but you don’t have the resources to conduct in depth interviews. This is where a digital interview could come in useful. With this modern day technology you have everything you need to interview and hire any candidate for a job. This is one quick and convenient way to save time within your business.

As a business owner, you know how important it is to stay consistent on social media. If your brand isn’t in front of your audience every single day they can quickly lose interest and move onto the next big thing. This is where social media scheduling tools come in very handy. You can essentially map out an entire month’s worth of content and have apps such as Buffer and Planoly publish your posts whilst you work. Although you will need to engage on social media in order for the algorithms to favor you, this is a sure fire time saver for every business owner.

Guest bloggers

Keeping up with blogging is so time consuming; it’s not something you are passionate about and you struggle to create innovative content. This is where guest bloggers come in very useful. They can write about topics that are interesting to your target audience and keep your blog content topped up. Blogging is well worth it as popular search engines will push you up the rankings as you include more and more relevant keywords.

Quarterly goal setting

Instead of setting monthly or yearly goals, many business owners are opting for quarterly goals. This method will give you a bird’s eye view of how your business is going to operate every three months. Setting a goal for each quarter is much more manageable and digestible than trying to accomplish it all in a year. When you set your goals in this way it will save your a lot of time and energy as you are actually being realistic with your time periods.

Hopefully some of these techniques will prove to be extremely useful to you whilst you take your business to the next level. You don’t necessarily have to be running a big corporate business to make use of these tools. You simply need to assess what is going to give you back some much needed hours during the day.

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Engineered Bacteria Deliver Cancer Immunotherapy

E. coli

Escherichia coli, or E. coli, bacteria (National Institute of Allergy and Infectious Diseases)

13 Feb. 2020. A biomedical engineering team designed probiotic bacteria, which in lab mice are shown to deliver and enhance cancer immunotherapy drugs. Researchers at Columbia University in New York describe their engineered bacteria and findings in yesterday’s issue of the journal Science Translational Medicine (paid subscription required).

Treatments that invoke the immune system to attack tumor cells are a major advance in cancer therapy. Checkpoint inhibitors are a key mechanism in these immunotherapy treatments, which block proteins standing in the way of T-cells in the immune system from attacking cancer cells. Among the blocking proteins often targeted by checkpoint inhibitors are programmed cell death–ligand 1, or PDL1, and cytotoxic T lymphocyte–associated protein-4, or CTLA-4.

While cancer immunotherapies with checkpoint inhibitors are successful in attacking some tumors, they have drawbacks. One particular problem, say the authors, is their high rate of adverse side effects found in up to 70 percent of patients, including fatigue, skin rashes, endocrine disorders, and liver toxicity, usually linked to immune-related causes. In addition, immunotherapies can be more effective when given as combinations of treatments, which only increases the risks for adverse effects.

A team from the lab of Columbia biomedical engineering professor Tal Danino is seeking solutions with synthetic biology to make immunotherapies safer for cancer patients, as well as boost their effectiveness. Danino and colleagues alter the genetics of benign bacteria, making it possible to program microbial behavior much like integrated circuits. In the case of cancer treatments, some bacteria are found in tumor tissue, but do not cause infections, thus providing a potential mechanism for cancer drug delivery.

“We wanted to engineer a safe probiotic vehicle capable of delivering immune checkpoint therapies locally to minimize side effects,” says Danino in a university statement. “We also wanted to broaden the versatility of the system by producing a range of immunotherapeutic combinations, including cytokines that could further elicit anti-tumor immunity, but are otherwise difficult to systemically deliver because of toxicity concerns.”

The team led by doctoral candidate and first author Candice Gurbatri took advantage of earlier work with synthetic bacteria designed to lyse, or break down cell membranes, under specified conditions. The previous study, with many of the same authors, found bacteria could be programmed to carry drug molecules, then break apart releasing their cargoes. In this case, the Columbia team started with a benign, probiotic form of E. coli bacteria known as Nissle 1917 that grows inside tumors, to design a drug delivery vehicle.

Using computational models, the researchers altered the Nissle 1917 genome to design a synchronized lysing integrated circuit, or SLIC, strain to carry their drug cargoes. Those cargoes consisted of nanoscale fragments of anti-PDL1 and CTLA-4 checkpoint inhibitors. Tests in lab mice induced with lymphoma and colorectal cancer show a single injection of SLIC bacteria with nanoscale drug fragments into the tumors blocked PDL1 and CTLA-4 proteins, enabling T-cells in the mice to attack the tumors, to a greater extent than antibody injections alone.

The findings show the engineered SLIC bacteria activated more T-cells and caused more tumor shrinkage in the test mice. And as noted by Gurbatri, the treatments spared healthy tissue in mice. “We have demonstrated,” says Gurbatri, “that the engineered bacteria remain functional and localized within the tumor as the bacteria grow in mice for at least two weeks after treatment, preventing the microbes from affecting healthy tissue.”

In 2017, Danino and bioengineering professor Jeff Hasty at University of California in San Diego, founded the company GenCirq Inc. in Santa Barbara, California to commercialize their research in synthetic biology.  The company is developing synthetic lysis circuits for drug delivery.

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Synthetic Cell Matrix Devised for Cancer Drug Testing

Honeycomb scaffold

Scaffold made with electrospun polymer nanofibers in a honeycomb pattern (Smitha Rao, Michigan Tech)

12 Feb. 2020. A bioengineering lab is creating synthetic cell scaffolds that simulate tumor cells and tissue, offering a more reliable way of testing new cancer drugs. Researchers from Michigan Technological University in Houghton describe their process in last month’s issue of the journal IEEE Open Journal of Engineering in Medicine and Biology. The full text is available from the university.

A team led by biomedical engineering professor Smitha Rao is seeking better methods for testing cancer drugs before human clinical trials, to find toxicities or detect other adverse effects, as well as better understand cancer cell growth and migration. Rao’s team, both graduate and undergraduate students, investigated producing simulated cancerous tumor tissue with fine nanoscale polymer fibers, starting with the extracellular matrix or scaffolds, for seeding later with live cancer cells.

“In my lab,” says Rao in a university statement, “the focus has been on standardizing the process and using synthetic materials to keep the same chemical formulation of a scaffold, but change the physical structure of the fibers that are produced.” In the study, the Michigan Tech team altered just one factor, the polymer’s electric field. Otherwise, the researchers maintained the polymer’s nanofiber surface chemistry throughout the study.

The team used a process called electrospinning to create three-dimensional synthetic cell scaffolds.  Electrospinning is a technique that sprays electrically-charged polymer micro- and nanoscale fibers toward a surface, where the fibers form a mat-like structure. The polymer in this case is polycaprolactone or PCL, a bio-compatible and degradable polymer often used in regenerative medicine. In November 2019, Science & Enterprise reported on a portable device that uses electrospinning to spray bio-compatible fibers on simulated wound surfaces to promote healing.

With electrospinning, Rao and colleagues created simulated 3-D tumor tissue scaffolds for different types of breast cancer tumors, using human cancer cell lines. Their tests revealed no one type of scaffold enabled different breast cancer cells to grow into tissue. For example, triple-negative breast cancer cells prefer honeycomb scaffolds, while adenocarcinoma cells, from cancers in mucus-secreting glands, grow better on scaffolds resembling a mesh. And earlier-stage breast tumor cells, before becoming malignant, grow more readily on scaffolds with fibers aligned with each other.

The lab is working with the company DiPole Materials in Baltimore that specializes in electrospinning nanofibers, to scale up the process for industrial and commercial fabrication, such as preclinical drug testing. In the meantime, the Michigan Tech team is exploring ways of applying its cell scaffold process to better understand cancer cell growth and development.

“We can understand in a true 3D system why pre-metastatic cells become metastatic,” notes Rao, “and provide tools to other researchers to study signaling pathways that change between pre-malignant and malignant cells.” Rao tells more about the process in this video.

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