7. Project Summary/Abstract [Revised] For the past 60 years all hollow fiber dialyzers have had intraluminal blood flow. Novaflux outside-in filtration (OIF) creates a new design paradigm for hollow fiber dialyzers, changing dialyzer flow distribution so that blood flows on the outside of the fiber and dialysate flows in the intraluminal space. This development reduces the need for anticoagulation for acute or chronic dialytic therapies, including hemodialysis (HD) and provides increased filter life for continuous renal replacement therapies (CRRT). In vitro data using conventional dialyzers with OIF flow have found increased filter life to over 100 hours as compared to ~24 h with standard flow with statistically equivalent clearance. In OIF, thrombi have a minimal effect on the blood flow or filter pressure, diffusive clearance, or filtrate flux due to dynamic three-dimensional interconnected flow channels created in the inter fiber space. Novaflux research has developed prototype fibers that reverse the conventional dialyzer membrane structure to provide a thin tight smooth hemocompatible outer skin. The OI fiber will prevent damage to blood cells or formation of platelet aggregates. Novaflux OI filter housings optimize the blood inlet design using novel flow geometries, modeling and computation flow dynamics to provide steady blood velocity and uniform blood flow distribution. OIF dialyzers will be able to be produced by current dialyzer production equipment with relatively minor modifications. The value proposition of OI dialyzers is to reduce or eliminate the need for anticoagulation for chronic hemodialysis. This brings about key benefits including: 1) Lowering risk of heparin related complications such as bleeding and blood loss post treatment; 2) Providing a no-anticoagulation alternative for Heparin-Induced Thrombocytopenia; 3) Lowering the cost by $0.70 to $1.60 per treatment due to reduction in the use of heparin; 4) Reduction of microemboli which may pass from the extracorporeal circuit to the patient, causing ischemic lesions in organs such as the brain, which may contribute to dialysis dementia; and 5) Lower clotting potential facilitates development of wearable renal treatments. The OI filter can help acute dialytic renal treatments by providing no or reduced anticoagulation and longer filter life in CRRT, which translates into: 1) Lower cost and complexity for the healthcare provider; and 2) Reduced need for complex anticoagulation regimes, e.g., regional citrate anticoagulation. The Phase II will scale up the OIF membrane and housings to produce prototype OI dialyzers for in vitro and animal studies to characterize performance and hemocompatibility. These studies will quantify the potential of OI technology to eliminate or reduce anticoagulation for dialytic therapies and to provide clinical benefits and cost reductions compared to current acute and chronic therapies. The Specific Aims of this two year program are: Aim 1: Dev...