Fiber design and assessment for development of a novel biomimetic medical device

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Abstract. The Selective Cytopheretic Device (SCD) is an extracorporeal, blood contacting medical device targeted to treat patients with inflammatory disease indications. SCD therapy is similar to hemodialysis in that catheters and medical tubing are used to pass the patient’s blood through the device. The patient’s white blood cells (WBC), also called leukocytes (LE), come in contact with the hemocompatible fibers inside the SCD. These fibers are capable of immunomodulatory interactions with the patient’s over-active (or activated) WBC. The SCD has been safely used in 4 human clinical studies to date, 3 trials in adults and 1 trial in adolescent patients, with positive clinical outcomes for critically ill patients with acute kidney injury (AKI) and multiorgan dysfunction (MOD). Long term objective: Develop a proprietary formulation of medical grade fibers with an outer diameter (OD) ≤ 140 µm, for use in a second generation SCD (SCD2) with low blood fill volumes (BFV) to enable the treatment of pediatric patients and critically ill adult patients with blood volume removal re- strictions due to potential hemodynamic instability. Fibers within the current SCD (SCD1) are made of polysul- fone (PSu) and have an OD of 280 µm. These fibers are too large to be used in SCD2, causing the BFV to be too high, which is not safe for pediatric patients and critically ill patients. A safe BFV of <50 mL will be achieved for SCD2 using ~140 µm OD fibers. A new, boutique fiber manufacturing facility with ISO 13485 certification (Hollow Fiber Systems) will be utilized to manufacture medical grade fibers. Fibers will be tested in a series of studies to rapidly develop SCD2 for clinical translation to save severely ill patients' lives. In the previously completed Phase I project period, the way the SCD1 used in clinical trials works was characterized, called the mechanism of action (MoA). Main features of MoA that were elucidated include: LE adhesion to SCD fibers, with a specific adhesion of monocytes (MO) and neutrophils (NE). To advance propri- etary fiber development, an optimal range of hydrophilic agent to add to the PSu material during fiber produc- tion was established. In this Phase II proposal, proposed studies include: Aim 1. Characterize proprietary med- ical grade fibers produced by custom manufacture. Evaluate fibers in miniaturized prototype SCD2 utilizing in vitro blood circuit (IVBC) with human blood. Aim 2. Produce full-size pediatric-SCD2. Evaluate SCD2 design in IVBC studies with porcine blood to assess SCD-LE interactions and hemocompatibility. Aim 3. Evaluate SCD2 in a clinically relevant porcine model of severe sepsis (SS) associated-AKI. Aim 4. FDA regulatory biocompati- bility, sterilization and shelf-life testing of SCD2. Health Related Impact: Preclinical data generated from this proposal will be included in regulatory submissions to apply for IDE approval from the FDA to initiate clinical trials for the evaluation of SCD2 therapy in both acute and chronic disease indications, staring with orphan dis- eases: pediatric AKI, atypical hemolytic uremic syndrome (aHUS) and cardiorenal syndrome (CRS) patients with left ventricular assist device (LVAD) destination therapy (DT) that may benefit from SCD2 therapy.