PROJECT SUMMARY Catheter-related bloodstream infection (CRBSI) is a leading cause of healthcare-acquired infections (HAIs) and is associated with high mortality (12–25%) and cost ($9 billion in the US). Catheter-related thrombosis (CRT) is another common complication with central venous catheters (CVCs) that contributes to 41% of premature device removal before treatment is over. Although various coatings, including those with anti-thrombogenic or antimicrobial agents have been applied, the safety and clinical efficacy of these coatings to reduce the rates of CRBSI and/or CRT remains unsatisfactory, especially for extended implantation. LiquiGlide is investigating a new coating solution to overcome the limitations. Liquid-impregnated surface (LIS) provides a non-adherent, self-healing, and replenishable surface that other coatings cannot achieve. Formulating a LIS coating with parenteral nutrient ingredients that have been approved by FDA for intravenous administration, confirming their safety, we have developed a coated surface that significantly reduces thrombus formation and bacterial colonization. When the coating is applied on a vascular catheter, the parenteral nutrients can be replenished through the catheter lumen to increase the duration of efficacy, which is especially beneficial as occlusion and long-term CRBSI occur predominantly through the intralumenal pathway. In preliminary studies, we demonstrated the safety and patency of coated catheters in a swine model during an implantation with three replenishments. The objective of this proposal is to develop the LIS coating on a peripherally inserted central catheter (PICC) to eliminate occlusion and reduce infection in long-term implantation with a side-by-side comparison in a same animal. To achieve the objective, we will first apply the coating on a PICC, meeting the safety and durability requirements as a vascular implant. Then, the LIS-coated PICC will be evaluated in vitro to assess its ability to prevent thrombosis formation (>95% reduction) and achieve 100% elimination of occlusion (Aim 1) under simulated external flow and infusate injections. We will further demonstrate that the coated device has a broad spectrum anti-microbial resistance (Aim 2), targeting reducing both bacterial colonization and biofilm formation with >99% reduction with three typical microorganisms that commonly cause CRBSI. To evaluate the safety and anti-occlusion/anti-infection efficacy in vivo, we will perform a seven-animal study with a swine model, monitoring catheter patency and microorganism colonization on the devices during implantation and assessing explants for thrombus formation and microbial cultures/identification (Aim 3). The proposed phase I study will address challenges related to replenishable LIS-coated PICCs, achieving full occlusion elimination and significant CRBSI reduction. Upon achievement of the phase I milestones, the coated PICC will be ready for the next level of product developme...