ABSTRACT This proposal addresses NIOSH sector of Healthcare and Social Assistance (HCSA) program (NAICS 62) and significant components of the Immune, Infectious and Dermal Disease Prevention (IID) cross sector. Over 21 million people are covered by the HCSA program in the United States and occupational IID diseases are of the most common illnesses affecting their safety and health. Personal protective equipment (PPE) as major intervention means is critical for healthcare workers? (HCWs) health and safety. However, ineffective PPE can place HCWs and patients at risk of transmission of infectious agents, not only through direct contact with blood and body fluids, but also via microbial penetration through barrier fabrics, and aerosol and droplet transmission. Current PPE is not ideally suited to the needs of HCWs due to limitations in protection and comfort, such as self-contamination during doffing, poor fit and inward leakage risks offered by respirators, insufficient capture of airborne pathogens, difficulties in communication through materials, potential fluid penetration, and poorly executed fit and sizing. Limitations of current PPE have resulted in infections and mortalities of HCWs in fighting against recent outbreaks such as Ebola, SARS, and COVID-19. The overall goal of this project is to develop improved PPE for HCWs with an emphasis on self-decontaminating function. In this project, we will develop new textile materials with self- decontaminating property. Then, we will apply both the existing material and those materials developed in this project to isolation gown and respirator. A novel design approach will be applied to create a new, seamless, self-decontaminating PPE system with superior comfort, fit, and functionality compared with those of any currently available PPE. The evidence- based design process will incorporate three-dimensional (3D) body scanning and kinematic motion analysis to achieve greatly improved wearability and functionality. We will use the recently developed and validated Faceseal concept to develop a filtering facepiece respirator (FFR) made of biocidal material that will have a close-to-perfect fit. A Simulated Workplace Protection Factor (SWPF) will be determined for the new respirator. The overall PPE performance design will be evaluated using instrumented manikins, specifically designed human trials, and performance testing. The data obtained from these evaluations will be applied to further improve the newly-developed PPE components. The multidisciplinary team is well prepared to carry out the proposed work with established knowledge and successful track records in fiber/polymer science, textiles, PPE design and performance evaluation, respirator design, aerosol research, and exercise physiology and kinesiology. The state-of-the-art facilities and equipment across the collaborating institutes are ideally suited to fulfill the research aims. Clinicians and epidemiologists will serve as consultants on the project, offering insights and firsthand experiences of PPE implementation and utilization. This proposed project is significant since it embraces NIOSH r2p initiative by fundamentally directing novel PPE material and end products development and providing the technical basis in performance evaluation methods. The completion of the work will raise the horizon of PPE engineering in reducing occupational IID diseases and targeting the intermediate goal of addressing infectious disease transmission in the HCSA sector. The end outcomes of this proposed project will benefit millions of HCWs and save billions of healthcare costs.