Items left behind in patients after surgery can have an enormous personal cost when organs and tissues are damaged. Surgical sponges are among the worst offenders – difficult to see in post-surgical X-rays and yet capable of causing holes when the intestines grow around them, for example. These rare cases, estimated around one in 3,000 surgeries that carry a risk, add up to around $1.5 billion in costs per year.
The current method of accounting for surgical tools involves counting them before and after surgery and performing an X-ray if there’s a mismatch. Without the metal bands inside them, the gauze sponges wouldn’t appear at all, but they are still difficult to see. A new, unmistakeable tag could change that – and its signature is so clear that computers can also detect it.
The tag, which is about the same size and shape as an acetaminophen tablet, contains four metal spheres, arranged at the points of a tetrahedron. This simple shape can be recognized by the computer no matter how it is turned. With human radiologists having a first look at the X-rays and then comparing their findings with a computer, over 98 percent of the tags can be seen. In contrast, as many as half of surgical sponges are missed in X-rays today.
The research team has formed the company Kalyspo, and they are building partnerships with surgical sponge manufacturers and hospitals in an effort to make the tag and software a standard part of surgical procedures, keeping patients safer.
Nikolaos Chronis, an associate professor of mechanical engineering at U-M, led the development of the tag. Theodore Marentis, then a radiology resident at U-M, identified the need for such a tag and worked with Chronis to develop and test it. Lubomir Hadjiyski, a professor of radiology at U-M, led the development of the software that locates the tags.
Chronis is also an associate professor of biomedical engineering and macromolecular science and engineering. Marentis is now a radiologist at the Mercy Medical Center in Mt. Shasta, CA.
In a study that could provide a roadmap for combatting the rising threat of drug-resistant pathogens, researchers have discovered the specific mechanism the body’s T-Cells use to kill bacteria.
University of Michigan researchers, in collaboration with colleagues at Harvard University, have discovered a key difference between the way immune cells attack bacteria and the way antibiotics do. Where drugs typically attack a single process within bacteria, T-Cells attack a host of processes at the same time.
On Thursday, the journal Cell published findings from a team headed by U-M’s Sriram Chandrasekaran and Harvard’s Judy Lieberman. It’s a study with potential implications for drug-resistant pathogens—a problem projected to kill as many as 10 million people annually across the globe by the year 2050.
“We have a huge crisis of antibiotic resistance right now in that most drugs that treat diseases like tuberculosis or listeria, or pathogens like E.coli, are not effective,” said Chandrasekaran, an assistant professor of biomedical engineering. “So there is a huge need for figuring out how the immune system does its work. We hope to design a drug that goes after bacteria in a similar way.”
We’ve reached a point where we take what antibiotics can do for granted, and we can’t do that anymore.Sriram Chandrasekaran
Killer T-Cells, formally known as cytotoxic lymphocytes, attack infected cells by producing the enzyme granzyme B. How this enzyme triggers death in bacteria has not been well understood, Chandrasekaran said.
Proteomics – a technique that measures protein levels in a cell—and computer modeling, allowed researchers to see granzyme B’s multi-pronged attack targeting multiple processes.
Chandrasekaran and his team monitored how T-Cells deal with three different threats: E. coli, listeria and tuberculosis.
“When exposed to granzyme B, the bacteria were unable to develop resistance to the multi-pronged attack, even after exposure over multiple generations,” Chandrasekaran said. “This enzyme breaks down multiple proteins that are essential for the bacteria to survive.
“It’s essentially killing several birds with one stone.”
The possible applications of the new findings on T-Cells run the gamut from the creation of new medications to the re-purposing of previously-approved drugs in combination to fight infections by mimicking granzyme B.
Chandrasekaran’s team is now looking at how bacteria hide to avoid T-Cell attacks.
And the need for a new approach in some form is dire. World Health Organization officials describe antibiotic resistance as “one of the biggest threats to global health, food security and development today.”
Each year, an estimated 700,000 deaths are linked to antibiotic-resistant bacteria, according to the World Health Organization. Projections show that number skyrocketing to 10 million by 2050.
England’s top health official, Sally Davies, recently said the lost effectiveness of antibiotics would mean “the end of modern medicine.”
“We really are facing—if we don’t take action now—a dreadful post-antibiotic apocalypse,” she was quoted saying earlier this month. “I don’t want to say to my children that I didn’t do my best to protect them and their children.”
Of particular concern is the fact that there are few new antibiotics in the pipeline. The heyday of new antibiotics occurred the 1940s through the 1960s, with releases eventually grinding almost to a halt by the end of the twentieth century.
“We’ve reached a point where we take what antibiotics can do for granted, and we can’t do that anymore,” Chandrasekaran said. “We’re taking inspiration from the human immune system, which has been fighting infections for thousands of years.”
The paper is titled, “Granzyme B disrupts central metabolism and protein synthesis in bacteria to promote an immune cell death program.” The research is funded by the National Institutes of Health, Harvard University and the University of Michigan.
by James Lynch, Research News & Feature Writer, Michigan Engineering
The University of Michigan is partnering on an ambitious $20 million project to grow new heart tissue for cardiac patients. The new research center has been awarded to Boston University (BU), with strong partnership from U-M and Florida International University (FIU).
“A heart attack creates scar tissue, and the heart never returns to full function. But for every person, we could create a living patch that a surgeon could stitch in,” said Stephen Forrest, who leads the nanotechnology aspect of the project and is U-M’s Peter A. Franken Distinguished University Professor of Engineering. “It’s very audacious.”
The project is a National Science Foundation Engineering Research Center. These 5-year grants are typically renewed for another 5 years, so the researchers are looking at a 10-year timeline to go from the current state of tissue engineering to working, implantable heart tissue.
A heart attack creates scar tissue, but we could create a living patch that a surgeon could stitch in.Steve Forrest
“Heart disease is one of the biggest problems we face,” said David Bishop, director of the new center and a BU professor of electrical and computer engineering and physics. “This grant gives us the opportunity to define a societal problem, and then create the industry to solve it.”
The living patches the researchers are developing would consist of heart muscle cells, blood vessels to carry nutrients in and waste out, and optical circuitry to make the heart muscle cells beat in synchrony. Already, researchers in the lab have been developing ways to structure cells in scaffolds that mimic particular organs and grow blood vessels into artificial tissues. But typically, working implants have been static, biodegradable materials such as artificial windpipes that the body gradually replaces with tissue. Working tissue, like heart muscle, would need to be responsive as soon as it was implanted.
Engineering Research Center grants are extremely competitive, with only four of more than 200 applicants receiving an award in 2017. These centers are designed to work directly with industry to translate breakthroughs along the way out of the lab and into healthcare. Just producing a more true-to-life “heart on a chip” could aid the pharmaceutical industry in developing better treatments for problems such as arrhythmia.
In order to produce the heart tissue, the team intends to start with an artificial scaffold that mimics the 3D structure of heart tissue. Joerg Lahann, a U-M professor of chemical engineering, will work with the team building the flexible polymer scaffold, as well as on the attachment and monitoring of cells within that framework.
“Michigan is pleased to lend expertise to the development of implantable heart tissue, which could improve and extend so many lives,” said Alec D. Gallimore, the Robert J. Vlasic Dean of Engineering. “Our faculty members are leaders in nanotechnology and in developing materials that support and interact with living cells and tissues, two areas that are critical to the project’s success.”
The 3D scaffold will initially be peppered with nanometer-sized gold patches that act as attachment points for protein fragments, called peptides, which will then serve as anchors for the cells. They will be printed onto the gold patches using a technique developed by Forrest and Max Shtein, a U-M associate professor of materials science and engineering. This method, called organic vapor jet printing, was initially invented for mass-producing electronic devices.
“The adaptation of this technology to biological systems represents a radically new step,” said Forrest. U-M will receive $2.8 million for these contributions.
Christopher Chen, the center’s director of cellular engineering and a BU professor of biomedical engineering, will lead the effort to grow heart muscle cells on the scaffold and infuse the tissue with blood vessels. Meanwhile, Alice White, director of nanomechanics and chair of the BU mechanical engineering department will work closely with Arvind Agarwal, an FIU professor of mechanical and materials engineering, to produce an artificial nervous system that uses light to synchronize the heartbeat in the tissue.
“It’s humbling to have the opportunity to work on something that could really be a game changer,” says Bishop. “If we succeed, we’ll save a lot of lives and add meaningful years for many people.”
In addition to the technical thrusts led by Forrest, Chen and White, Thomas Bifano, a professor of mechanical engineering and director of BU’s Photonics Center, will direct imaging.
Along with the core partners, Harvard Medical School, Columbia University, the Wyss Institute at Harvard, Argonne National Laboratory, the École Polytechnique Fédérale de Lausanne in Switzerland, and the Centro Atómico in Argentina will offer expertise in bioengineering, nanotechnology, and other areas.
Forrest is also the Paul G. Goebel Professor of Engineering, and a professor of electrical engineering and computer science, material science and engineering, and physics. Lahann is also a professor of material science and engineering, biomedical engineering, and macromolecular science and engineering. Shtein is also an associate professor of chemical engineering, macromolecular science and engineering, and art and design. Gallimore is also the Richard F. and Eleanor A. Towner Professor, an Arthur F. Thurnau Professor, and a professor of aerospace engineering.
by Kate McAlpine, Senior Writer & Assistant News Editor, Michigan Engineering