Project Summary Abstract The Centers for Disease Control and Prevention (CDC) reports that preventing ventilator associated pneumonia (VAP), as opposed to treating the acquired infection, is a critical and unmet need. To respond to this need, Iasis Molecular Sciences will leverage strong preliminary data obtained for proprietary antimicrobial compositions (composites). Excellent antimicrobial performance and material cytocompatibility could be beneficial in the creation of a next generation endotracheal tube that could substantively reduce VAP. SupraGuardTM ETT is an advanced device wholly constructed from an antimicrobial composite designed to kill microorganisms known to cause VAP. The compositions are effective against organisms intraluminally or those located in subglottic fluids that have pooled above the cuff while maintaining excellent mechanical characteristics. The proposed research will address ETT composite formulation, composite processing, microbial inactivation, composite biocompatibility and stability, and ETT cuff viability. The major specific aims of the proposed research include: 1.) Finalizing SupraGuardTM Next Generation Antimicrobial Endotracheal Tube & Cuff Materials Development, 2.) Measure the Antibacterial & Antifungal Effectiveness of the SupraGuardTM Composites. 3.) Evaluate the In Vitro & In Vivo Biocompatibility of SupraGuardTM Composites. There is significant commercial potential for our product, as the antimicrobial-coated ETT component of the ETT market was valued at $1.84B in 2018 and whereby the majority of antimicrobial ETTs are silver-coated ETTs. However, there are no products today that possess effective antimicrobial ETT cuffs that can effectively kill pathogens.