Connect with us

News

Reverse engineering the heart: University of Toronto Engineering team creates bioartificial left ventricle

Published

on

bioartificial left ventricle

University of Toronto Engineering researchers have grown a small-scale model of a human left heart ventricle in the lab. The bioartificial tissue construct is made with living heart cells and beats strongly enough to pump fluid inside a bioreactor.

In the human heart, the left ventricle is the one that pumps freshly oxygenated blood into the aorta, and from there into the rest of the body. The new lab-grown model could offer researchers a new way to study a wide range of heart diseases and conditions, as well as to test out potential therapies.

“With our model, we can measure ejection volume — how much fluid gets pushed out each time the ventricle contracts — as well as the pressure of that fluid,” says Sargol Okhovatian. “Both of these were nearly impossible to get with previous models.”

Okhovatian and Mohammad Hossein Mohammadi are co-lead authors on a new paper in Advanced Biology that describes the model they designed. Their multidisciplinary team was led by Professor Milica Radisic, senior author of the paper.

All three researchers are members of the Centre for Research and Applications in Fluidic Technologies (CRAFT). A unique partnership between Canada’s National Research Council and the University of Toronto, CRAFT is home to world-leading experts who design, build and test miniaturized devices to control fluid flow at the micron scale, a field known as microfluidics.

“The unique facilities we have at CRAFT enable us to create sophisticated organ-on-a-chip models like this one,” says Radisic.

“With these models, we can study not only cell function, but tissue function and organ function, all without the need for invasive surgery or animal experimentation. We can also use them to screen large libraries of drug candidate molecules for positive or negative effects.”

Many of the challenges facing tissue engineers relate to geometry: while it’s easy to grow human cells in two dimensions — for example, in a flat petri dish — the results don’t look much like real tissue or organs as they would appear in the human body.

To move into three dimensions, Radisic and her team use tiny scaffolds made from biocompatible polymers. The scaffolds, which are often patterned with grooves or mesh-like structures, are seeded with heart muscle cells and left to grow in a liquid medium.

Over time, the living cells grow together, forming a tissue. The underlying shape or pattern of the scaffold encourages the growing cells to align or stretch in a particular direction. Electrical pulses can even be used to control how fast they beat — a kind of training gym for the heart tissue.

For the bioartificial left ventricle, Okhovatian and Mohammadi created a scaffold shaped like a flat sheet of three mesh-like panels. After seeding the scaffold with cells and allowing them to grow for about a week, the researchers rolled the sheet around a hollow polymer shaft, which they call a mandrel.

The result: a tube composed of three overlapping layers of heart cells that beat in unison, pumping fluid out of the hole at the end. The inner diameter of the tube is 0.5 millimetres and its height is about 1 millimetre, making it the size of the ventricle in a human fetus at about the 19th week of gestation.

“Until now, there have only been a handful of attempts to create a truly 3D model of a ventricle, as opposed to flat sheets of heart tissue,” says Radisic.

“Virtually all of those have been made with a single layer of cells. But a real heart has many layers, and the cells in each layer are oriented at different angles. When the heart beats, these layers not only contract, they also twist, a bit like how you twist a towel to wring water out of it. This enables the heart to pump more blood than it otherwise would.”

The team was able to replicate this twisting arrangement by patterning each of their three panels with grooves at different angles to each other.

In collaboration with Professor Ren-Ke Li’s lab within the University Health Network, they measured the ejection volume and pressure using a conductance catheter, the same tool used to assess these parameters in living patients.

At the moment, the model can only produce a small fraction — less than 5% — of the ejection pressure that a real heart could, but Okhovatian says that this is to be expected given the scale of the model.

“Our model has three layers, but a real heart would have eleven,” she says.

“We can add more layers, but that makes it hard for oxygen to diffuse through, so the cells in the middle layers start to die. Real hearts have vasculature, or blood vessels, to solve this problem, so we need to find a way to replicate that.”

Okhovatian says that in addition to the vasculature issue, future work will focus on increasing the density of cells in order to increase the ejection volume and pressure. She also wants to find a way to shrink or eventually remove the scaffold, which a real heart wouldn’t have.

Though the proof-of-concept model represents significant progress, there is still a long way to go before fully functional artificial organs are possible.

“We have to remember that it took us millions of years to evolve a structure as complex as the human heart,” says Radisic.

“We’re not going to be able reverse engineer the whole thing in just a few years, but with each incremental improvement, these models become more useful to researchers and clinicians around the world.”

“The dream of every tissue engineer is to grow organs that are fully ready to be transplanted into the human body,” Okhovatian.

“We are still many years away from that, but I feel like this bioartificial ventricle is an important stepping-stone.”

Continue Reading

News

Narwhals show physiological disruption in response to seismic survey ship noise

Published

on

physiological disruption

The reaction of narwhals to the loud noise from seismic air guns used in oil exploration involves a disruption of the normal physiological response to intense exercise as the animals try to escape the noise. The overall effect is a large increase in the energetic cost of diving while a paradoxically reduced heart rate alters the circulation of blood and oxygen.

“They’re swimming as hard as they can to get away, and yet their heart rate is not increasing—we think because of a fear response. This affects how much blood and oxygen can circulate, and that’s going to be problematic,” said Terrie Williams, a professor of ecology and evolutionary biology at UC Santa Cruz who led the new study.

Published July 8 in the Journal of Functional Ecology, the study provides the first look at the impact of seismic noise on the physiological responses of a deep-diving cetacean. According to Williams, the combination of extremely low heart rates, increased heart rate variability, and high-intensity exercise during deep dives presents a significant physiological challenge for narwhals, especially if the disruptions are prolonged as would be likely during extended oil exploration activities.

Narwhals live year-round in high Arctic waters where sea ice has helped isolate them from disturbance by humans for millions of years. But declines in polar sea ice are making the region more accessible to shipping, natural resource exploration, and other human activities.

In a previous study, Williams and her coauthors showed that narwhals released after entanglement in nets set by indigenous hunters showed a similar physiological response, with extremely low heart rates during intense exercise in a series of escape dives. The difference between a capture event and noise, Williams said, is the potential duration of the disturbance.

“When they escape from the nets, their heart rate comes back up to a more normal rate within three or four dives, but with the seismic ship moving through and the sound bouncing around, the escape response occurred over a longer period,” she said.

The researchers recorded not only extremely low heart rates during noise exposure, but also increased variability, with heart rates switching rapidly between extremely low rates associated with fear and fast rates associated with intense exercise. Reduced heart rate, or bradycardia, is a normal part of the mammalian dive response, but during normal dives the heart rate still increases with exercise. In addition, narwhals and other deep-diving marine mammals usually save energy by gliding rather than actively swimming as they descend to depth.

During noise exposure, the narwhals performed 80% less gliding during diving descents, their swimming strokes exceeded 40 strokes per minute, their heart rates dropped below 10 beats per minute, and their breathing at the surface was 1.5 times faster. Overall, this unusual reaction is very costly in terms of energy consumption, Williams said.

“Not only is the reaction costly in terms of the energy needed for diving, the escape time will also take away from time spent foraging for food and other normal behaviors,” she said.

The studies were conducted in Scoresby Sound on the east coast of Greenland, where coauthor Mads Peter Heide-Jørgensen, a research professor at the Greenland Institute of Natural Resources, has been studying the East Greenland narwhal population for more than a decade.

Williams’s group at UC Santa Cruz developed instruments that enable researchers to monitor the exercise physiology of marine mammals during dives. The instruments were attached to narwhals with suction cups and fell off after one to three days, floating to the surface where they could be recovered by the scientists.

Over the past two decades, noise from human activities such as military sonar has been linked to mass strandings of deep-diving cetaceans, mostly beaked whales. These deep-diving species are extremely difficult to study, and it was only through a partnership with indigenous hunters that Williams and Heide-Jørgensen’s teams were able to attach monitoring devices to narwhals.

“Most of the potential impacts on the animals take place underwater, so it’s really difficult to study,” Williams said. “We are fortunate to have this technology to show what’s happening at depth where these animals live in order to understand how their biology may be disrupted.”

In addition to Williams and Heide-Jørgensen, the coauthors of the paper include Susan Blackwell at Greeneridge Sciences, Outi Tervo and Eva Garde at the Greenland Institute of Natural Resources, Mikkel-Holger Sinding at University of Copenhagen, and Beau Richter at UC Santa Cruz. This work was supported by the U.S. Office of Naval Research, Greenland Institute of Natural Resources, the Environmental Agency for Mineral Resource Activities of the Government of Greenland, the Danish Ministry of Environment, and the Carlsberg Foundation.

Continue Reading

News

New robotics image processing tools help automate aircraft surface preparation

Published

on

robotics

Researchers at the Southwest Research Institute will be introducing new automation technology that will enable automation of aircraft surface preparation. The tools basically allow industrial robots to visually classify work and autonomously perform tasks.

SwRI’s Automate Booth (No. 1707) will feature an interactive demonstration of robots that autonomously sand and prepare surfaces on aircraft and other machinery. The technology can be applied to grinding, painting, polishing, cleaning, welding, sealing and other industrial processes.

The system uses SwRI-developed machine learning algorithms and classification software that work in conjunction with open-source tools such as Scan-N-PlanTM and ROS 2, the latest version of the open-source robot operation system. Traditional robot programming can be slow and tedious, requiring an expert in the loop with knowledge of computer aided design (CAD).

Scan-N-Plan, a ROS-Industrial technology, uses machine vision to scan parts, creating 3D mesh data that robots use to plan tool paths and process trajectories while performing real-time process monitoring. SwRI works closely with the ROS-I project to maintain its software repository and expand open-source automation solutions.

The solution includes custom machine vision algorithms that enable robots to apply various media with varying pressure based on the amount of surface work needed. Feature-based processing is also enabled through additions that leverage semantic segmentation approaches to apply the right tool to the right feature, cutting versus sanding for instance.

This project demonstrates the advanced features of ROS 2 while providing an initial framework for additional application build-out. It is also an open-source example for teaching and training those interested in developing advanced solutions that leverage ROS.

At Automate, SwRI will also share a new industrial reconstruction framework that creates high-fidelity mesh maps of objects. An onboard camera overlays the map to create a colorized mesh to facilitate advanced processing. The combination of 2D, 3D and color classification drives more intelligent processing. This new capability will be made available via the ROS-Industrial open-source program.

Continue Reading

News

Both gun owners and non-gun owners trust kids’ doctors in gun safety talks

Published

on

gun safety talks

New research shows that both gun-owning and non-gun-owning parents are open to discussions about gun locks and other firearm safety measures, especially when the conversation is with their child’s pediatrician. The study, led by researchers from the Perelman School of Medicine at the University of Pennsylvania, shows a possible avenue for reducing the number of firearm injuries and deaths suffered by children in the United States. The study was published in the Journal of Applied Research on Children.

“Parents appreciated a collaborative approach to decision-making and the emphasis on child safety,” said the study’s lead author, Katelin Hoskins, PhD, a postdoctoral researcher in the Penn Center for Mental Health. “Our findings add to a growing evidence base that a nonjudgmental, empathetic, and collaborative approach to firearm storage counseling enhances acceptability and potential effectiveness for behavior change.”

Hoskins and her colleagues, including the study’s senior author, Rinad Beidas, PhD, director of Penn Medicine’s Nudge Unit, founding director of the Penn Implementation Science Center, and a professor of Psychiatry and Medical Ethics and Health Policy, examined the reception of a firearm safety program called Suicide and Accident prevention through Family Education (S.A.F.E.) Firearm. S.A.F.E. Firearm involves a discussion between a child’s parent and a pediatrician, and focuses on secure storage of guns to keep them out of the hands of kids. A free cable lock is also offered through the program.

For the study, almost 100 parents watched a short video of a pediatrician delivering S.A.F.E. Firearm with a parent during a child’s doctor’s appointment. After the video, the parents who observed it filled out a survey. This occurred during the summer of 2020.

Researchers found that, overall, parents were very receptive to a pediatrician discussing firearm safety. On a five-point scale used in studies to measure “acceptability,” the pediatrician-delivered program scored a 4.35 average, with no significant difference between those who owned firearms and those who did not. More than 80 percent of the study’s participants said they would recommend that a friend receive the S.A.F.E. Firearm program from their child’s pediatrician. A slightly smaller percentage, 75, said they trusted their pediatricians’ advice on gun safety.

“Pediatric clinicians’ expertise in child health, child development, and treatment of firearm injuries enhances their credibility as firearm safety messengers,” Hoskins said. “Despite the politically sensitive topic of firearms, implementation of evidence-based interventions in pediatric primary care has great potential for reducing injuries and saving lives. An area for further inquiry is how length of relationship – how long a family has been connected to the same clinician – impacts trust and subsequent uptake of secure storage recommendations.”

The number of parents who owned firearms and participated in the survey was divided nearly evenly, with 46 percent of participants saying they had at least one. Among them, only about one in three said every one of their firearms was locked, unloaded, with ammunition stored elsewhere. But 64 percent of those parents indicated that they would change the way their firearms are stored after receiving the S.A.F.E. Firearm program.

Several recent incidents of gun violence make efforts like this all the more pertinent.

“The tragedies in Buffalo and Uvalde, plus the devastating loss of life due to firearm injuries right here in Philadelphia, underscore the importance of mobilizing across multiple sectors to prevent firearm deaths,” Hoskins said. “Recent data indicating that youth firearm suicide has reached its highest rate in more than 20 years adds additional urgency. The ASPIRE trial, which tests the most effective way to implement S.A.F.E. Firearm as a universal suicide prevention strategy, is currently underway. We are eager to learn from this work and identify best approaches for national implementation of firearm safety promotion.”

This study was funded by the National Institutes of Health (R24 HD087149).

 

 

Continue Reading

Trending