Institute for Biomaterials and Biomedical Engineering

Institute for Biomaterials and Biomedical Engineering

While most people are sheltering at home, it’s more or less business as usual for Professor Warren Chan and his team at the University of Toronto as they rush to develop an automated, more sensitive and rapid test for COVID-19 to help curb the pandemic.

In fact, the current global lockdown has only strengthened the Chan team’s resolve to complete their work. That’s because widespread testing is needed to detect and quickly isolate infected people with mild or no symptoms to halt the novel coronavirus’s rapid spread.

“It is very rewarding being able to work with everyone and do something that is contributing to this and future epidemics,” says Hannah Kozlowski, a graduate student in her fourth year of �鶹ֱ��app’s MD/PhD program.

Powered by tiny light-emitting nanocrystals known as quantum dots, the test can simultaneously detect multiple components of the SARS-CoV-2 genetic material, making it more sensitive than most available methods, which measure only one viral gene at a time. Single tests have a level of uncertainty and can give false negative results in people who are infected.

“A lot of available tests out there are faulty but people are using whatever is available and works best at this point,” says Chan, who is director of �鶹ֱ��app’s Institute of Biomaterials and Biomedical Engineering in the Faculty of Applied Science & Engineering and principal investigator at the Donnelly Centre for Cellular and Biomolecular Research.

“Some of the tests were developed without even being tested on patient samples,” he added, meaning that the tests have not been optimized for variable amounts of the virus across patients.

The project is funded through the $8.4-million Toronto COVID-19 Action Fund, which was launched last month to support high-impact research at �鶹ֱ��app and its partner hospitals in the global fight against the novel coronavirus.

Graduate students working through the lockdown to develop a portable, rapid and sensitive COVID-19 test are pictured in the Donnelly Centre lobby wearing masks and practising physical distancing (photo by Alexandros Sklavounos)

Chan is collaborating with infectious disease specialists in �鶹ֱ��app’s department laboratory medicine and pathbiology in the Faculty of Medicine: Samira Mubareka, who is also with Sunnybrook Health Sciences Centre, and Jonathan Gubbay of Public Health Ontario. The pair are providing patient swab samples from the front line so that the test can be calibrated for clinical use. They previously joined forces in 2016 to develop a test for the Zika virus, but switched their focus to COVID-19 as it began spreading out of China.

The team is also working with Gary Bader, a professor of molecular genetics and computer science in the Donnelly Centre, who is tracking how the virus is evolving so that the test can be adjusted to capture new strains as they appear.

The test is based on quantum dots, nano-scale particles that glow in bright colours when struck by light. These particles can be fitted into microscopic machineries, each looking for signs of the virus while emitting a unique spectrum of light that can be harnessed for test readout. Such collective chemistry produces more data points and serves to increase result confidence.

The test is also rapid, revealing results in under an hour, and it can be carried out outside hospitals or specialized labs. On-the-go testing like this employs a relatively recently developed chemistry in which DNA is amplified at constant temperature unlike the standard method that requires frequent temperature changes obtainable only with specialized instruments.

Matthew Osborne, a second-year graduate student in the lab, is tasked with fitting the entire process – from receiving a swab sample to detecting viral material inside it – into a portable device with a smartphone readout.

“The general idea is that you have a reusable platform that you plug disposable cartridges into, where each cartridge processes a single patient sample,” says Osborne.

“We want the user who’s using the device to have to do the least amount of work as possible,” he says.

The newest member of the lab, Hongmin Chen, who joined the team in January, is taking care of software development.

The device prototype stems from a career marked by deadly outbreaks. SARS was wreaking havoc in Toronto in 2003 soon after Chan joined �鶹ֱ��app as a young faculty member. He set out developing diagnostics with quantum dots, whose application in life sciences researchers were just beginning to explore.

While the device is currently being optimized for the detection of SARS-CoV-2 genetic material, it can also be adapted for antibodies generated in response to the infection to find out who is immune.

“We have been putting this in place for 18 years,” says Chan. “We took the time to develop all the science behind it and now we have a plug-and-play system that can be applied for various applications,” he says.

The team collectively made the decision to continue working on their COVID-19 project during lockdown, obtaining special permission from the university.

“It’s a project that we’ve already been working on and the pandemic has really pushed us to improve and hopefully make an impact sooner,” Osborne says.

�鶹ֱ��app precision medicine initiative launches task force to fight COVID-19

Christopher.Sorensen — Fri, 17 Apr 2020 15:38:10 +0000

�鶹ֱ��app precision medicine initiative launches task force to fight COVID-19

Christopher.Sorensen Fri, 04/17/2020 - 11:38

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The PRiME Task Force on Advanced Diagnostics and Therapeutics for COVID-19 brings together �鶹ֱ��app researchers with expertise in a variety of fields to develop new diagnostic tools and therapeutics (photo by Steve Southon)

Topic

Faculty of Arts & Science

Institute for Biomaterials and Biomedical Engineering

Leslie Dan Faculty of Pharmacy

The University of Toronto’s precision medicine research initiative, PRiME, has launched a new task force mobilizing research to tackle the immense challenge of the COVID-19 pandemic.

Led by University Professor Shana Kelley from the Leslie Dan Faculty of Pharmacy, the PRiME Task Force on Advanced Diagnostics and Therapeutics for COVID-19 brings together researchers with expertise in a variety of fields to develop new diagnostic tools and therapeutics.

“Biomedical research is absolutely critical to how we combat and recover from these types of crises,” Kelley says. “The key tools that are going to help us with this pandemic and those that arise in the future are better diagnostics, new therapies and vaccines. This is what the biomedical research community has to offer.”

Launched in the spring of 2019, PRiME taps into �鶹ֱ��app’s world-class research – in the Faculty of Pharmacy, Faculty of Medicine, Faculty of Arts & Science and Faculty of Applied Science & Engineering – and fosters collaborations to address large-scale research questions. With more than 60 scientists and 100 students and trainees aligning their efforts in a few key areas of precision medicine research, PRiME is meant to accelerate the discovery of new tools to diagnose and treat a number of diseases.

“If something is going to make an impact on the first wave of COVID-19, it needs to go into the clinic within the coming weeks,” says University Professor Shana Kelley, who is leading the task force (photo by Steve Southon)

Now, they are turning their attention to an urgent global health challenge. As the scale of the COVID-19 outbreak became apparent over the last couple of months, Kelley, along with Associate Director Stéphane Angers and Director of Strategy and Partnerships Christine Misquitta, talked to PRiME members about their research plans and potential projects related to COVID-19.

“These are people who can’t stop thinking about scientific research and how it may be applied to monitor and treat diseases,” says Kelley. “So, when something like this comes up, it’s very natural for us to think about ways that we can pivot our research operations and try to make an impact.”

The resulting research plan is a grassroots effort by the researchers and has three objectives: produce new diagnostic tools, develop new therapeutics and understand the biology of the novel coronavirus and COVID-19. PRiME scientists are actively collaborating with colleagues based at �鶹ֱ��app’s affiliated hospitals including the Sunnybrook Health Sciences Centre and the Hospital for Sick Children.

Many of the task force’s research projects have already begun – with precautions to ensure physical distancing and safe work conditions – and research teams will work closely with clinicians in order to have results translated into the clinic in a relatively short time frame. New diagnostic tools could be approved by Health Canada by early summer through an expedited review process, and researchers looking for new therapeutics are focusing on U.S Food and Drug Administration- or Health Canada-approved agents so that they can be deployed quickly.

“If something is going to make an impact on the first wave of COVID-19, it needs to go into the clinic within the coming weeks,” says Kelley. “It’s difficult to take something from research to clinic in that amount of time, but we do have researchers fast-tracking their efforts on a relevant timescale.”

Leo Chou, assistant professor in the Faculty of Applied Science & Engineering and a member of the task force, is using his team’s expertise in computational design, materials chemistry and molecular engineering to increase capacity to test people for the virus. His team is working on a new streamlined diagnostic test that uses nucleic acids to help detect viral RNA to provide an alternative and more stable set of reagents relative to the enzymes used in current diagnostic tests. They are working to minimize the number of steps involved in the test and find ways to couple the detection of viral RNA with a material change, such as a change in colour, that would make it easier to see test results with the naked eye. These developments would make testing faster and easier to do – both of which would increase testing capacity.

As a researcher working in basic science, Chou says that initiatives such as PRiME and the task force are essential to accessing resources that can move research forward more quickly.

“One bottleneck to many developing efforts right now is access to patient samples,” he says. “A platform such as PRiME is in a unique position to co-ordinate large resource-sharing centres where members can deposit, share and access common reagents, protocols and knowledge related to COVID-19 detection and treatment.”

Kelley says that she has been encouraged by the response from PRiME researchers, as even those with no expertise related to coronaviruses have thought about how their research can reduce the impact of COVID-19 during this unprecedented challenge.

“This is just a completely different way of doing science. As researchers with deep expertise in specific disciplines, we don’t typically pivot to new areas like this,” she says. “But I think so many of us have realized that we have the biggest crisis of our lifetime on our hands, and we need to be helping to find a solution now.”

�鶹ֱ��app researchers show how a protein found in cardiac muscle helps prevent heart failure

Christopher.Sorensen — Thu, 20 Feb 2020 15:37:56 +0000

�鶹ֱ��app researchers show how a protein found in cardiac muscle helps prevent heart failure

Christopher.Sorensen Thu, 02/20/2020 - 10:37

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From left to right: Harsha Murthy, Frank Shin-Haw Lee and Sina Hadipour-Lakmehsari (photo by Jim Oldfield)

�鶹ֱ��app Medicine

Topic

Dalla Lana School of Public Health

Hospital for Sick Children

Institute for Biomaterials and Biomedical Engineering

Molecular Genetics

Ted Rogers Centre for Heart Research

University Health Network

Researchers at the University of Toronto have found that a receptor expression-enhancing protein contributes to normal heart development and function by regulating the sarcoplasmic reticulum, a network of tubules found in cardiac muscle cells.

The sarcoplasmic reticulum is key in the development and progression of heart disease, governing biochemical changes, structural remodeling and deterioration. But how this membrane-bound system organizes itself is still mostly unknown – especially in cells with a highly differentiated or diverse network such as heart muscle cells, or cardiomyocytes.

“Our findings show that a protein called REEP5 plays a critical role in regulating cellular stress responses in heart muscle cells,” says Frank Shin-Haw Lee, a PhD student in the lab of Anthony Gramolini, an associate professor of physiology in �鶹ֱ��app’s Faculty of Medicine who is based at the Ted Rogers Centre for Heart Research.

“When REEP5 is depleted, it destabilizes the heart and reduces the amount of blood the heart can pump on each contraction,” says Lee. “When we removed this protein in both mice and zebrafish, it distorted the structure and shape of cardiomyocytes and led to cardiac dysfunction.”

The journal Nature Communications published the findings this week.

When cardiomyocytes are under sustained stress from general dysfunction or disease, cellular pathways through the sarcoplasmic reticulum can lead to cell death and heart failure. Lee says that REEP5 is vital to the formation of the sarcoplasmic reticulum and to how it responds to stress and regulates calcium, which is essential for heart health.

A better understanding of how REEP5 functions in the heart may elucidate how heart failure develops amidst a sarcoplasmic reticulum in stress, Lee says.

The Gramolini lab worked with several other Toronto researchers on the study, including Ian Scott, a professor of molecular genetics at �鶹ֱ��app and a senior scientist at the Hospital for Sick Children. The work builds on previous collaborative research from the labs of Gramolini, Scott and medical biophysics professor Thomas Kislinger in 2015, which created a blueprint of critical cell-surface and membrane-associated proteins in the heart.

Medical student Sina Hadipour-Lakmehsari was a co-first author on the current paper with Lee, and he says the findings may provide insight into heart disease in patients.

“It is clearly an important protein for cardiac development and function and, combined with future human studies, it may help us unearth new potential therapies,” Hadipour-Lakmehsari says, adding that the lab can continue to look at REEP5 in genetic studies to help shed light on diseases whose causes remain unknown.

“This study is among the first in the world to show that the REEP5 protein plays an essential role in the stress responses that often lead to heart failure,” adds Gramolini, who is also a scientist at Toronto General Hospital Research Institute, University Health Network. “Deciphering the complex layers of heart function on a cellular level will help us generate new therapeutic and preventative strategies for heart failure.”

The study received support from the Ted Rogers Centre Innovation Fund, the Natural Sciences and Engineering Research Council of Canada and the Canadian Institutes of Health Research, among others.

Paired with a smartphone, pill-sized 'heater' developed at �鶹ֱ��app could be used to diagnose infectious disease

Christopher.Sorensen — Wed, 19 Feb 2020 14:58:07 +0000

Paired with a smartphone, pill-sized 'heater' developed at �鶹ֱ��app could be used to diagnose infectious disease

Christopher.Sorensen Wed, 02/19/2020 - 09:58

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�鶹ֱ��app researchers Buddhisha Udugama (left) and Pranav Kadhiresan show off a tiny lithium heater, which regulates the temperature of biological samples through different stages of diagnostic testing – crucial for accurate results (photo by Qin Dai)

Qin Dai

Topic

Donnelly Centre for Cellular & Biomolecular Research

Institute for Biomaterials and Biomedical Engineering

Researchers at the University of Toronto have developed a tiny “heater” – about the size of a pill – that could allow resource-limited regions around the world to test for infectious diseases without the need for specialized training or costly lab equipment.

The technology, developed by researchers in the Faculty of Applied Science & Engineering, regulates the temperature of biological samples through different stages of diagnostic testing, which is crucial to the accuracy of test results.

“The precision and flexibility of our heater opens the door to a future of do-it-yourself diagnostic kits,” says Pranav Kadhiresan, who developed the device alongside Buddhisha Udugama.

“We could combine the simplicity of a high school chemistry set with the precision of cutting-edge lab instruments.”

Both researchers are PhD candidates at the Institute of Biomaterials and Biomedical Engineering (IBBME) and the Donnelly Centre who are supervised by Warren Chan, a professor at both the Donnelly Centre and IBBME. The technology behind the team’s miniaturized heater invention is described in a paper published in the journal of Proceedings of the National Academy of Sciences.

In a typical diagnostic test for infectious pathogens, multiple temperature-regulation steps are involved. The ability to control temperature is especially important in areas where access to large research facilities are limited.

“The lack of electricity adds a layer of complexity,” says Udugama. “Our miniature heater addresses that. It can be used in various settings to detect viruses without the need for electricity. If we were to summarize the benefits of our technology, it would be accessibility, portability and precision.”

The outside of the heater tablet is composed of a non-reactive acrylic mould that encapsulates lithium, a reactive element that is commonly found in battery cells. When dissolved in water, the reactive lithium interacts with the solution to release heat and hydrogen gas. This results in an increase of temperature for an extended period of time.

The researchers observed that the reproducibility of the temperature profile is controlled by constant gas release, which is dictated by the shape of the lithium mould. After testing multiple shapes of the lithium mould – from circles to triangles – they found the star shape, measuring just eight millimetres in diameter, to be ideal for precise heating.

Consolidating multiple steps into a single tablet also means specialized training is not required to operate any diagnostic testing, reducing the chance of human error and making the device accessible to the public.

“Tablets are conventionally used for medications such as aspirins. But we have now developed a series of tablets and pills that can diagnose diseases,” says Chan, who was the principal investigator on this research and is the director of IBBME.

“Combined with smartphone technology, everyone would have a portable system that can track, monitor and diagnose infections. This is critical for preventing the spread of diseases.”

The research received support fom the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada, among others.

Most engineered nanoparticles enter tumours through cells – not between them, �鶹ֱ��app researchers find

Christopher.Sorensen — Tue, 14 Jan 2020 17:51:31 +0000

Most engineered nanoparticles enter tumours through cells – not between them, �鶹ֱ��app researchers find

Christopher.Sorensen Tue, 01/14/2020 - 12:51

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The solid arrows show nanoparticles (the dark spots) being engulfed by endothelial cells, not passing through gaps between the cells – a finding that could change the way researchers think about delivering drugs to tumours (image via Nature Materials)

Jim Oldfield

Qin Dai

Topic

Donnelly Centre for Cellular & Biomolecular Research

Faculty of Arts & Science

Institute for Biomaterials and Biomedical Engineering

Physics

University of Toronto researchers have discovered that an active rather than passive process dictates which nanoparticles enter solid tumours, upending decades of thinking in the field of cancer nanomedicine and pointing toward more effective nanotherapies.

The prevailing theory in cancer nanomedicine – an approach that enables more targeted therapies than standard chemotherapy – has been that nanoparticles mainly diffuse passively into tumours through tiny gaps between cells in the endothelium, which lines the inner wall of blood vessels that support tumour growth.

The researchers previously showed that less than one per cent of nanoparticle-based drugs typically reach their tumour targets. In the current study, they found that among nanoparticles that do penetrate tumours, more than 95 per cent pass through endothelial cells – not between gaps among those cells.

“Our work challenges long-held dogma in the field and suggests a completely new theory,” says Abdullah Syed, a co-lead author on the study and post-doctoral researcher in the lab of Warren Chan, a professor at the Institute of Biomaterials and Biomedical Engineering and the Donnelly Centre for Cellular and Biomolecular Research.

“We saw many nanoparticles enter the endothelial cells from blood vessels and exit into the tumour in various conditions. Endothelial cells appear to be crucial gatekeepers in the nanoparticle transport process.”

The findings were recently published in the journal Nature Materials.

From left to right: �鶹ֱ��app researchers Jessica Ngai, Shrey Sindhwani, Abdullah Syed and Benjamin Kingston (photo by Qin Dai)

Syed compares nanoparticles to people trying to get into popular restaurants on a busy night. “Some restaurants don’t require a reservation, while others have bouncers who check if patrons made reservations,” he says. “The bouncers are a lot more common than researchers thought, and most places only accept patrons with a reservation.”

The researchers established that passive diffusion was not the mechanism of entry with multiple lines of evidence. They took over 400 images of tissue samples from animal models and saw few endothelial gaps relative to nanoparticles. They observed the same trend using 3D fluorescent imaging and live-animal imaging.

Similarly, they found few gaps between endothelial cells in samples from human cancer patients.

The group then devised an animal model that completely stopped the transportation of nanoparticles through endothelial cells. This allowed them to isolate the contribution of passive transport via gaps between endothelial cells, which proved to be miniscule.

The researchers posit several active mechanisms by which endothelial cells might transport nanoparticles into tumours, including binding mechanisms, intra-endothelial channels and as-yet undiscovered processes – all of which they are investigating.

Meanwhile, the results have major implications for nanoparticle-based therapeutics.

“These findings will change the way we think about delivering drugs to tumours using nanoparticles,” says Shrey Sindhwani, also a co-lead author on the paper and an MD/PhD student in the Chan lab. “A better understanding of the nanoparticle transport phenomenon will help researchers design more effective therapies.”

The research included collaborators from �鶹ֱ��app’s department of physics in the Faculty of Arts & Science, Cold Spring Harbor Laboratory In New York and the University of Ottawa. The study was funded by the Canada Research Chairs Program, Canadian Cancer Society, Natural Sciences and Engineering Research Council of Canada and the Canadian Institutes of Health Research.

A diabetes drug promotes brain repair – but only in females, �鶹ֱ��app study shows

Christopher.Sorensen — Thu, 12 Sep 2019 14:49:05 +0000

A diabetes drug promotes brain repair – but only in females, �鶹ֱ��app study shows

Christopher.Sorensen Thu, 09/12/2019 - 10:49

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Cindi Morshead (centre) and graduate students Rebecca Ruddy (left) and Kelsey Adams. The study by Morshead's team highlights how sex bias in preclinical work can lead to failed clinical trials and inappropriate treatments (photo by Jovanna Drinjakovic)

Jovana Drinjakovic

Topic

Donnelly Centre for Cellular & Biomolecular Research

Hospital for Sick Children

Global

Institute for Biomaterials and Biomedical Engineering

surgery

Males are straightforward while females are complicated. This misguided view prompted a decades-long exclusion of female animals from research out of fear that their fluctuating hormone levels will muddle the data.

But now a new study by researchers at the University of Toronto shows that a female sex hormone plays a key role in promoting brain repair and opens the door to the development of more effective treatments.

The team of researchers led by Cindi Morshead, a professor at the Donnelly Centre for Cellular and Biomolecular Research and the department of surgery, found that metformin, a widely prescribed drug to treat diabetes, promotes repair in adult female brains and is dependent on the sex hormone estradiol.

Their findings are described in a study published in the Sept. 11, 2019 issue of the journal Science Advances.

The research builds on a previous study, in collaboration with Freda Miller’s group at the Hospital for Sick Children, that sought to find treatment for childhood brain injury. They found that the widely prescribed drug metformin can induce brain repair and improve motor function in newborn mice that had a stroke injury. Metformin works by activating stem cells in the brain, which can self-renew and give rise to different types of brain cells to replace those killed by injury.

Because brain injury in early life can lead to lifelong cognitive problems, the researchers wanted to find out if metformin also promoted cognitive recovery.

“You can fix a hole in someone’s brain, but if they don’t function better it’s irrelevant to them,” says Morshead, who is also a professor at �鶹ֱ��app’s Institute of Medical Science and the Institute of Biomaterials and Biomedical Engineering.

Graduate student Rebecca Ruddy induced stroke in newborn mice, followed by daily metformin treatment before the animals were tested in a puzzle box test that measured learning and memory.

The metformin was able to activate neural stem cells in the brain and promote cognitive recovery. But the data also revealed something unexpected: Metformin did not affect all the animals in equal manner. It only worked in adult females.

“When we first looked at the data, we did not see the benefit of the metformin treatment,” says Morshead. “Then we noticed that adult females tended to do better than the males.”

A closer look revealed that metformin selectively activated the adult female neural stem cells while having no effect on the males. This turned out to be due to the female sex hormone estradiol which somehow enhances the stem cells’ ability to respond to metformin. Conversely, the male hormone testosterone appears to inhibit this process. When female mice had their ovaries removed and lacked the female sex hormone, the stem cells did not respond to metformin treatment.

“To know that there are both age and sex dependent effects – it has such implications for treatment and therapeutics,” says Morshead.

The findings come at a time when the research community is reckoning with the data sex bias stemming from an overwhelming exclusion of female mice from research.

“The thinking was that we’re going to study males because everything you need to know is found in the male brain, and then the female brain just complicates things with hormones,” says Morshead. “It’s very misguided and troublesome for advancing neurological health.”

As preclinical research informs human studies, the sex bias is believed to have led to failed clinical trials, misdiagnosis and inappropriate therapies for women, as highlighted in a recent article in Science.

Human trials focused on repurposing metformin as a brain repair drug are ongoing. Morsehead’s collaborators – Dr. Donald Mabbott, the head of neurosciences and mental health at SickKids, and Dr. Eric Bouffet, the director of the brain tumour program at SickKids – are leading a pilot study testing the drug in children who suffered brain injury. Although the current patient cohort is too small to detect any sex effects, the plan is to increase the number of patients to see if sex also affects treatment outcome in people, Morshead says.

The research was supported by the funding from the Canadian Institutes of Health Research, which in 2016 mandated its grant holders to consider animals of both sexes in their research, as well as from the Ontario Institute for Regenerative Medicine, Medicine by Design, Brain Canada, the Stem Cell Network and the Ontario Brain Institute.

German multinational buys part of �鶹ֱ��app spin-off company that makes medical implants safer

Christopher.Sorensen — Tue, 03 Sep 2019 15:15:14 +0000

German multinational buys part of �鶹ֱ��app spin-off company that makes medical implants safer

Christopher.Sorensen Tue, 09/03/2019 - 11:15

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�鶹ֱ��app Professor Paul Santerre spun off Interface Biologics in 2001 to commercialize research that reduced blood clots and infections associated with medical implants (photo by Chris Sorensen)

Tyler Irving

Topic

Global Lens

Entrepreneurship

Institute for Biomaterials and Biomedical Engineering

Faculty of Dentistry

Global

Health Innovation Hub

Startups

Nearly 20 years ago, Paul Santerre and his team pioneered a new way of making medical implants that reduces the risk of blood clots and infections. Now, the technology is set to go global after being acquired by Evonik, a multinational specialty chemicals firm that plans to maintain a presence in Toronto.

The spin-off company created through Santerre’s research – Interface Biologics Inc. (IBI) – said on Tuesday that its surface modification division will be acquired by Germany’s Evonik for an undisclosed sum.

“This is a professor’s dream,” says Santerre, a professor in the University of Toronto’s Faculty of Dentistry with a cross-appointment at the Institute of Biomaterials and Biomedical Engineering.

“It’s the best outcome for our startup: investment, sales and drawing a major company here to do product development.”

Active in over 100 countries around the world, Evonik has more than 32,000 employees who last year generated more than $21.4 billion in sales.

From catheters to artificial hips, implants are a critical component of modern health care. But the surfaces of such devices can become a habitat for infectious bacteria. They can also trigger the body’s natural responses, creating life-threatening blood clots that are released through a process known as thrombosis.

Santerre’s technology works by modifying the surface of materials implanted in the body. These modifications make it more difficult for certain proteins – such as those that cause blood clots, whether secreted by invading bacteria, blood platelets or blood cells – to stick to the surface.

At the heart of the innovation is a series of short-chain molecules called oligomers. Like another famous non-stick material, Teflon, the oligomers that Santerre conceived contain fluorine as part of their chemical structure.

But whereas Teflon must be spray-coated onto a surface after it’s made, Santerre’s additives can be mixed directly into molten plastic. As the plastic cools, the oligomers migrate to the top few nanometres, creating a non-stick surface without the need for any additional manufacturing steps.

In 2001, the technology, branded Endexo, was part of a suite of innovations that was used to form IBI.

“We are excited to onboard the Endexo technology in our portfolio,” Jean-Luc Herbeaux, the senior vice-president and general manager of Evonik’s health care business, said in a statement.

“Endexo expands our ability to serve as a development partner and solution provider to medical device companies worldwide. The team of Interface Biologics has done an exemplary job developing this innovative technology and bringing it to market. We look forward to applying our global business development capabilities and technical prowess to further expand the geographic and application footprint of Endexo.”

The IBI team will support Evonik’s continuity of the business under a two-year transition services agreement. Evonik is expected to build on IBI’s expertise in surface modification by maintaining a presence in Toronto.

“Evonik was impressed not only by the IBI story, but by the rich and growing innovation ecosystem across �鶹ֱ��app, and Toronto more generally,” says Santerre, who is also a co-director of �鶹ֱ��app’s Health Innovation Hub (H2i), one of several entrepreneurship hubs on campus.

Santerre says that the new deal will take the technology to larger markets faster than would have been possible with IBI. But he is even more excited by what this means for the future of entrepreneurship and commercialization at �鶹ֱ��app.

“Evonik is now the second major multinational health technology company to want to live here,” he says. “They will likely catalyze many more to come.”

Not all stem cells are created equal, �鶹ֱ��app study reveals

noreen.rasbach — Thu, 21 Mar 2019 17:56:24 +0000

Not all stem cells are created equal, �鶹ֱ��app study reveals

noreen.rasbach Thu, 03/21/2019 - 13:56

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This illustration by Jen Ma, a PhD candidate at �鶹ֱ��app, depicts competition between a population of cells. “Elite” cells appear to outcompete their neighbours in the process of becoming stem cells

Qin Dai

Topic

Donnelly Centre for Cellular & Biomolecular Research

Institute for Biomaterials and Biomedical Engineering

Molecular Genetics

Regenerative Medicine

Researchers from the University of Toronto's Institute for Biomaterials and Biomedical Engineering (IBBME) and the Donnelly Centre have discovered a population of cells – dubbed to be “elite” – that play a key role in the process of transforming differentiated cells into stem cells. The finding has important implications for regenerative medicine.

Stem cells have the ability to transform into specialized cells – from lung to brain. Stem cells are common in embryos, but within the last 15 years, a technique called cell reprogramming has enabled scientists to turn mature cells back into so-called pluripotent stem cells, with the power to develop into any cell type. The technique was recognized with the Nobel Prize in 2012.

While reprogramming is well understood, less is known about the intricacies of how individual reprogramming cells behave in a population setting. University Professor Peter Zandstra’s group (he is a dual appointment at �鶹ֱ��app and the University of British Columbia) recently led a study examining this, and found a group of cells that appear to have a competitive advantage in reprogramming. The research is published today in Science.

Zandstra and his team used cells extracted from mouse skin, known as mouse embryonic fibroblasts (MEFs). They used DNA-barcoding technologies to give each MEF a unique tag, track individual cells during reprogramming and associate them with their parent population. They also used computational modelling to help understand the complex data generated and to make predictions that were tested in the lab.

The team found that up to 80 per cent of the original cell population was eliminated after one week of reprogramming. Only a small percentage of the parent generation was fit enough to propagate their clones and turn into stem cells during the stressful reprogramming process. Although these cells have a similar genetic makeup and outward appearance compared to their siblings, their higher fitness enabled them to produce more progeny, that is, clone themselves with greater frequency. The team called these cells “elite clones.”

“Cell fitness is, broadly speaking, the ability of a cell to outcompete its neighbors either directly or indirectly,” says Nika Shakiba, who completed her doctoral studies at the Donnelly Centre and is the lead author of the article.

“There’s direct elimination, where one cell can engulf another one or release chemicals that trigger its death. But there is also indirect competition where cells compete for a pool of limited nutrients and space on the petri dish. It’s analogous to similar sorts of competition in ecology.”

The new finding speaks to a debate within the stem cell community. Some researchers believe that all cells have the capacity to be reprogrammed into an embryonic stem cell-like state, while others believe that only a specific subset of cells have this elite ability. Shakiba says that while there is evidence on both sides, the latest study favours the latter explanation.

“(Our study) challenges people to look at the reprogramming phenomenon through the lens of clonal dynamics – how clones composing a multicellular population compete and how this influences the overall population,” she says.

Zandstra’s team collaborated with Derek van der Kooy, a professor of molcular genetics located in the Donnelly Centre. By using a mouse model developed by co-lead author Ahmed Fahmy, a graduate student of molecular genetics, the authors were able to find a lineage of MEFs that exhibit the properties of “elite clones” discovered by Shakiba. These cells originate from a part of the embryo known as the neural crest, which play a key role in the development of skin, neuronal and smooth muscle cells. The researchers hypothesize that the neural crest cells are "fated to be fit."

“They're lucky and therefore they get a head start in the reprogramming race,” says Shakiba. “By getting to that pre-programmed state earlier, they are going to divide faster than their competitors. After a few generations, that initial head start becomes much bigger.”

This study was a result of an interdisciplinary effort between Toronto researchers, bringing together the labs of Jeffrey Wrana (Lunenfeld-Tanenbaum Research Institute), who made key contributions to the barcoding platform and studies; Sidhartha Goyal, who led computational modeling efforts; van der Kooy, who led the neural crest lineage tracing efforts; and Andras Nagy (Lunenfeld-Tanenbaum Research Institute), who developed mouse reprogramming lines.

The findings in this paper also have significant implications for regenerative medicine, including techniques where stem cells are used to create specific tissues that are then implanted into the body to repair damage.

“Let’s say we want to inject a stem cell population into the body to regenerate the heart,” says Shakiba. “The ability of those injected cells to survive and integrate into native tissues depends on the competitive ability – the fitness – of those cells. Unless we have an understanding and appreciation for how these cells will compete, not only with one another but with the endogenous cells that we are now injecting them into, we are not going to be able to really predict or control what they're going to do in the body.”

“I am really excited about this study because it teaches us a number of new fundament things,” says Zandstra. “Ultimately, it teaches us that cell competition is a controllable parameter that can be engineered to influence the outcome of dynamic regenerative processes.

"This finding should lead to new strategies and technologies to repopulate tissue in vivo post stem-cell transplantation, or to identify ways to make cells more susceptible to competition in clonal diseases such as cancer.”

The research was supported by Medicine by Design, the Canadian Institutes of Health Research and Canada First Research Excellence Fund program funding.

New way of growing cancer cells, developed at �鶹ֱ��app, could speed up the search for new drug treatments

noreen.rasbach — Mon, 25 Feb 2019 17:32:53 +0000

New way of growing cancer cells, developed at �鶹ֱ��app, could speed up the search for new drug treatments

noreen.rasbach Mon, 02/25/2019 - 12:32

Cutline

The 3D hydrogel created in University Professor Molly Shoichet’s lab was modelled to mimic the environment of lung cancer, enabling more effective and quicker drug screening (photo by Roberta Baker)

Liz Do

Topic

Donnelly Centre for Cellular & Biomolecular Research

Cancer

Institute for Biomaterials and Biomedical Engineering

Global

Molly Shoichet