Document text
Principal Investigator: Paula Bourke
Organization: THOMAS JEFFERSON UNIVERSITY
Fiscal Year: 2024
Award: $646,298
Funding agency: National Institute of Arthritis and Musculoskeletal and Skin Diseases
ABSTRACT
Orthopaedic infection is life-threatening and current treatments are only sparingly successful. Despite
aggressive peri-operative antibiotic treatments, 1.5% of knee revisions, 0.7 to 11.9%, of spinal infections
(depending on the complexity of the procedure) and up to 27% of open fractures become infected. Moreover,
the complexity of tissues interfacing with the biofilm-prone orthopaedic instrumentation complicates bacterial
eradication making current treatments prolonged and expensive. To address this serious issue, we propose to
combat the infection using cold plasma and cold plasma activated liquid (PAL). Our pilot data show that these
novel modalities can be tailored for high microbicidal activity coupled with immune stimulatory properties
without the risk of antibiotic resistance. Importantly, these modalities have not been used to combat bone
infections. To utilize this technology to address orthopaedic infection, a tri-partite consortium of international
research teams at the forefront of cold plasma technology from the US, the Republic of Ireland and Northern
Ireland have been assembled. This consortium unites expertise in plasma engineering, microbiology, material
science, chemistry, cell biology, and clinical medicine. There are three Specific Aims. (1) To determine the
effect of direct cold plasma treatment on MRSA biofilms and immune cell response; (2) To determine the
mechanisms of action, and efficacy of Plasma Activated Liquid (PAL) alone and in combination with direct cold
plasma treatment to eradicate infection; and (3) To resolve infection through combined cold plasma and PAL
treatments in a clinically relevant animal model of infected osteotomy. We will develop cold plasma and PAL
treatments that will directly disrupt biofilms and eradicate bacteria while stimulating the immune response. At
the end of this study, we will have developed a simple and effective non-antibiotic treatment protocol to cure
surgical site infection through combined immune activation and direct eradication of bacteria. Clinically, this
cold plasma+PAL treatment protocol can be seamlessly integrated with existing clinical protocols to enhance
and eventually replace our reliance on antibiotic therapies.
Terms: <Address><Animal Model><Animal Models and Related Studies><Anti-Bacterial Agents><Antibiotic Resistance><Antibiotic Therapy><Antibiotic Treatment><Antibody titer measurement><Antiseptics><Area><Bacteria><Bacterial Antigens><Biocide><Blood Plasma><Blood leukocyte><Body Tissues><Bone Infection><Cancers><Cell Body><Cells><Cellular biology><Chemistry><Chemotactic Cytokines><Clinical><Clinical Medical Sciences><Clinical Medicine><Clinical Protocols><Common Rat Strains><Compound Fractures><Coupled><Data><Dendritic cell activation><Detection><Effectiveness of Interventions><Eire><Engineering><Eukaryotic Cell><Fracture><Fracture Fixation><Homologous Chemotactic Cytokines><Immune><Immune Cell Activation><Immune Surveillance><Immune response><Immune system><Immunes><Immunologic Stimulation><Immunologic Surveillance><Immunologic Surveillances><Immunological Stimulation><Immunological Surveillance><Immunological Surveillances><Immunological response><Immunostimulation><Immunosurveillance><Impairment><Implant><Infection><Inflammatory><Intercrines><International><Investigators><Ireland><Irish Free State><Knee><Leukocytes><Leukocytes Reticuloendothelial System><Life><Liquid substance><Local Anti-Infective Agents><MRSA><Macrophage><Malignant Melanoma><Malignant Neoplasms><Malignant Tumor><Marrow leukocyte><Melanoma><Methicillin Resistant S. Aureus><Microbial Biofilms><Microbiology><Modality><Modeling><Mφ><Nature><Northern Ireland><Open Fractures><Organism><Orthopedic><Orthopedic Surgical Profession><Orthopedics><Osteomyelitis><Osteotomy><Ovine><Ovis><Penetration><Perioperative><Phagocytosis><Plasma><Plasma Serum><Procedures><Production><Property><Rat><Rats Mammals><Rattus><Reproducibility><Research><Research Personnel><Researchers><Resistance to antibiotics><Resistant to antibiotics><Reticuloendothelial System, Serum, Plasma><Risk><SIS cytokines><Sheep><Site><Skeletal Fixation><Spinal><Surgical Wound Infection><Technology><Testing><Tissues><Topical Anti-Infective Agents><Toxic effect><Toxicities><Treatment Protocols><Treatment Regimen><Treatment Schedule><White Blood Cells><White Cell><anti-bacterial><anti-microbial><antibiotic drug resistance><antibiotic resistant><antibiotic resistant pathogen><antibody titering><antimicrobial><bacterial disease treatment><bacterial infectious disease treatment><biofilm><bone><bone fracture><cell biology><chemoattractant cytokine><chemokine><clinical relevance><clinically relevant><combat><compare intervention><comparison intervention><cytokine><drug resistant pathogen><fluid><healing><host response><immune activation><immune system response><immunoresponse><instrumentation><liquid><living system><malignancy><materials science><methicillin resistance Staphylococcus aureus><methicillin resistant Staphylococcus aureus><methicillin resistant strains of Staphylococcus aureus><microbicidal><microbicide><model of animal><neoplasm/cancer><new approaches><novel><novel approaches><novel strategies><novel strategy><programs><recruit><response><standard of care><surgical site infection><white blood cell><white blood corpuscle>