University or Institution

University of Pennsylvania

Area of Research:

What innovative approaches to tackle medical biofilms are needed? How can we make other stakeholders (e.g. medical care providers, engineers, veterinarians, regulatory bodies and other professionals) aware that biofilms are important?

Primary Mentor:

Thomas P Schaer, VMD Director Institute for Medical Translation at Penn Vet School of Veterinary Medicine New Bolton Center Kennett Square, PA 19348

Mentor Team:

Shelley C Rankin, PhD Professor of Microbiology Chief of Clinical Microbiology Ryan Veterinary Hospital University of Pennsylvania School of Veterinary Medicine

Javad Parvizi MD, FRCS James Edwards Professor of Orthopedic Surgery, Sidney Kimmel Medical College Rothman Institute at Thomas Jefferson University Hospital Sheridan Building, Suite 1000 125 South 9th Street Philadelphia, PA 19107

Noreen J Hickok, PhD Professor Department of Orthopaedic Surgery Department of Biochemistry & Molecular Pharmacology Thomas Jefferson University Philadelphia, PA 19107

Description of Potential Research Project(s):

Despite stringent sterile technique and aggressive antibiotic prophylaxis, otherwise safe and effective surgery can become a patient’s worst nightmare. Once infection is established, at rates of 1.5% for knee revisions, 0.7 to 11.9%, for spinal infections, depending on the complexity of the procedure, and up to 27% for open fractures, eradication is extremely difficult. To stimulate the immune response to combat the infection, we propose a novel therapy using cold plasma and cold plasma activated liquid (PAL). These novel modalities generate a complex mixture of reactive species which can be tailored for high microbicidal activity coupled with immune cell stimulatory properties. Our preliminary data and multiple published reports, indicate that cold plasma and PAL, stimulate immune activation in mouse cancer models, promote tissue healing and eradicate even antibiotic resistant pathogens. Based on these studies, we hypothesize that treatment of infected tissues and hardware with cold plasma will activate immune surveillance, eradicate established bacterial biofilms, to foster tissue repair, thereby generating a "personalized" response to orthopaedic infection. There are 3 NIH funded Specific Aims:

Specific Aim 1. Investigate MRSA infection control mechanisms associated with direct cold plasma treatment.

Specific Aim 2. Investigate the composition, mechanisms of action, and efficacy of Plasma Activated Liquid (PAL) alone and in combination with direct cold plasma treatment in a rat model of MRSA infected fracture fixation.

Specific Aim 3. Investigate the efficacy of combined cold plasma and PAL treatments (SA1 and SA2) in a clinically relevant sheep MRSA infected osteotomy model.

Additional Training Opportunities:

Dr. Schaer is the director of the Institute for Medical Translation at Penn Vet and a Member of the Penn Health-Tech Executive Committee. His research program has been continuously funded since 2005 and functions as an ecosystem for multidisciplinary collaboration and the mentoring of graduate and undergraduate students in the translational sciences. This ecosystem functions as a conduit from basic research to applied, hypothesis- driven investigations exploring efficacy and mechanistic processes continuously informed and challenged by clinical practice. A particular strength of this program is the close collaboration between clinician-scientists (Parvizi, Hickok) and a multidisciplinary team of investigators which informs research that has strong clinical relevance with the potential of moving into clinical applications. This has led to the global launch of 12 new technologies. The program is committed to weekly lab meetings (Schaer) guiding the fellows toward completion of their studies but also developing their own independent research studies. Monthly meetings with project-specific collaborators will be scheduled in person or via remote (Schaer, Rankin, Parvizi, Hickok). The fellow will be expected to complete the T32 run “Training in the Responsible Conduct of Research and Scientific Rigor and Reproducibility” program. The T32 training programs also offer “Individual Development Plans”, “Career Development”, and “Professional Development”. Relevant seminars include those scheduled monthly by the Penn Center for Musculoskeletal Disease 1 , Institute for Regenerative Medicine 2 , and McKay Orthopedic Research Laboratory, the many annual Research Symposia on Penn Campus. Recent development of programmatic support of entrepreneurship at Penn has unleashed enormous enthusiasm in the translational space (i.e. Wharton Y-Prize Competition, Rothenberg Catalyzer, Penn Center for Health, Devices and Technologies).

1 Schaer is member of the Penn Center for Musculoskeletal Disease

2 Schaer is member of the Institute for Regenerative Medicine

Contact Information for Interested Potential Trainees:

Thomas P Schaer, VMD Director Institute for Medical Translation at Penn Vet School of Veterinary Medicine New Bolton Center Kennett Square, PA 19348

[email protected]