An arteriovenous mock circulatory loop and accompanying bond graph model for in vitro study of peripheral intravascular bioartificial organs.

BACKGROUND: Silicon nanopore membrane-based implantable bioartificial organs are dependent on arteriovenous implantation of a mechanically robust and biocompatible hemofilter. The hemofilter acts as a low-resistance, high-flow network, with blood flow physiology similar to arteriovenous shunts commonly created for hemodialysis access. A mock circulatory loop (MCL) that mimics shunt physiology is an essential tool for refinement and durability testing of arteriovenous implantable bioartificial organs and silicon blood-interfacing membranes. We sought to develop a compact and cost-effective MCL to replicate flow conditions through an arteriovenous shunt and used data from the MCL and swine to inform a bond graph mathematical model of the physical setup. METHODS: Flow physiology through bioartificial organ prototypes was obtained in the MCL and during extracorporeal attachment to swine for biologic comparison. The MCL was tested for stability overtime by measuring pressurewave variability over a 48-h period. Data obtained in vitro and extracorporeally informed creation of a bond graph model of the MCL. RESULTS: The arteriovenous MCL was a cost-effective, portable system that reproduced flow rates and pressures consistent with a pulsatile arteriovenous shunt as measured in swine. MCL performance was stable over prolonged use, providing a cost-effective simulator for enhanced testing of peripherally implanted bioartificial organ prototypes. The corresponding bond graph model recapitulates MCL and animal physiology, offering a tool for further refinement of the MCL system.

Characterization of human islet function in a convection-driven intravascular bioartificial pancreas.

Clinical islet transplantation for treatment of type 1 diabetes (T1D) is limited by the shortage of pancreas donors and need for lifelong immunosuppressive therapy. A convection-driven intravascular bioartificial pancreas (iBAP) based on highly permeable, yet immunologically protective, silicon nanopore membranes (SNM) holds promise to sustain islet function without the need for immunosuppressants. Here, we investigate short-term functionality of encapsulated human islets in an iBAP prototype. Using the finite element method (FEM), we calculated predicted oxygen profiles within islet scaffolds at normalized perifusion rates of 14-200 nl/min/IEQ. The modeling showed the need for minimum in vitro and in vivo islet perifusion rates of 28 and 100 nl/min/IEQ, respectively to support metabolic insulin production requirements in the iBAP. In vitro glucose-stimulated insulin secretion (GSIS) profiles revealed a first-phase response time of <15 min and comparable insulin production rates to standard perifusion systems (~10 pg/min/IEQ) for perifusion rates of 100-200 nl/min/IEQ. An intravenous glucose tolerance test (IVGTT), performed at a perifusion rate of 100-170 nl/min/IEQ in a non-diabetic pig, demonstrated a clinically relevant C-peptide production rate (1.0-2.8 pg/min/IEQ) with a response time of <5 min.