More than 2 million Americans are hospitalized each year with bone fractures, and many more undergo outpatient procedures for fracture reduction and fixation. Some injuries can be treated with closed reduction and splinting or casting to immobilize the bone during healing. However, at some sites, more than half of fractures require open reduction and internal fixation. Despite advances in implant materials, implant-associated infections remain a challenge. Depending on the location of the fracture, characteristics of the injury (e.g., open vs. closed fracture), and characteristics of the patient (e.g., presence of diabetes or other comorbidities), between 1% and 30% of fixation sites are compromised by device-associated infections. For example, lower extremity fractures requiring internal fixation are associated with high infection rates that impede bone healing, increase the risk of long-term disability, and increase the cost and complexity of patient care. Further advances in fixation device materials are needed to reduce the incidence of device-associated infections and improve patient outcomes. In this Phase I STTR, SINTX Technologies seeks to demonstrate proof-of-concept for a novel antimicrobial material that could be used to produce a broad range of internal fixation devices for fracture repair. Trauma plates are the most widely used internal fixation devices in trauma applications. Plates are typically crafted from metal, molded carbon fiber reinforced (CFR) polyetheretherketone(PEEK) composites, or CFR-polyetherketoneketone (CFR-PEKK). Unfortunately, devices made from all of these materials are prone to infection. SINTX pioneered the use of silicon nitride (Si3N4) implants that have inherent antimicrobial activity and have achieved an excellent anti-infective profile in clinical use (i.e., only 0.006% of implants have been associated with infection). Although Si3N4 has excellent antimicrobial properties, it is susceptible to brittle fracture and therefore not suitable for stabilizing fractures. In this Phase I STTR, SINTX and its collaborators propose to use a proprietary process to embed microscopic Si3N4 powder into the surface of CFR-PEKK and evaluate this novel material's performance as an antimicrobial material for fixation devices. Trauma plates will serve as a prototype for proof-of-concept, with the goals of a) advancing a Si3N4-CFR-PEKKtrauma plate for further development and commercialization and b) demonstrating the potential for the material to be used in other fixation devices that must withstand in vivo loading, facilitate imaging, and resist infection. Aim 1. Design an α-Si3N4 -CFR-PEKK trauma plate that meets or exceeds requirements for static and fatigue bending strength. Aim 1 Milestone: Design and develop a Si3N4-coated CFR- PEKK trauma plate that preserves at least 90% of static and fatigue bending strength of uncoated trauma plates in accordance with ASTM F382, D7264, D790-10. Aim 2. Characterize antibacterial activity and biocompatibility as a function of α-Si3N4 percentage. Aim 2 Milestone: A > 2 log reduction in bacterial colonization while retaining osteoblastic proliferation/maturation.
Public Health Relevance Statement: Project narrative: Implantable devices used to repair bones following trauma can introduce or promote bacterial infection that delays healing and can cause other complications. This project is designed to advance the development of a new composite material for implantable bone repair devices by embedding antibacterial alpha silicon nitride into the surface of a commonly used carbon fiber reinforced plastic. Surgical use of this new material is expected to reduce the risk of infection in bone repair and prevent the device from becoming a source or reservoir of infection.
Project Terms: Performance, ductile, novel, Devices, Property, preventing, prevent, pre-clinical testing, Preclinical Testing, in vivo, in vivo Model, research clinical testing, Clinical Evaluation, Clinical Testing, clinical test, Patient-Focused Outcomes, Patient outcome, Patient-Centered Outcomes, Small Business Technology Transfer Research, STTR, Characteristics, Process, sample fixation, Fixation, Development, developmental, Image, imaging, pre-clinical, preclinical, cost, healing, Advanced Development, design, designing, Trauma, antimicrobial, anti-microbial, Implant, bone healing, bone wound healing, osseous wound healing, prototype, commercialization, Formulation, preservation, infection risk, implant associated infection, implant related infection, infection rate, rate of infection, osteoblast proliferation, Impaired healing, Healing abnormal, Healing delayed, bone fracture repair, Fracture Healing, bone fracture healing, fracture repair, bone repair, Animals, Anti-Infective Agents, Anti-Infective Drugs, Anti-Infectives, Anti-infective Preparation, AntiInfective Drugs, AntiInfectives, Antiinfective Agents, communicable disease control agent, Bacterial Infections, bacteria infection, bacterial disease, Biocompatible Materials, Biomaterials, biological material, Biomechanics, biomechanical, bone, Cells, Cell Body, comorbidity, co-morbid, co-morbidity, Diabetes Mellitus, diabetes, Escherichia coli, E coli, E. coli, Exhibits, Fatigue, Lack of Energy, Foundations, Fracture, bone fracture, Closed Fractures, Future, Patient Care, Patient Care Delivery, Goals, Human, Modern Man, Immobilization, orthopedic freezing, implantable device, biomedical implant, implant device, indwelling device, Incidence, Infection, Metals, NIH, National Institutes of Health, United States National Institutes of Health, Osteoblasts, Out-patients, Outpatients, Patients, Powders, Powder dose form, General Radiology, Radiology, Radiology Specialty, Reinforcement, Psychological reinforcement, Research, Risk, Splints, Splint Device, S aureus, S. aureus, Staph aureus, Staphylococcus aureus, Technology, Time, silicon nitride, Si3N4, Internal Fixators, Internal Fixation Devices, polyetheretherketone, carbon fiber, carbon felt, Injury, injuries, Lower Extremity Fracture, improved, Procedures, Site, Area, Surface, Clinical, Microscopic, Phase, disability, Antibacterial Agents, anti-bacterial, antibacterial, Anti-Bacterial Agents, Filamentous Fungi, Molds, implant material, Source, Location, Operative Procedures, Surgical, Surgical Interventions, Surgical Procedure, surgery, Operative Surgical Procedures, Prevent infection, Infection prevention, Surgeon, American, biocompatibility, biomaterial compatibility
