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URMC Awarded Nearly $6 Million to Study Deadly Bone Infections

Monday, November 6, 2017

Bone infection, while relatively rare, can be debilitating and potentially fatal. In recent years, researchers in the Center for Musculoskeletal Research at the University of Rochester Medical Center have made several discoveries that position them to advance new treatments and possible cures for bone infections. Now, a nearly $6 million, 5 year award from the National Institute of Arthritis and Musculoskeletal and Skin Disease at the National Institutes of Health, will allow the group to create a new multidisciplinary research program devoted to studying bone infections.

The CMSR has been among the top five NIH-funded orthopaedic research centers in the nation for over ten years, and Edward Schwarz, Ph.D., Burton Professor of Orthopaedics and director of the CMSR, has been the top NIH-funded orthopaedic researcher in the nation three years running. This new grant, awarded to Schwarz and throng of researchers from across the University of Rochester and beyond, brings the center’s total forecasted earnings for 2017 to $28 million.

Of the millions of Americans who have joint replacement surgeries each year, less than five percent come away with an infection. But this minority of patients must endure a long and difficult road to recovery, if they recover at all. The vast majority of these infections are caused by a bacteria called Staphylococcus aureus, including the dreaded methicillin-resistant strain (MRSA), which causes sepsis and death in 13 percent of infected patients.

Patients who survive these infections face multiple surgeries to remove infected tissue, months of strong antibiotic treatments, and a high likelihood of re-infection. For a long time, researchers have been working to understand how this bacteria evades treatment and Schwarz believes he has figured out.

Together with Karen Bentley, director of the Electron Microscopy Core at URMC, Schwarz showed that the bacteria can crawl deep into tiny channels in bones, possibly taking shelter there and later emerging to re-establish an infection. Though S. aureus was originally thought to be incapable of movement, Bentley and Schwarz, in collaboration with James McGrath, Ph.D., professor of Biomedical Engineering at URMC, and his spin-off company, SiMPore Inc., showed that this bacteria can migrate through tiny pores in membranes in the lab.

This new grant will allow Schwarz and Hani A. Awad, Ph.D., professor of Biomedical Engineering and Orthopaedics in the CMSR, to investigate exactly how S. aureus gets into bone and develop new treatments that target those mechanisms. Microbiologists Steven Gill, Ph.D., and Paul Dunman, Ph.D., in the Department of Microbiology and Immunology, will help the team develop new antibiotics to inhibit bone infection, which will be 3D printed into spacers that replace infected joint implants. Delivering the antibiotic at the site of infection may save patients’ limbs and lives.

Schwarz has also been working to understand what makes certain patients more susceptible to S. aureus infections than others, including why some patients recover relatively easily, while others die.

“Death following surgical site infection is not random,” said Schwarz. “By studying patient immune responses to this bacteria, we might be able to predict who will be fine and who will need extra medical attention.”

S. aureus can also become resistant to antibiotics, making it extremely deadly and difficult to eradicate. Better understanding patients’ immune reactions to the bacteria may provide new approaches to defeating it.

In an international study of more than 300 patients with infected total joint replacements, Schwarz and his team including John Daiss, Ph.D., and Chao Xie, M.D., in the CMSR, found that patients fared well if their immune systems attacked a certain S. aureus protein, and poorly if they attacked another. Patients who produced antibodies attacking autolysin, a protein important for cell division, were protected. Those who produced antibodies against a family of iron sensing determinant (Isd) proteins, which help S. aureus sap nutrients from its host, were more likely to experience sepsis and even die.

It is unclear why antibodies that attack Isd proteins are bad for patients, and Schwarz is determined to use this new funding to figure it out. He will also analyze the full complement of antibodies produced by patients infected with several types of staph bacteria to see if there are more good- and bad-cop antibodies that could help inform new treatments.

The Clinical Research Core of this program will be run by Stephen L. Kates, M.D., at Virginia Commonwealth University.

Read More: URMC Awarded Nearly $6 Million to Study Deadly Bone Infections

Gene and Stem Cell Therapies May Help Heal Fractures

Monday, June 12, 2017

Hani Awad, Ph.D.,​URMC researchers partnered with Cedars-Sinai colleagues on a study that tested a new method for repairing severe fractures in laboratory animals. The new technique combines ultrasound, stem cell, and gene therapies to cue bone to regenerate itself. Researchers believe the technique may someday replace bone grafting as a way to mend severe fractures.

On average, about 100,000 people in the U.S. experience severe fractures that fail to heal each year. The current standard of care for these injuries often involve long hospital stays, repeated surgeries, and still result in long-term disability. 

While bones are usually able to repair themselves in the case of small cracks and fractures, severe breaks and fractures leave too big a gap for bones to fill on their own. In these cases, missing bone may be replaced by bone from another place in patient’s body, which is painful and may cause infection at the donor site, or by a piece of bone from a cadaver, does not always integrate well with the patient’s bone because it is dead tissue.

The new fracture-healing method published in the journal Science Translational Medicine, helped bones regenerate across large gaps in leg fractures of laboratory animals. Hani Awad, Ph.D., professor of Biomedical Engineering and Orthopaedics at the University of Rochester Medical Center, tested the healed fractures in Center for Musculoskeletal Research’s state-of-the-art Biomechanics Lab with the help of Jayne Gavrity, a biomechanical and imaging engineer in the CMSR. According to Awad, the newly formed bone was as strong as the patient’s own bone grafts, suggesting the new procedure could replace the painful grafting procedure.

To heal the fractures, the team filled the fracture gaps with a scaffold of collagen, a structural protein the body normally uses to make bone. Over two weeks, stem cells were recruited to the scaffold in the fracture site. Then the team delivered a gene to the stem cells that would turn them into bone-creating cells. The gene was delivered with the aid of microbubbles that create tiny holes in the stem cell membrane and enable entry of the gene into the cells when they are hit with pulses of ultrasound.

This technique, which improves upon other investigational therapies that are costly, painful, and increase risk of infection and tissue damage near the fracture site, was able to completely heal leg fractures in the laboratory animals in just eight weeks.

Co-senior authors, Dan Gazit, Ph.D., D.M.D., co-director of the Skeletal Regeneration and Stem Cell Therapy Program in the Department of Surgery and the Cedars-Sinai Board of Governors Regenerative Medicine Institute, and Gadi Pelled, Ph.D., D.M.D., assistant professor of surgery at Cedars-Sinai, hope this technique will be useful in humans, but more studies are needed to determine this.

The study was featured in Science Magazine, a publication of the American Association for the Advancement of Science. You can find that article here.  

To read the full study, click here.

Susanne Pritchard Pallo | 6/12/2017

Bones made to order: UR Medical Center attempting to use 3-D printing, stem cells to regenerate bone tissue

Monday, February 27, 2017

Birbeck

Hani Awad (left) and Edward Schwarz

This news story appeared in the Democrat & Chronicle on February 27, 2017. It features University of Rochester biomedical engineering professors Hani Awad and Edward Schwarz, who are leading the way in using 3-D printers and stem cells to create bone replacements for patients. The online version can be found here.

Imagine getting a made-to-order bone implanted in your body that's composed of your own cells.

Scientists at the University of Rochester Medical Center have been developing a procedure to use 3-D printing and stem cells from the patient to create bones made of regenerated tissue.

This multi-step procedure still has a ways to go before it is tested on humans and can become part of the services provided by URMC's Center for Musculoskeletal Research. But it's the latest example of how 3-D printing, which is increasingly finding its place in manufacturing, is leaving its mark in medicine.

“It is changing the way we do a lot of things,” said Hani Awad, who is associate director of the center and professor of biomedical engineering with a specialty in tissue engineering.

Biomedical research, as it is being done in this initiative, is an important component of the medical center's identity.

"Part of our mission is that we want to do research that is impactful," said Stephen Dewhurst, vice dean for research at the medical center.

Read More: Bones made to order: UR Medical Center attempting to use 3-D printing, stem cells to regenerate bone tissue